Chapter 27 Bacterial Infections (2024)

KEY TERMS AND DEFINITIONS

Antibiotic

a substance that kills or inhibits the growth of bacteria.

Bacteria

unicellular (single-celled) microorganisms. The singular of this term is bacterium.

Bactericidal

able to kill bacteria.

Bacteriostatic

suppressing the growth of bacteria.

Broad-spectrum

a term describing an agent that has activity against a wide variety of microorganisms.

Infection

invasion by pathogenic microorganisms, which multiply in a host.

Microorganism

a life form of microscopic size (not visible to the unaided eye).

Normal flora

microorganisms inhabiting the human body that under normal circ*mstances do not cause illness or disease.

Nosocomial

acquired in or associated with a healthcare facility.

Pathogen

organism that causes illness or disease.

Prophylaxis

prevention of illness or disease. (adjective = Prophylactic).

Resistance

the ability of microorganisms to withstand the effects of antibiotics.

LEARNING OBJECTIVES

After completing this chapter, you should be able to

  1. Define:

    • Infection

    • Bacteria

    • Normal flora

    • Pathogen

    • Resistance

  2. Outline the concept of normal flora bacteria and the mechanism behind the development of pathogenicity.

  3. Describe host defense mechanisms.

  4. Recognize the types of bacteria and bacterial infections.

  5. Explain the therapeutic effects of antibiotics and the most common indications for each class.

  6. Identify factors relevant to antibiotic selection.

  7. Outline the management of patients with bacterial infections, including monitoring for efficacy and safety.

Bacteria are single-celled microscopic organisms that live in soil, water, and humans. Bacteria are found everywhere on earth and in all types of environments. There are approximately five nonillion (5 × 1030) bacteria on earth.1

In humans, bacteria reside on the skin and in the digestive tract, genitourinary tract, airways, and mouth. When these bacteria stay in a particular part of the body and do not cause harm or infection, they are referred to as normal flora or colonizing bacteria. Normal flora protects the body against disease-causing organisms. Normal flora also performs tasks that are useful to the human host. Skin flora prevents pathogenic organisms from colonizing the surface of the skin by utilizing nutrients for themselves and/or being hostile to pathogenic organisms. The flora that resides in the gastrointestinal (GI) tract are often referred to as gut flora. These organisms are responsible for many functions, such as preventing the overgrowth of pathogenic organisms, carbohydrate metabolism, production of certain vitamins (biotin, vitamin K), and various other functions. It is important to understand that not all bacteria are infectious when they reside in their normal environment and that they perform many important functions.

CASE STUDY

G. F. is a 16-year-old male who presents to the emergency room (ER) with shortness of breath and increased sputum production. G. F. states he has not felt well for the past couple of days but today has trouble breathing. Upon examination in the ER, breath sounds are positive for wheezing with crackles, temperature 102.1°F, oxygen saturation 89%, and white blood cell (WBC) count = 15.7 (normal WBC count = 4–10). Blood and sputum cultures are obtained and sent to the laboratory for analysis.

Bacteria that cause illness or disease are known as pathogens; they are referred to as pathogenic. Bacteria become pathogenic when they produce toxins and/or gain access to a body location where they are not tolerated as normal flora. Toxin production or invasion by pathogenic organisms are considered infection. Many host factors may influence the likelihood of infection. Host defense mechanisms can be classified as natural barriers, nonspecific immune responses, and specific immune responses.

Natural barriers to infection include the skin, mucous membranes, respiratory tract, and GI tract. The skin usually provides protection unless its barrier is physically disrupted (eg, injury, abrasion, incision, burns, or intravenous catheter). Mucous membrane barriers include secretions that are produced by the body (eg, cervical mucus, tears, or saliva). Many of these secretions contain immunoglobulins, which are proteins that are used by the immune system to identify and neutralize foreign substances, such as IgA and IgG that prevent organisms from attaching to host cells. The respiratory tract barrier consists of cilia (short hair-like structures that extend from a cell and move in locomotion). The lining of the respiratory tract serves as a filter mechanism as it transports invading organisms away from the lung. In addition, coughing serves as a barrier to remove these organisms. GI barriers include the acidic content of the GI tract and antibacterial activity of pancreatic enzymes, bile, and secretions released by the intestine. As mentioned earlier, the normal flora of the GI tract can serve as a barrier because they inhibit pathogenic organisms by competing for environmental resources.

Once a pathogenic organism is recognized, the body’s natural defenses are initiated. Nonspecific immune responses are usually produced first. This response involves fever and the increased production of neutrophils, WBCs capable of ingesting microorganisms or particles (discussed in Chapter 25). The inflammation that occurs during an infection directs the immune system response to the site of injury or infection by increasing blood flow to that site and increasing vascular permeability. This allows the WBCs to penetrate tissues and access the site to begin inhibiting the spread of the infectious organism.

Specific immune responses occur after infection. The body produces antibodies and immunoglobulins that adhere to specific targets on the infecting organisms. The antibodies help cells ingest antigens, inactivate toxic substances that are produced by bacteria, and attack bacteria directly. In addition, the specific immune response activates systems responsible for clearing pathogens from a host.

When there are breakdowns or deficiencies in the body’s defense system, the host is vulnerable to many types of infections. Defects in natural barriers include impaired cough, loss of gastric acidity, loss of cutaneous (skin tissue) integrity, and loss of normal flora. Defects in immune barriers, which include disease states that limit or inhibit the production or replication of the body’s immune cells, are referred to as immunosuppression or immunodeficiency. Diseases, such as HIV infection, lupus, leukemia, and megaloblastic anemia, and decreases in numbers of WBCs lead to immunosuppression. Additionally, certain medications can contribute to deficiencies in the host’s immune response. These medication classes include some cancer chemotherapies, some biologics, and corticosteroids.

Signs and Symptoms of Bacterial Infections

Signs and symptoms in the infected host are based on the location and the type of infection. Infection can be confirmed by fever, other signs and symptoms, and predisposing factors. Fever is defined as a controlled elevation of body temperature above the normal range of 36°C to 37.8°C (98.2°F to 99.5°F). The increase in body temperature is a defense mechanism. Some organisms are susceptible to moderate temperature elevations and, in addition, the elevation of temperature activates many of the body’s other defense mechanisms. Recall from Chapter 25 that certain WBCs are responsible for providing defense against invading pathogens. Most infections cause an elevation of the body’s WBC count, known as leukocytosis.

PRACTICE POINT

Not all infections result in an increase in WBC count.

Identification of the pathogen assists with confirming the presence of infection. Infected body materials are often sampled for this purpose. Such sampling is known as culturing. It is most effective if cultures are obtained prior to antibiotic therapy.

CASE?

What signs and symptoms of infection does G. F. have?

PRACTICE POINT

If cultures are obtained after antibiotics are started, the sample may reveal a false-negative culture or altered cellular and chemical composition of the infected sample, as a result of the antibiotic’s action.

Several types of cultures can be obtained from the infected host. These include blood, sputum, tissue, wound, urine, stool, cerebral spinal fluid, and samples from other body fluids. The interpretation of the culture is important in determining whether the organisms identified (if any) are pathogenic, contaminant, or normal flora from the site of collection. Another test used to assist in obtaining useful information regarding the type of organism present is known as a Gram stain. Gram staining rapidly classifies bacteria into broad groups based on their shape and color and may provide useful information to assist in the initial selection of antibiotic therapy before culture results are completed.

For certain types of infections, such as pneumonia, other methods can be used to diagnose or confirm the presence of infection. This includes chest x-rays to review the patient’s lungs for images that may reveal infiltration in the lobes of the lung. Computed tomography (CT) scans along with magnetic resonance imaging (MRI) can allow the clinician a better view of infectious processes in many parts of the body.

There are many different types of infections that occur in humans. Bacterial infections can form in every system of the human body. Table 27-1 classifies various types of infections, location, and some of the most common signs and symptoms.

TABLE 27-1.

Signs and Symptoms of Bacterial Infections

Type of Infection

Location

Signs and Symptoms

Meningitis

Central nervous system

Fever, stiffness of neck and back, altered mental status, headache

Brain and meningeal abscess

Central nervous system

Fever, altered mental status

Encephalitis

Central nervous system

Fever, altered mental status

Sinusitis (sinus infection)

Respiratory (upper)

Fever, nasal discharge, facial pain

Otitis media (ear infection)

Respiratory (upper)

Fever, irritability, discharge

Pneumonia

Respiratory (lower)

Fever, chills, shortness of breath, productive cough

Bronchitis

Respiratory (lower)

Persistent cough, malaise

Enteritis

Gastrointestinal tract

Fever, diarrhea, dehydration

Peritonitis

Intra-abdominal

Fever, nausea, vomiting, abdominal guarding

Bacteremia

Blood

Fever, chills, malaise

Cellulitis

Skin/soft tissue

Edema, erythema, fever

Gonorrhea

GU tract

Dysuria, urethritis, discharge

Urinary tract infection (UTI)

GU tract

Dysuria, urgency, frequency

CASE?

What organisms are the most likely cause of G. F.’s infection?

Classification of Bacteria

There are several types of bacteria that are responsible for causing infections. The classification of bacteria includes the association of bacteria into an organized form of naming referred to as taxonomy. This includes the genus and species names of the bacteria. For example, with the bacterium known as Staphylococcus aureus, Staphylococcus is the genus or family name and aureus is the specific species. In addition, bacteria are classified by their shapes, known as morphology. There are three basic morphologies of bacteria: round (coccus), rod-shaped (bacillus), or spiral-shaped (spirillum). Bacteria are also classified by their color after a stain is applied. This staining process is referred to as a Gram stain. As mentioned previously, Gram staining is an empirical method of differentiating between the main groups of bacteria: Gram positive, Gram negative, and acid fast. Gram-positive bacteria have a thick cell wall that stains purple. Gram-negative bacteria have a thin cell wall that stains pink. Acid-fast bacteria resist Gram staining because the cell walls contain a high concentration of lipids. Finally, bacteria can be classified based on oxygen requirements. Those bacteria that require oxygen to live and grow are referred to as aerobic and those not needing oxygen are referred to as anaerobic.

The two most common groups of Gram-positive cocci (round) are staphylococci and streptococci. These are the genus names and there are several species within each group. When viewed microscopically, staphylococci appear in clumps (clusters) like a bunch of grapes and streptococci form chains. The most common pathogen in the Staphylococcus group is Staphylococcus aureus. Further tests can differentiate Staphylococcus aureus from other staphylococci. All species of staphylococci are normal flora and colonize on the skin and mucous membranes of humans.

Streptococci are classified according to their ability to break down blood in fresh blood agar plates. Some streptococci have no effect on blood and are termed nonhemolytic streptococci. The most important of the nonhemolytic streptococci are the enterococci, such as Enterococcus faecalis and Enterococcus faecium, both of which are normal flora in the GI tract. Other streptococci cause partial breakdown of blood and are called alpha-hemolytic streptococci, which are often referred to as viridans (green) streptococci. The viridans streptococci are a large and heterogeneous group of bacteria and include organisms that play a role in tooth decay and those that can cause endocarditis (infection of the tissue surrounding the heart) and brain abscesses. The most common pathogen of the alpha-hemolytic streptococci family is Streptococcus pneumoniae (the cause of pneumococcal pneumonia and meningitis). The beta-hemolytic streptococci cause the complete breakdown of blood in fresh blood agar plates. Clinically, the most important of the beta-hemolytic streptococci is Streptococcus pyogenes, the infecting organism for strep throat.

The Gram-positive bacilli (rods) can be divided according to their ability to produce spores. Spores of Gram-positive rods are highly resistant structures that may add considerably to their pathogenic capacity. Gram-positive rods that are spore forming are grouped in the genus Bacillus. Important members of this genus include Bacillus anthracis (the cause of anthrax) and Bacillus cereus (a cause of food poisoning). Gram-positive rods that are anaerobic spore formers are grouped in the class clostridia. These include Clostridium perfringens, a principal cause of gangrene, Clostridium tetani (the cause of tetanus), Clostridium botulinum (the cause of the fatal food poisoning botulism), and Clostridioides difficile (C. diff), a growing cause of infectious diarrhea following antibiotic therapy.

The non-spore-forming Gram-positive rods include coryneform bacteria and lactobacilli. Some lactobacilli are important members of the normal vagin*l flora of women of child-bearing age. A common pathogen of this group includes Listeria monocytogenes, which is one of the most virulent foodborne pathogens. Table 27-2 organizes the Gram-positive bacteria by shape, oxygen use (ie, aerobic or anaerobic), and enzyme-producing groups.

TABLE 27-2.

Classification of Common Gram-Positive Microorganisms

Aerobic Gram Positive

Cocci

Streptococci: Streptococcus pneumoniae, Streptococcus viridans

Enterococci: Enterococcus faecalis, Enterococcus faecium

Staphylococci: Staphylococcus aureus, Staphylococcus epidermidis

Bacilli (rods)

Corynebacterium

Listeria

Anaerobic Gram Positive

Cocci

Peptococcus

Peptostreptococcus

Bacilli (rods)

Clostridia: Clostridium perfringens, Clostridium tetani, Clostridioides difficile

Propionibacterium

The Gram-negative bacteria have an outer thin cell wall and stain pink on a Gram stain. The Gram-negative cocci include the genera Moraxella and Neisseria.2 The most pathogenic Neisseria organisms include Neisseria meningitidis (the cause of bacterial meningitis) and Neisseria gonorrhoeae (the cause of gonorrhea). These organisms are most often seen in pairs and are commonly referred to as diplococci.

Gram-negative bacilli include the order enterobacterales. This group is differentiated into types based on whether they can grow in the presence (aerobic) or absence (anaerobic) of oxygen and are frequently found in the GI tract of humans and animals. Some pathogens in this group include Yersinia pestis (the cause of plague), Salmonella typhi (the cause of typhoid), Shigella dysenteriae (the cause of bacillary dysentery), Pseudomonas aeruginosa (the cause of many types of infections associated with high mortality rates), and Salmonella enteritidis (the cause of food poisoning). Additional members of this class include Escherichia coli and members of the genus Klebsiella. The Vibrio and Campylobacters are Gram-negative rods that appear curved or spiral in shape. These bacteria are commonly found in natural waters, both freshwater and marine. Vibrio cholerae (the cause of the waterborne infection cholera), Campylobacters (the cause of bacterial enteritis), and Helicobacter pylori (the cause of stomach ulcers) are common pathogens in this group.

Some Gram-negative bacilli appear so short that they often resemble cocci under the microscope. These are sometimes referred to as cocco-bacilli. This group includes members of the genera Haemophilus and Acinetobacter, the latter being a cause of hospital-acquired (nosocomial) infections. Other Gram-negative bacteria are very fastidious (specific) in their nutritional requirements, including members of the genus Legionella, which cause atypical pneumonias and Legionnaires’ disease. Anaerobic Gram-negative bacilli include the genus Bacteroides, which causes infections of the peritoneal (abdominal) cavity and GI tract, and Fusobacteria, which causes periodontal (gum) infections. Table 27-3 organizes the Gram-negative bacteria by shape, oxygen use, and enzyme-producing groups.

TABLE 27-3.

Classification of Common Gram-Negative Microorganisms

Aerobic Gram Negative

Cocci

Neisseria: Neisseria meningitidis, Neisseria gonorrhoeae

Moraxella catarrhalis

Bacilli (rods)

Enterobacterales: Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Proteus, Serratia, Salmonella, Shigella

Pseudomonas

Legionella

Helicobacter pylori

Cocco-bacilli

Haemophilus

Anaerobic Gram Negative

Cocci

Veillonella

Bacilli (rods)

Bacteroides: Bacteroides fragilis

Fusobacterium

Prevotella

The next group of bacteria includes the acid-fast bacteria, which possess a waxy cell wall, and they rarely stain using the basic Gram stain technique. These bacteria are identified using a different technique of staining that requires acid and alcohol. The most pathogenic organisms in this group include Mycobacterium tuberculosis, which causes tuberculosis, and Mycobacterium leprae, which causes leprosy.

A final group of bacteria is referred to as atypical. They are smaller in size than normal bacteria. The most common pathogenic forms are those in the Mycoplasma, Chlamydia, and Rickettsia groups. Mycoplasma lack cell walls and are highly pleomorphic, meaning they can change shape. The most common pathogen is Mycoplasma pneumoniae, which can cause both upper and lower respiratory infections, including tracheobronchitis and atypical pneumonia. Members of the genus Chlamydia have cell walls and are coccoid in shape. The most common pathogen in this group is Chlamydia trachomatis, a cause of female reproductive problems, pelvic inflammatory disease (PID), and neonatal respiratory and eye infections. The rickettsiae appear as pleomorphic (form-changing) bacillary or coccobacillary (short rod or oval) forms. The most common pathogens in this group include Rickettsia rickettsii, the cause of Rocky Mountain spotted fever (transmitted by ticks), and Rickettsia prowazekii, the cause of epidemic typhus fever (transmitted by infected human body lice).

Bacterial Resistance

When antibiotics first came into use in the 1930s, they were effective against most bacterial infections. Over time, many antibiotics have lost effectiveness against common bacterial infections due to the increase of antibiotic resistance. Bacteria may be naturally resistant to different classes of antibiotics or may acquire resistance from other bacteria through the exchange of resistant genes. Bacteria can be resistant to antibiotics in many ways. There are four main mechanisms by which bacteria exhibit resistance to antibiotics:

  1. Inactivation or modification of the antibiotic—Bacteria produce enzymes that deactivate the antibiotic (eg, bacteria produce an enzyme called beta-lactamase that inactivates penicillins).

  2. Alteration of the target site for the antibiotic—For example, penicillin binds to penicillin-binding protein (PBP) on some bacteria, but certain bacteria have altered this protein and the antibiotic cannot bind to the organism.

  3. Alteration of metabolic pathways—For example, sulfonamide antibiotics work by disrupting the synthesis of folic acid by altering para-aminobenzoic acid (PABA). Some sulfonamide-resistant bacteria are able to utilize preformed folic acid and are not dependent on PABA for folic acid synthesis.

  4. Reduction of drug transport across the cell wall—This occurs by genetic alterations in certain bacteria that decrease the permeability of the cell wall to the drug or increases active efflux (pumping out) of the antibiotic across the surface of the cell.

Susceptibility

Susceptibility refers to the sensitivity of a microorganism to a given antibiotic. Susceptibility testing is often used to determine the likelihood that a particular antibiotic regimen will be effective in eliminating or inhibiting the infection. Susceptibility testing is performed by growing the bacterial isolate in the presence of varying concentrations of several antimicrobials and then examining the amount of growth to determine which concentrations of antimicrobials inhibit the growth of the bacteria. Results are reported as susceptible (likely to inhibit the pathogenic microorganism), intermediate (may be effective at a higher-than-normal concentration), and resistant (not effective at inhibiting the growth of the organism). The organism is categorized as susceptible, intermediate, or resistant by determining the minimum inhibitory concentration (MIC) of the antibiotic. The MIC is the lowest concentration of an antibiotic that inhibits the growth of the bacteria. This information is then used to determine the best option for treating the infection. While broad-spectrum antibiotics are often ordered as initial therapy (to begin treatment of an apparent infection before all tests are complete), prolonged or inappropriate use of such agents can lead to antibiotic resistance, and more specific therapy is generally prescribed once the susceptibility of the infecting organisms has been determined.

PRACTICE POINT

Once the organism is identified and antibiotic sensitivities are known, antibiotic therapy should be changed, if necessary, to the narrowest-spectrum agent that will treat the infection. This way we can prevent antibiotic resistance and unnecessary side effects caused by broad-spectrum antibiotics. This is why antibiotic orders are sometimes revised after a few days of treatment.

Antibiotic Medications

Antibiotics are the drugs of choice for the treatment of bacterial infections. The goal of antibiotic therapy is to kill invading bacteria without harming the host. Antibiotic effectiveness depends on the mechanism of action of the antibiotic, distribution of the drug to the site of infection, immune status of the host, and resistance patterns of the organism.

The first class of antibiotics discussed here are those that are categorized in the beta-lactam group (because they have a beta-lactam ring in their chemical structure). Beta-lactam antibiotics work by inhibiting cell wall synthesis of bacteria. The first antibiotic class in this group to be discovered was penicillin. It was discovered by Alexander Fleming in 1928 and developed as a treatment for human infections in the late 1930s.3 Over the years, as a result of research prompted by bacterial resistance, the beta-lactam class has grown into several groups with various spectra of activity (ie, activity against specific types of microorganisms).

Penicillins are bactericidal. They kill bacteria by activating enzymes that destroy the bacterial cell wall.3 Some organisms produce beta-lactamase, an enzyme that inactivates penicillins. This effect can be blocked by adding a beta-lactamase inhibitor (clavulanic acid, sulbactam, or tazobactam) to the penicillin. Penicillins are primarily used for Gram-positive organisms and some Gram-negative cocci. A minority of Gram-negative bacilli are also susceptible to large parenteral (intravenous, or IV) doses of penicillin.

All classes of penicillins have the same adverse effects and reaction, which include anaphylaxis, drug-fever, serum sickness, rash, nephritis, hemolytic anemia, and leucopenia. Side effects patients may experience when taking these medications include diarrhea, colitis, nausea, and vomiting. Most of the penicillins are renally excreted and dose modifications are necessary for patients with impaired kidney function. The lists that follow detail the characteristics of the major groups of penicillin antibiotics. Pronunciations, brand names, and dosage forms for these agents are detailed in Medication Table 27-1 (Medication Tables are located at the end of the chapter).

PRACTICE POINT

Human cells do not have cell walls, so they are not susceptible to the cell wall destructive action of beta-lactam antibiotics on the walled bacterial cells.

ALERT!

Penicillin G for injection is available in different salts (benzathine, potassium, and procaine), which are not interchangeable. Of these, only penicillin G potassium solution may be administered via the IV route; the others are long-acting suspensions for intramuscular (IM) injection.

Natural Penicillins

    Penicillin G (IV) Penicillin VK (Oral) Penicillin benzathine/procaine (IM)

  • Spectrum of activity

    • Gram-positive organisms (e.g., streptococci)

    • Gram-negative organisms (Neisseria meningitides)

  • Avoid use for staphylococci infections

  • Advantages: good oral absorption; inexpensive; IM formulation utilized for syphilis, as well as some respiratory tract infections and antibacterial prophylaxis in patients with rheumatic heart disease

  • Disadvantages: frequent dosing (q 4 hr to q 6 hr) for oral and IV dosage forms; increasing resistance

Aminopenicillins

Ampicillin (IV, Oral) Amoxicillin (Oral)

    Ampicillin/Sulbactam (IV) Amoxicillin/Clavulanate (PO)

  • Semisynthetic (chemically altered) derivatives of natural penicillins

  • Are not susceptible to acid hydrolysis in the digestive tract (unlike natural penicillins)

  • Spectrum of activity

    • Gram-positive organisms (enterococci, streptococci, Listeria)

    • Gram-negative organisms (better activity compared with natural penicillins)

  • Ampicillin/sulbactam and amoxicillin/clavulanate include beta-lactamase inhibitors, which increases the spectrum of activity, including coverage against anaerobic bacteria

  • Advantages: broader spectrum than natural penicillins; good tissue distribution

  • Disadvantages: superinfections (an infection following a previously treated infection, typically caused by an overgrowth of bacteria that were not affected by antibiotic therapy treating the initial infection); GI intolerance more commonly seen with oral formulations that contain a beta-lactamase inhibitor.

PRACTICE POINT

Aminopenicillins for IV use are not compatible with all commonly used admixture solutions and are most frequently mixed in normal saline (0.9% sodium chloride) for maximum stability. Technicians should review package inserts and reference materials before reconstitution and admixture.Oral ampicillin has poor absorption, causing increased GI side effects. Amoxicillin is preferred for oral therapy.

ALERT!

Amoxicillin is available with and without clavulanate in many oral dosage forms, including capsules, chewable tablets, extended-release tablets, and powders for suspension, and in a wide variety of strengths. With so many choices, extra care must be taken to select the correct product for dispensing.

Antistaphylococcal (Penicillinase-Resistant) Penicillins

    Nafcillin (IV) Oxacillin (IV) Dicloxacillin (PO)

  • Have activity against organisms (Staphylococcus) that produce beta-lactamase (penicillinase), which inactivates natural penicillins (no need for added beta-lactamase inhibitor)

  • Spectrum of activity

    • Gram-positive organisms, staphylococci (main target)

  • No Gram-negative activity

  • Advantages: preferred agents for methicillin-susceptible Staphylococcus aureus (MSSA); no dosing adjustment needed for renal function impairment

  • Disadvantages: frequent dosing (q 4 hr); no activity against methicillin-resistant Staphylococcus aureus (MRSA) or Gram-negative organisms

Extended-Spectrum Penicillins

    Piperacillin/Tazobactam (IV)

  • Activity against organisms that produce beta-lactamase, which inactivates penicillin (penicillinase)

  • Spectrum of activity

    • Gram-positive organisms (streptococci, enterococci, staphylococci)

    • Gram-negative organisms; adds coverage to more resistant bacteria, including Pseudomonas

    • Anaerobic activity, including Bacteroides fragilis

  • Advantages: broad spectrum of coverage, including Pseudomonas; good tissue distribution

  • Disadvantages: formulations contain large amounts of sodium, may contribute to renal impairment

CASE?

The ER physician orders a 10-day course of ceftriaxone (Rocephin) and azithromycin (Zithromax) intravenously and admits the patient to the medical floor for community-acquired pneumonia. What additional information will the pharmacist want to know about G. F. before these medications are sent for him?

The next group of beta-lactam antibiotics is the cephalosporins, which are bactericidal, with both Gram-positive and Gram-negative activity. Like the penicillins, they inhibit cell wall synthesis. Cephalosporins penetrate well into most body fluids, especially in the presence of inflammation. Hypersensitivity reactions are the most common adverse effect of cephalosporins (urticaria and anaphylaxis are rare). Since the cephalosporins have a beta-lactam ring in the chemical structure like penicillins, some patients who have had an allergic reaction to penicillin may also react to a cephalosporin. Cross-reactivity rates between cephalosporins and penicillins is uncommon and is around 2% to 5%.4 Cephalosporins can be given cautiously to patients with a history of delayed hypersensitivity to penicillin if necessary, but a different class of antibiotics is usually chosen if possible.

Many patients complain of pain with IM injections. Thrombophlebitis (inflammation of the vein) after IV use is possible. Most of the cephalosporins are renally excreted and dose modifications are required for patients with impaired kidney function. All cephalosporins can produce leukopenia and thrombocytopenia and prolonged use can contribute to the development of Clostridioides difficile (pseudomembranous) colitis. The cephalosporins are classified in generations, numbered first through fifth. Later generations generally have an expanded spectrum against aerobic Gram-negative bacilli. The lists that follow detail the characteristics of each generation; additional details are summarized in Medication Table 27-2.

ALERT!

Cephalosporins should not be administered to patients who have had an anaphylactic (life-threatening) reaction to penicillin. If the patient’s allergic reaction to penicillin was considered minor (rash, fever), the cephalosporin is often administered or prescribed anyway. That is why information about the nature of a patient’s allergic reaction is kept in the profile.

First-Generation Cephalosporins

    Cefazolin (IV) Cefadroxil (Oral) Cephalexin (Oral)

  • Spectrum of activity

    • Gram-positive organisms (staphylococci, streptococci)

    • Gram-negative organisms (E. coli, Proteus, Klebsiella)

  • Commonly used for surgical prophylaxis

  • Advantages: inexpensive, good Gram-positive coverage, especially methicillin-susceptible Staphylococcus aureus (MSSA)

  • Disadvantages: little Gram-negative coverage, no Enterococcus coverage

ALERT!

LOOK-ALIKE/SOUND-ALIKE—Both generic names and brand names of many cephalosporins begin with “cef” or “ceph” and are easily confused.

Second-Generation Cephalosporins

    Cefaclor (Oral) Cefuroxime (IV, IM, Oral) Cefprozil (Oral) Cefotetan (IV) Cefoxitin (IV)

  • Often used for polymicrobial infections (multiple microorganisms) involving Gram-negative bacilli and Gram-positive cocci

  • Cefotetan and cefoxitin are referred to as the cephamycins; they have anaerobic activity and are, therefore, mainly used prophylactically for intra-abdominal procedures

  • Advantages: better Gram-negative coverage than the first generations

  • Disadvantages: Increasing resistance; no Enterococcus coverage

ALERT!

LOOK-ALIKE/SOUND-ALIKE—Keflex, a brand name of cephalexin, has been confused with Keppra, an anticonvulsant.

Third-Generation Cephalosporins

    Cefdinir (Oral) Cefditoren (Oral) Cefixime (Oral) Cefotaxime (IV, IM) Cefpodoxime (Oral) Ceftazidime (IV, IM) Ceftibuten (Oral) Ceftriaxone (IV, IM)

  • Spectrum of activity

    • Gram-positive organisms (streptococci)

    • Gram-negative organisms (adds coverage of Neisseria meningitides and H. influenzae)

      • Ceftazidime is the only third-generation cephalosporin with Pseudomonas activity

  • Ceftriaxone and cefotaxime are used empirically (initiation of antibiotic therapy based on the most common organisms that cause the type of infection) for acute meningitis due to suspected Streptococcus pneumoniae, H. influenzae, or Neisseria meningitides

  • Advantages: many therapeutic uses; used to treat nosocomial infections

  • Disadvantages: relatively poor activity against Gram-positive cocci, especially methicillin-sensitive Staphylococcus aureus (MSSA), and no Enterococcus coverage

Fourth-Generation Cephalosporin

    Cefepime (IV, IM)

  • Spectrum of activity

    • Gram-positive organisms; maintains activity against staphylococci and streptococci

    • Gram-negative organisms; adds Pseudomonas activity and beta-lactamase–producing enterobacteriaceae, such as Enterobacter

  • Advantages: broad spectrum of activity

  • Disadvantage: available in IV formulations only, no Enterococcus activity

Fifth-Generation Cephalosporin

    Ceftaroline (IV)

  • Spectrum of activity

    • Gram-positive organism; activity against MRSA

    • Gram-negative organism; similar to third-generation cephalosporins (eg, Ceftriaxone)

  • Advantages: approved for community-acquired pneumonia as well as skin and soft tissue infections

  • Disadvantage: available in IV formulations only, no Enterococcus activity

Cephalosporins with Beta-lactamase Inhibitors

Ceftazidime/Avibactam (IV) Ceftolozane/Tazobactam (IV)

Ceftazidime and Ceftolozane act like other beta-lactams by inhibiting cell wall synthesis. Avibactam and tazobactam have little antibacterial effect but instead inactivate certain enzymes, allowing for a broader spectrum of coverage. Ceftazidime/avibactam and Ceftolozane/tazobactam are utilized for complicated urinary tract infections (UTIs) and, with the addition of metronidazole, complicated intra-abdominal infections.

Ceftazidime/avibactam has activity against both carbapenem-resistant organisms and Pseudomonas aeruginosa. Ceftolozane/tazobactam also has activity against resistant Gram-negative bacteria and is used most commonly for resistant Pseudomonas aeruginosa.

  • Advantages: Good tissue distribution, activity against resistant Gram-negative bacteria

  • Disadvantages: Expensive; dosage may need to be adjusted for patients with impaired renal function

Cefiderocol (IV)

The newest of the cephalosporins, approved for community-acquired UTIs, as well as hospital-acquired/ventilator-associated pneumonia (HAP/VAP). Known to have good Gram-negative activity against more carbapenem-resistant organisms, along with Pseudomonas and Acinetobacter.

  • Advantages: Activity against resistant Gram-negative bacteria

  • Disadvantages: There is an increase in all cause mortality in patients with carbapenem-resistant Gram negative bacterial infections

Other Beta-Lactam Antibiotics

Penicillins and cephalosporins are not the only antibiotics with a beta-lactam ring incorporated into their chemical structures. Carbapenems and monobactams also have this ring and work by inhibiting bacterial wall synthesis. They differ in spectrum of action, effectiveness, and side effect profiles and are included in the beta-lactam summary in Medication Table 27-2.

Carbapenems

Imipenem-Cilastin (IV) Meropenem (IV) Ertapenem (IV, IM) Doripenem (IV)

The carbapenems are bactericidal drugs that have an extremely broad spectrum of activity. All the carbapenems can cause GI disorders, rash, phlebitis, and headache. In rare cases they may cause hypotension (decreases in blood pressure). Imipenem-cilastin can also increase seizure risk. Carbapenem doses must be adjusted in patients with impaired kidney function. There is a possible cross-reaction with penicillins and these drugs should therefore be avoided in severe allergies.

  • Spectrum of activity

    • Gram-positive organisms; broad coverage including enterococci, except ertapenem

    • Gram-negative organisms; broad coverage including Pseudomonas, except ertapenem

    • Anaerobic activity

  • Advantages: broad spectrum of activity

  • Disadvantages: more serious adverse reactions than penicillins and cephalosporins

Meropenem/Vaborbactam (IV)

The first carbapenem with a beta-lactamase inhibitor approved by the U.S. Food and Drug Administration (FDA). Vaborbactam inhibits the degradation of meropenem from bacterial enzymes, allowing for activity against carbapenem-resistant enterobacteriaceae (CRE). Meropenem-vaborbactam is approved for UTI, including pyelonephritis. Known for its broad Gram-negative coverage.

ALERT!

LOOK-ALIKE/SOUND-ALIKE—Doribax, the brand name for doripenem, has been confused with Zovirax, an antiviral injection, and Invanz, the brand name for ertapenem, has been mistaken for Avinza, an oral morphine preparation.

Imipenem-Cilastin-Relebactam (IV)

This is the newest carbapenem with a beta-lactamase inhibitor. The purpose of relebactam is to restore the activity of resistant organisms to imipenem-cilastin. This includes carbapenem-resistant Klebsiella and Pseudomonas. Imipenem-cilastin-relebactam is approved for complicated UTIs and intra-abdominal infections.

Monobactams

Aztreonam (IV, IM, Inhalation)

The monobactams are cell wall–inhibiting bactericidals. They can cause similar side effects to carbapenems and must be dose-adjusted in patients with impaired kidney function. The only agent in this group currently available in the United States is aztreonam and this antibiotic only has Gram-negative activity, including Pseudomonas.

  • Advantages: excellent safety profile; can be used safely in penicillin-allergic patients

  • Disadvantages: no Gram-positive or anaerobic coverage, increasing resistance in Pseudomonas sp.

Non-Beta-Lactam Antibiotics

Fluoroquinolones

Levofloxacin (IV, Oral) Ciprofloxacin (IV, Oral, Otic, Ophthalmic) Moxifloxacin (IV, Oral) Ofloxacin (Oral, Otic, Ophthalmic) Delafloxacin (IV, Oral)

The fluoroquinolones (often called quinolones for short) are bactericidal and act by inhibiting the activity of enzymes essential for bacterial DNA replication. Fluoroquinolone doses must be adjusted for patients with impaired kidney function. They can cause nausea, vomiting, and diarrhea, as well as altered mental status and confusion when not properly adjusted for renal function. They can cause cardiac dysfunction in patients with cardiac conduction problems or when used in combination with other medications that have cardiac effects, which can predispose patients to ventricular tachyarrhythmia. Another downside to these antibiotics is the concern for tendon rupture. Characteristics of the fluoroquinolones are listed below; additional details are summarized in Medication Table 27-3.

  • Spectrum of activity

    • Gram-positive organisms; Moxifloxacin and Levofloxacin overall have good activity against streptococci infections

    • Gram-negative organisms; Levofloxacin and Ciprofloxacin have Pseudomonas activity

    • Adds atypical coverage (Mycoplasma spp., Chlamydophilia spp., Mycobacterium)

    • Anaerobic activity with Moxifloxacin (only one in its class)

    • Delafloxacin has activity against Pseudomonas and MRSA (only one in its class)

  • Advantages: convenient dosing (q 12 hr, q 24 hr), good tissue distribution

  • Disadvantages: should not be administered to children younger than 16 years (cartilage dysfunction); some serious side effects

PRACTICE POINT

The oral fluoroquinolones should not be administered at the same time as preparations containing aluminum, calcium, magnesium, and iron, such as antacids or dietary supplements.

Aminoglycosides

Amikacin (IV, IM) Gentamicin (IV, IM, Ophthalmic) Neomycin (Oral) Paromomycin (Oral) Plazomicin (IV) Streptomycin (IV, IM) Tobramycin (IV, IM, Inhalation, Ophthalmic)

The aminoglycosides are bactericidal and work by inhibiting bacterial protein synthesis. Aminoglycosides are poorly absorbed orally and are administered by inhalation, intravenously, topically, and in the eye and ear. Oral dosage forms are indicated only for intestinal infections and for the treatment and prevention of hepatic encephalopathy (see Chapter 23).

The aminoglycosides have a narrow therapeutic range, meaning that, while a minimum concentration is necessary for bactericidal action, at higher concentrations they can cause serious adverse effects. These adverse events include nephrotoxicity (kidney damage), which in most cases is reversible, and ototoxicity (hearing loss/impairment), which is often irreversible. To prevent these adverse events from occurring, clinicians must base the dose of these medications on several pharmaco*kinetic parameters, including patient weight, site of infection, and renal function. Pharmaco*kinetic equations (of the type introduced in Chapter 2) are used to determine the proper dose and dosing interval to achieve therapeutic drug levels, to ensure eradication of the infecting organism without causing harm to the patient. Peak levels are determined within 30–60 minutes after a dose has been administered and are presumed to be the highest blood concentration of antibiotic that is achieved. Trough levels are determined shortly before the next scheduled dose is given and are presumed to be the lowest level to which antibiotic concentrations fall in a specific treatment regimen. Characteristics of the aminoglycosides are listed below; additional details are summarized in Medication Table 27-3.

ALERT!

IV doses of the fluoroquinolones should be infused over at least 60 minutes, regardless of the volume or dose; longer infusion times may be required for higher doses.

ALERT!

LOOK-ALIKE/SOUND-ALIKE—Gentamicin has been involved in medication mix-ups with gentian violet, a topical antiseptic.

  • Spectrum of activity

    • Gram-positive; only in combination with cell wall inhibitors (eg, beta-lactams) for synergy

    • Gram-negative; can be used alone or, for serious infections, in combination with other antibiotics

  • Advantages: excellent Gram-negative coverage; provides synergistic activity for Gram-positive infections

  • Disadvantages: nephrotoxicity, ototoxicity, cost of monitoring when used systemically

PRACTICE POINT

During systemic therapy with aminoglycosides, patient blood samples are sent to the lab to confirm that antibiotic concentrations are within the therapeutic window.

Macrolides

Azithromycin (IV, Oral) Clarithromycin (Oral)

Erythromycin (IV, Oral, Ophthalmic, Topical) Fidaxomicin (Oral)

Unlike the groups discussed above, the macrolide antibiotics are primarily bacteriostatic. They kill bacterial cells by inhibiting protein synthesis and, thus, suppress bacterial replication.

Erythromycin, the prototype macrolide, has peristalsis activity, therefore causing GI disturbances, including nausea, vomiting, abdominal cramps, and diarrhea. These side effects are less common with clarithromycin and azithromycin, which were developed later. Erythromycin may cause dose-related tinnitus (ringing of the ears), dizziness, and reversible hearing loss. Erythromycin has numerous drug interactions because it inhibits hepatic metabolism through the cytochrome P-450 system, so it can increase drug levels of other medications that are metabolized through the same pathway. This interaction can lead to toxic drug levels that predispose patients to adverse drug reactions and side effects. The macrolides can cause cardiac dysfunction in patients with cardiac conduction problems or when used in combination with other medications that have certain cardiac effects. This may then predispose a patient to ventricular tachyarrhythmia. Erythromycin and clarithromycin can further elevate the PT/INR (prothrombin time/international normalized ratio) when taken with warfarin. Azithromycin has the lowest tendency of the macrolides to cause drug interactions. Characteristics of the macrolides are listed below; additional details are summarized in Medication Table 27-3.

  • Spectrum of activity

    • Gram-positive organisms (streptococci)

    • Gram-negative organisms (limited activity)

    • Atypical bacteria: Mycoplasma pneumoniae, Chlamydia trachomatis, Chlamydophila pneumoniae, Legionella sp., Corynebacterium diphtheriae, Campylobacter, Treponema pallidum, Propionibacterium acnes, and Borrelia burgdorferi

    • Clarithromycin is used for Helicobacter pylori

  • Fidaxomicin’s only place in therapy is for Clostridiodes difficile colitis

  • Advantages: good for community-acquired infections, convenient dosing (azithromycin), dosage not adjusted for renal impairment (exception clarithromycin)

  • Disadvantages: high side effect profile; many drug interactions with other medications that have cardiac effects (QT prolongation) and predisposes to ventricular tachyarrhythmia; increased resistance

Tetracyclines

Doxycycline (IV, Oral) Minocycline (IV, Oral) Tetracycline (Oral) Tigecycline (IV) Omadacycline (IV, Oral) Eravacycline (IV)

The tetracyclines are bacteriostatic antibiotics that slow bacterial growth by inhibiting bacterial protein synthesis. Because tetracycline absorption is decreased by metallic cations such as aluminum, calcium, magnesium, and iron, preparations containing these ions should not be taken with this class of antibiotics. All tetracyclines can cause nausea, vomiting, and diarrhea. They can also exacerbate gastroesophageal reflux disease (GERD, discussed in Chapter 20). Tetracyclines can cause photosensitivity (increased incidence of sunburns when exposed to the sun). They can cause staining of teeth, hypoplasia (defects) of dental enamel, and abnormal bone growth in children.

Tigecycline, a derivative of tetracycline designed to overcome bacterial resistance, exhibits activity against community-acquired pneumonia, complicated intra-abdominal infections, and complicated skin and skin structure infections caused by susceptible organisms. This includes MRSA and vancomycin-sensitive Enterococcus faecalis. It is only administered intravenously.

Eravacycline is a fluorocycline that is structurally similar to tigecycline, with slight modifications. It is a newer drug in this class, typically used for complicated intra-abdominal infections. It is typically reserved for use against drug-resistant bacteria. It has activity against vancomycin-resistant Enterococcus (VRE), MRSA, anaerobes, and resistant enterobacterales. It is only administered intravenously.

Omadacycline, a semisynthetic tetracycline derivative, is also a newer drug in this class, with activity against community-acquired pneumonia and complicated skin and skin structure infections by susceptible organisms, including MRSA, Enterococcus faecalis, and Enterobacter. In addition to the intravenous form, it is available as an oral tablet. Patients taking omadacycline by mouth should follow the same precautions mentioned for the older tetracyclines.

PRACTICE POINT

While it penetrates tissues very well, tigecycline cannot be used to treat bloodstream infections because it does not reach high enough concentrations there. It is also very expensive; thus, it is reserved for infections that cannot be treated effectively by other antibiotics.

ALERT!

Because of their interactions with bone and dental enamel, tetracyclines should be avoided after the first trimester of pregnancy and in mothers who are breastfeeding, as well as in children below the age of 8.

Characteristics of the tetracyclines are listed below; additional details are summarized in Medication Table 27-3.

  • Spectrum of activity

    • Gram-positive (community-acquired MRSA coverage)

    • Gram-negative (Neisseria gonorrhea and Helicobacter pylori)

    • Atypical (rickettsia, spirochetes [Treponema pallidum, Borrelia burgdorferi], Vibrio sp., Brucella sp., Bacillus anthracis, Mycoplasma, and Chlamydia)

  • Advantages: activity against community-acquired MRSA; inexpensive, not adjusted for impaired renal function

  • Disadvantages: high side effect profile; increasing resistance

PRACTICE POINT

Patients taking tetracyclines and related agents should avoid direct sunlight as well as tanning beds and use a sunblock of SPF 15 or higher on areas exposed to the sun (including the lips).

Glycopeptides

Vancomycin (IV, Oral) Telavancin (IV) Dalbavancin (IV) Oritavancin (IV)

Glycopeptides are bactericidal antibiotics that inhibit cell wall synthesis. Vancomycin can be associated with ototoxicity and nephrotoxicity if drug concentrations in the body become too high. As with the aminoglycosides, several pharmaco*kinetic parameters must be considered by doctors and pharmacists deciding on dose and frequency of administration. Patients at the highest risk for drug accumulation are the elderly and those with impaired kidney function. The oral formulation of vancomycin is not systemically absorbed and is only effective for treating Clostridioides difficile colitis (a local effect in the GI tract). Vancomycin intended for use in treating systemic infections must be infused intravenously over at least 60 minutes. Telavancin is a synthetic derivative of vancomycin indicated only for skin and skin structure infections by certain Gram-positive cocci. It is administered only by IV infusion, over at least 60 minutes. Dalbavancin and oritavancin, like telavancin, are semisynthetic derivatives. Oritavancin can be given as a single dose, whereas dalbavancin can be given in either one to two doses. Both are indicated for skin and skin structure infections for Gram-positive organisms. Oritavancin is administered only by IV, over at least 3 hours, whereas dalbavancin can be administered over 30 minutes.

PRACTICE POINT

IV vancomycin doses should be limited to concentrations of 5 mg/mL, unless patients are fluid-restricted, and infused at rates not to exceed 10 mg/min.

PRACTICE POINT

The FDA requires distribution of a medication guide to patients receiving telavancin.

ALERT!

Glycopeptides can cause a dangerous reaction termed “red man syndrome” that is characterized by redness, flushing, and itching. This is not an allergic reaction; it occurs when IV infusion of the drug is too rapid. Glycopeptides can still be used but the infusion needs to be slowed down.

  • Spectrum of activity

    • Only covers Gram-positive bacteria

    • Gram-positive cocci (staphylococci including MRSA, streptococci, enterococci) and Gram-positive bacilli

    • Oral vancomycin only used for Clostridioides difficile

  • Advantages: very effective against penicillin and cephalosporin-resistant strains of Gram-positive organisms; vancomycin is the drug of choice for MRSA; dalbavancin and oritavancin only require one or two doses

  • Disadvantages: Vancomycin and telavancin can accumulate in patients with impaired kidney function leading to increased drug concentrations and incidence of toxicity

ALERT!

Vancomycin injection is very irritating and is never administered via the IM route.

Sulfonamides

Co-trimoxazole (IV, Oral) Sulfacetamide (Topical, Ophthalmic) Sulfadiazine (Topical, Oral)

The sulfonamides, sometimes called sulfa drugs or sulfas, were the earliest antibiotics marketed for human therapy.3 First used in 1932, they represented a dramatic change in the way infections were treated. Although the penicillins and newer antibiotics, along with the widespread emergence of bacterial resistance to them, have reduced the importance of this class, several are still in use today.

Sulfonamides are bacteriostatic; they inhibit bacterial replication by interfering with folic acid synthesis in bacteria unable to utilize preformed folate for cellular processes. Since the introduction of sulfonamides, many bacterial strains have acquired the ability to skip the metabolic step blocked by sulfonamides and incorporate absorbed folate into their metabolism, so they have become resistant to these antibiotics.

PRACTICE POINT

Human cells are unable to make their own folic acid and always use preformed folate, characterized as an essential vitamin (see Chapter 24) for their body processes, so sulfonamides are not toxic to them the way they are to bacterial cells.

Sulfonamides were named because their chemical structure includes an altered version of the folic acid precursor PABA (the one used by bacteria to make folic acid) that has a sulfate molecule attached.3 A similar structure is also found in other medications, including thiazide diuretics and some diabetes medications.

ALERT!

Patients who have had a hypersensitivity reaction to a “sulfa” drug, for instance, a sulfonamide antibiotic, are more likely to react adversely to other sulfas, such as thiazide diuretics or sulfonylurea diabetes agents. However, this does not preclude the use of a diuretic.

PRACTICE POINT

A sulfa allergy is not the same as a sulfur allergy. Sulfa refers to the sulfonamide chemical structure found in these antibiotics and some other drugs. Sulfur is a chemical element that is part of many nonsulfa medications and included in many bodily substances.

Co-trimoxazole, a combination of the sulfonamide antibiotic sulfamethoxazole and another agent, trimethoprim (which also interferes with bacterial folic acid production), is the most commonly used sulfa anti-infective. It is active against a wide variety of Gram-positive and Gram-negative organisms and is prescribed for the treatment of bacterial infections of the ears (otitis media), GI tract (travelers’ diarrhea), respiratory system, and urinary tract. Co-trimoxazole has also been found to be an effective prophylaxis and treatment for pneumonia caused by the organism Pneumocystis jiroveci, a fungal infection (PJP) that affects immunosuppressed patients, especially HIV-infected individuals. It appears to be effective against toxoplasmosis, a protozoal parasite, as well. Important to note if giving the IV formulation of sulfamethoxazole/trimethoprim, the weight-based dosing is determined using the trimethoprim component.

PRACTICE POINT

The U.S. Department of Health and Human Services recommends oral co-trimoxazole as the drug of choice for primary prophylaxis of Pneumocystis pneumonia in HIV-infected individuals.2

Other sulfa antibiotics include sulfadiazine (used orally for bacterial infections and topically as silver sulfadiazine, for burns), sulfacetamide (used only for ophthalmic infections), sulfasalazine (used in the management of ulcerative colitis—see Chapter 22), and sulfisoxazole (available in combination with erythromycin for the treatment of ear infections). Facts to remember about sulfonamide antibiotics are listed below; additional information is included in Medication Table 27-3.

ALERT!

LOOK-ALIKE/SOUND-ALIKE—The sulfonamide anti-biotics have similar names, and pharmacy personnel have reported errors that occurred when sulfadiazine was confused with sulfisoxazole.

  • Spectrum of activity

    • Co-trimoxazole, wide range of activity

    • Susceptible enterobacterales

    • Pneumocystis jiroveci pneumonia

    • Toxoplasma gondii

    • Listeria monocytogenes

    • Community-acquired MRSA

    • Stenotrophom*onas maltophilia

  • Advantages: inexpensive; useful for less common bacterial infections

  • Disadvantages: allergic/hypersensitivity reactions; increasing resistance; drug interactions (eg, warfarin); monitor for hyperkalemia

Miscellaneous Antibiotics

A number of antibiotics are not classified in groups and are discussed here as miscellaneous. They are listed below with their most prominent characteristics (see also Medication Table 27-3).

Chloramphenicol (IV)

Like many of the other antibiotics, chloramphenicol exerts its antimicrobial action by inhibiting protein synthesis. It is bacteriostatic for a wide variety of microorganisms but is considered bactericidal for H. influenzae, Neisseria meningitidis, and S. pneumoniae.3 Chloramphenicol is an older antibiotic and resistant strains of some pathogens are common.

Unfortunately, chloramphenicol’s protein synthesis inhibition is not limited to microorganisms.3 Some human cells, particularly those of the blood-forming system, are also affected by its action, and it has been known to cause serious, even fatal, blood disorders. For this reason, use of chloramphenicol is limited to serious infections by pathogens with documented sensitivity to the drug and only when less dangerous drugs cannot be used (because of resistance or patient factors such as allergy).

  • Broad spectrum of activity against a wide variety of organisms

  • Used infrequently in the treatment of typhoid fever, meningitis, Rocky Mountain spotted fever, and anthrax when other drugs cannot be used

  • Advantages: broad spectrum, good penetration of spinal fluid for central nervous system infections such as meningitis

  • Disadvantages: resistant organisms; life-threatening adverse reactions; allergic/hypersensitivity reactions

Clindamycin (IV, Oral, vagin*l, Topical)

Clindamycin is classified as lincosamide, which is bacteriostatic by inhibiting protein synthesis of bacteria.

  • Spectrum of activity

    • Activity against anaerobic organisms (above the diaphragm)

    • Community acquired MRSA infections

  • Advantages: option for patients with severe penicillin allergies; renal function dose adjustments are not necessary

  • Disadvantages: high rate of Clostridioides difficile colitis with use

Daptomycin (IV)

Daptomycin is classified as a lipopeptide that is bactericidal by disrupting multiple aspects of bacterial cell membrane function and inhibition of protein, DNA, and RNA synthesis, which results in bacterial cell death.

  • Spectrum of activity

    • Gram-positive cocci (staphylococci, including MRSA, streptococci, enterococci, including vancomycin-resistant Enterococcus [VRE]) and Gram-positive bacilli

  • Advantages: excellent activity for resistant Gram-positive organisms

  • Disadvantages: expensive; cannot be used for pneumonia due to inactivation by lung surfactant; weekly monitoring of creatinine kinase levels

ALERT!

LOOK-ALIKE/SOUND-ALIKE—Daptomycin has been confused with dactinomycin, a cancer chemotherapy.

Linezolid (IV, Oral)

Linezolid is classified as an oxazolidinone that is bacteriostatic by inhibiting bacterial replication. However, it does display some bactericidal activity against certain bacteria.

  • Spectrum of activity

    • Gram-positive cocci (staphylococci, including MRSA, streptococci, enterococci, including vancomycin-resistant Enterococcus [VRE]) and Gram-positive bacilli

  • Advantages: available in IV and oral formulations; excellent tissue penetration; dose not adjusted for renal function

  • Disadvantages: thrombocytopenia and neuropathies with prolonged use; monoamine oxidase inhibitor drug interactions

ALERT!

LOOK-ALIKE/SOUND-ALIKE—Zyvox, the brand name for linezolid, looks and sounds like Zovirax, a brand-name antiviral agent.

Metronidazole (IV, Oral, Topical, vagin*l)

Metronidazole demonstrates bacteriostatic action by disrupting bacterial DNA structure, resulting in inhibition of protein synthesis.

  • Spectrum of activity

    • Excellent activity against anaerobic bacterial (below the diaphragm) and protozoal infections

  • Advantages: available in IV, oral, and topical formulations; does not require renal function dose adjustments

  • Disadvantages: patients have to avoid alcohol while taking medication due to disulfiram-like reaction (severe nausea and vomiting); drug interactions (eg, warfarin)

ALERT!

LOOK-ALIKE/SOUND-ALIKE—Metronidazole looks and sounds like metformin, an agent for the treatment of diabetes, which has a similar dosing range and some same-strength oral tablets.

Rifaximin

Rifaximin works by inhibiting bacterial RNA synthesis. It is used for travelers’ diarrhea and as an alternative for treatment of Clostridioides difficile-associated diarrhea.

  • Activity against Escherichia coli, Acinetobacter, Bacteroides, Enterobacter cloacae, and various other organisms that reside in the GI tract

  • Advantages: low resistance rates; available in oral formulation

  • Disadvantages: superinfections; not for use in children younger than 12 years

Quinupristin/Dalfopristin (IV)

Quinupristin/dalfopristin is classified as a streptogramin, an antibiotic that is bacteriostatic by inhibiting bacterial protein synthesis.

  • Activity against vancomycin-resistant Enterococcus faecium bacteremia; treatment of complicated skin and skin structure infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes

  • Advantages: good activity against resistant Gram-positive organisms

  • Disadvantages: may cause arthralgias and/or myalgias with use and can cause hyperbilirubinemia

Colistimethate (IV, IM, Inhaled)

Colistimethate has bacteriostatic activity by acting as a cationic detergent, which damages the bacterial cytoplasmic membrane, causing leaking of intracellular substances and cell death.

  • Has activity against resistant strains of Gram-negative bacilli (Pseudomonas aeruginosa, Enterobacter aerogenes, Escherichia coli, and Klebsiella pneumoniae)

  • Advantages: active against resistant organisms; may be used as inhalation therapy to treat lung infections

  • Disadvantages: must be dose adjusted in patients with impaired kidney function

Nitrofurantoin (Oral)

Nitrofurantoin is a bactericidal antibiotic with a unique mechanism of action. It is chemically changed by bacteria to a product that inactivates or alters bacterial ribosomal proteins and other macromolecules, inhibiting energy metabolism and DNA synthesis.

  • Only indicated for urinary tract infections

  • Spectrum of activity

    • Common urinary organisms (eg, E. coli, Klebsiella, Proteus, Enterococcus) if susceptible

  • Advantages: inexpensive

  • Disadvantages: should not be used in patients with impaired renal function; avoid for pyelonephritis

Fosfomycin (Oral)

  • Only indicated for urinary tract infections

  • Spectrum of activity

    • Common urinary organisms (eg, E. coli, Klebsiella, Proteus, Enterococcus) if susceptible

  • Advantages: one-time dose

  • Disadvantages: avoid for pyelonephritis

Antimycobacterials/Antituberculosis Antibiotics

These agents are used in the treatment of tuberculosis and other infections caused by the organisms from the genus Mycobacterium. Because the mycobacteria are slow-growing organisms, tuberculosis infection may be active or latent (not causing signs and symptoms of active infection) in the host. At any time, the latent infection can develop into an active disease. The treatment of these infections is complex due to the multidrug-resistant strains of Mycobacterium. Many of the antibiotics used to treat these infections have severe side effects and patient compliance or adherence to treatment regimens is often poor. This has led to bacterial resistance and the need for multiple medication combinations to overcome resistance patterns. A single drug may be given for 4–6 months upon discovery of a latent infection without symptoms, but treatment of active disease usually involves a regimen of two to four drugs, chosen based on the tested sensitivity of the infecting organism.2 Treatment with these drug combinations can range from 18 weeks up to 18 months.

Rifampin (IV, Oral)

Rifampin is a bactericidal antibiotic that inhibits bacterial RNA synthesis by preventing attachment of an enzyme to DNA, thus blocking initiation of RNA transcription.

  • Activity against tuberculosis in combination with other agents; also has activity against Haemophilus influenzae, Legionella pneumonia; used in combination with other anti-infectives in the treatment of staphylococcal and M. leprae infections

  • Disadvantages/considerations: may permanently discolor soft contact lenses; causes red–orange discoloration of urine, feces, saliva, sweat, and tears. There is an increase in bacterial resistance; multiple drug interactions; hepatic dysfunction

ALERT!

LOOK-ALIKE/SOUND-ALIKE—Rifampin looks and sounds like rifaximin, an antibiotic that is not indicated for the treatment of tuberculosis.

Ethambutol (Oral)

Ethambutol is a bacteriostatic antibiotic that interferes with cellular metabolism, resulting in the impairment of bacteria replication and cell death.

  • Used in combination with other antibiotics to treat tuberculosis; has activity against Mycobacterium avium complex (MAC) and Mycobacterium tuberculosis

  • Disadvantages: many side effects, including optic neuritis with decreased visual acuity, dermatitis, pruritus, headache, fever, and mental confusion

Cycloserine (Oral)

Cycloserine may be bactericidal or bacteriostatic, depending on its concentration at the site of infection and the susceptibility of the organism. It interferes with bacterial cell wall synthesis.

  • Used in combination with other antibiotics to treat tuberculosis; has activity against strains of E. coli and Enterobacter for the treatment of urinary tract infections

  • Disadvantages: many side effects, including drowsiness, somnolence, headache, dizziness, anxiety, nervousness, vertigo, and confusion; dose must be adjusted in patients with altered kidney function

Isoniazid (IM, Oral)

Isoniazid is a bactericidal antibiotic with activity against many types of mycobacteria, primarily those that are actively dividing. Its exact mechanism of action is not known, but it may be related to the inhibition of mycolic acid synthesis and disruption of the cell wall.

  • Used in monotherapy or in combination with other antibiotics to treat tuberculosis, as well as in the treatment of both latent and active tuberculosis; has activity against Mycobacterium bovis, M. tuberculosis, and M. kansasii

  • Disadvantages: many side effects; U.S. Black Box Warning: severe and sometimes fatal hepatitis may occur, usually within the first 3 months of treatment, although may develop even after many months of treatment; peripheral neuropathies (tingling, numbness in toes/fingers); vitamin B6 depletion

Pyrazinamide (Oral)

Pyrazinamide may be bacteriostatic or bactericidal, depending on its concentration and the susceptibility of the organism. The exact mechanism of action is unknown but is partially related to the conversion of medication to pyrazinoic acid, which lowers the pH of the environment, leading to the suppression of bacterial growth.

  • Used in combination with other antibiotics to treat tuberculosis; has activity only against Mycobacterium tuberculosis

  • Disadvantages: many side effects; liver toxicity; dosage must be reduced in patients with renal dysfunction, myalgia, nausea, and vomiting

PRACTICE POINT

Some of the antituberculosis antibiotics are supplied as packages that include the multiple drugs included in a given regimen. These include Rifater (pyrazinamide, isoniazid, and rifampin) and Rifamate (isoniazid and rifampin).

Other antimycobacterial drugs include aminosalicylic acid, capreomycin, ethionamide, rifabutin, and rifapentine. These are used infrequently in cases of resistant disease or patients who do not respond to other therapies. Their pronunciations, brand names, routes of administration, and dosage forms are included in Medication Table 27-3 along with those of the antituberculosis drugs described above. Table 27-4 summarizes types of infection, likely organisms, and first- and second-line antibiotic choices.

TABLE 27-4.

Empiric Treatment of Common Infections

Site of Infection

Likely Organism

First-Line Agent

Second-Line Agent

Skin infection

Staphylococcus sp., Streptococcus sp.

Antistaphylococcal penicillins (PCNs), 1st-generation cephalosporin

Vancomycin (if methicillin-resistant Staphylococcus aureus [MRSA] is suspected or severe allergy to PCN)

Urinary tract

Escherichia coli, Proteus, Klebsiella, Enterococcus

Nitrofurantoin, fosfomycin, sulfamethoxazole/trimethoprim

Fluoroquinolone (levofloxacin and ciprofloxacin)

Beta-lactam (amoxicillin/clavulanate, ampicillin/sulbactam, cefdinir cefaclor, cefpodoxime, cephalexin)

Respiratory

Atypical, Streptococcus pneumoniae, Haemophilus influenzae (community acquired), MRSA, Pseudomonas (hospital-acquired)

Community: azithromycin, fluoroquinolone (levofloxacin, moxifloxacin), amoxicillin, doxycycline, amoxicillin/clavulanate, 3rd-generation cephalosporin (ceftriaxone, cefpodoxime, cefotaxime), ceftaroline

Hospital: Vancomycin, linezolid, piperacillin/tazobactam, cefepime, ceftazidime, meropenem, imipenem, fluoroquinolone (levofloxacin, ciprofloxacin), aminoglycosides

Intra-abdominal

Anaerobes, E. coli

Community: 2nd-generation cephalosporin, ertapenem, moxifloxacin, tigecycline, piperacillin-tazobactam; combination options are cefazolin, cefuroxime, ceftriaxone, cefepime, levofloxacin with metronidazole

Hospital: Meropenem, piperacillin-tazobactam. Combination options are levofloxacin or cefepime with metronidazole

Antibiotic Selection

Several factors must be considered for antibiotic selection. First, the clinician must determine the goal of therapy. In some cases, this will be to prevent an infection following surgery or another procedure. This is known as surgical prophylaxis. Not all surgeries or procedures require the patient to receive antibiotic therapy. Treatment with antibiotics is recommended for patients with valvular heart disorders or artificial joints, as well as those who are immunosuppressed, or otherwise at high risk for infection. Procedures carrying a higher risk of bacterial infections are those performed in the mouth, GI tract, and genitourinary tract. If prophylactic antibiotic therapy is indicated, antibiotic selection is based on the normal flora that resides in the location of the procedure. For example, a patient at risk for endocarditis (infection of the heart valves or lining of the heart) who is scheduled for a dental procedure would receive amoxicillin 2,000 mg orally 30–60 minutes prior to the procedure. Amoxicillin has activity against those organisms that inhabit the oral cavity. The goal of using amoxicillin in this patient is to prevent the bacteria that enter the bloodstream (from the dental procedure) from causing an infection in the heart. As stated earlier, not all patients need antibiotic prophylaxis; it is routinely used for those with risk factors for infectious processes. There are several guidelines available for prophylactic antibiotic dosing for various procedures.

In other cases, the goal of therapy will be to treat an infection that has already developed. Regardless of the goal, antibiotic selection is determined by the most likely organism to cause an infection based on the location of the infectious process or type of surgery performed. Empiric therapy refers to the selection of an antibiotic based on the organisms most commonly encountered at the site of the infection prior to obtaining culture results. Finally, definitive treatment refers to antibiotic selection that has activity toward a known pathogen based on the results of culture and sensitivity testing. In addition, the following factors must be considered for antibiotic selection.

  • Allergies or history of adverse drug reactions to certain antibiotics (cross-sensitivity of antibiotic class)

  • Patient’s age (FDA approval for specified ages or known toxicity within certain age groups)

  • Genetic or metabolic abnormalities (drug accumulation/toxicity)

  • Renal (kidney) function (dose adjustment if renally excreted)

  • Hepatic (liver) function (dose adjustment if hepatically metabolized)

  • Site of infection (drug distribution/tissue penetration)

  • Pregnancy/lactation (safe use in pregnancy or lactation)

  • Concomitant drug therapy (drug interactions)

  • Concomitant disease states (drug/disease interaction)

  • Antibiogram (hospital-specific susceptibility and resistance patterns)

  • Resistance patterns

Combination Therapy

Combination therapy refers to the use of more than one antibiotic to treat an infection. The concept behind combination therapy is to achieve one of the following: broaden antimicrobial coverage for a suspected organism or multiple organisms, improve efficacy though synergistic activity, and help overcome bacterial resistance. Many infections, such as pneumonia and hospital-acquired (nosocomial) infections, are treated with combination therapy for the reasons listed earlier. In addition, when patients are started on empiric therapy and the organism is yet to be identified, they may be placed on multiple antibiotics until the cultures and sensitivities are reported. At that time, the clinician may narrow down the antibiotic regimen based on the results and patient response.

CASE?

Why do you think G. F. was started on both ceftriaxone and azithromycin?

Patient Monitoring

Patient monitoring begins once antibiotic therapy is initiated. This includes monitoring the patient for safety, efficacy, response, and completion of therapy. Safety monitoring includes watching for both allergic reactions and adverse drug events associated with the selected antibiotic(s). As with all medications, the patient’s allergies must be reviewed prior to any medication being dispensed. Antibiotic allergies range from nausea to anaphylaxis. If a patient is allergic to penicillin, there is a small chance of cross allergy to other antibiotics in the beta-lactam class. For mild reactions to penicillins, such as nausea or a mild rash, most clinicians will confidently dispense an antibiotic in a different beta-lactam group, such as a cephalosporin. If the patient reports an incident of anaphylactic reaction to penicillin, an antibiotic from a different class altogether (ie, fluoroquinolone) should be used to ensure patient safety. Allergies are often a class effect and antibiotics from a different class should be used for severe allergies to avoid additional reactions.

In addition to allergies, patients should be monitored for adverse drug reactions. It is important for clinicians to be familiar with the common side effects of different antibiotic classes to be able to properly monitor the patient. Adverse reactions to antibiotics include the side effects one may experience while taking the medication. They can also be the result of a drug interaction that increases the chance of a known adverse reaction or unwanted effect due to altered drug absorption, distribution, and elimination.

It is important for clinicians to monitor patients for response to antibiotic therapy, ensuring efficacy of the antibiotic(s) selected to treat the infection. As mentioned earlier, cultures are obtained to help identify the pathogenic organism(s). These cultures are monitored for growth, identification, and sensitivity of the organism to specific antibiotics. Commonly, cultures may remain negative and no organism(s) grow in the culture obtained. If this is the case, the patient’s laboratory and physical condition will be monitored to determine the efficacy of the selected therapy. In cases where cultures do grow, the clinician will review the identified organism(s) and compare it to the antibiotic regimen the patient is receiving to ensure proper antimicrobial coverage. If sensitivities are reported, the clinician may modify the regimen to an antibiotic that is more effective against the specific pathogen. Whenever possible, therapy is adjusted to provide coverage for only those organisms isolated or suspected. This is an important factor in reducing the possible development of resistant organisms.

Patient-specific values, such as the WBC count and temperature, are monitored closely to determine if the patient is responding to antibiotic therapy. A baseline WBC count is obtained and monitored closely thereafter. If the WBC count trends downward, it is a good indication the patient is responding to antibiotic therapy and improving. If the patient’s WBC count increases or continues to increase despite antibiotic therapy, it may be a sign of treatment failure. A patient’s temperature is also monitored for response to therapy. Like the WBC count, if the temperature was elevated at baseline and the patient becomes afebrile and maintains an afebrile state, it is a good indication that the patient is responding to therapy. Alternatively, if the temperature remains elevated or spikes, it may be a sign of treatment failure.

Finally, other diagnostic tests may be reordered to evaluate for continued or worsening infection. A repeat chest x-ray can be obtained for patients who are worsening on therapy to determine if the initial infection has not responded or if there may be a new infection that may warrant a change in therapy. Clinicians must also determine duration of therapy for antibiotic use based on the type and severity of infection being treated. There are several guidelines available for various infections that serve as treatment suggestions for both selection of antibiotic therapy and duration of treatment. Although these guidelines provide recommendations for duration of therapy, it is important to also evaluate the clinical response of the patient and adjust the duration based on response. In some cases, a longer duration of therapy may be warranted.

Duration of treatment is not only important to prevent treatment failure but also to help prevent antibiotic resistance. Often patients start to feel better and do not finish their course of antibiotics. This may lead to bacterial resistance as the pathogenic organism(s) may not be completely eradicated.

PRACTICE POINT

Antibiotic treatment often continues after the symptoms of an infection have disappeared. It is important that patients complete the full prescribed course of an antibiotic treatment, even if they feel cured, to prevent recurrence of the infection and the development of resistant strains.

CASE?

After 48 hours of IV antibiotics, G. F.’s breathing has improved and his WBC count has become lower. Does this mean it is time to discontinue therapy and send him home?

Prevention of infection is the best and most effective medicine. Handwashing is the most important and effective way to limit the spread of infectious organism(s). In hospital settings, many measures are in place to limit the number of hospital-acquired infections. These include the proper use of hand sanitizer, surveillance of employee handwashing, limiting contact with patients with highly contagious organisms (known as isolation), and monitoring of patients’ IV and urinary catheters, which can increase the risk of patients getting a hospital-acquired infection.

SUMMARY

Bacteria live among us and reside in our bodies as normal flora that helps us fight off other invading organisms and assist with many important functions in various organ systems. Our bodies have various natural defenses that assist normal flora in providing protection against invading organisms. When these natural defenses fail or breakdown, normal flora can become pathogenic and cause infection. Once an infection occurs, the body’s immune system starts the process of attacking the pathogen and inhibiting the replication of the pathogen. Every system in the body is susceptible to infection. In most cases, patients are febrile and have elevated WBCs that are consistent with infection. The location of the infection determines the type of disease or illness that occurs. The patient usually exhibits signs and symptoms that are specific to the type of infection. The signs and symptoms of the infection can guide the clinician regarding the most likely organism causing the infection. Depending on the type of infection and patient history, empiric antibiotic therapy is initiated. If bacterial resistance is suspected, broader coverage may be initiated. Risk factors for bacterial resistance include recent prior antibiotic use, and history of prior resistant organisms. Samples from the patient are usually cultured in hopes of identifying the offending organism and also to determine the susceptibility of that organism to various antibiotics. When the cultures reveal the infecting organism(s), the initial empiric therapy can be changed, if necessary, to agents chosen to treat the specific infection.

There are several antibiotic classes that cover specific organisms and each has specific indications for use. Once antibiotic therapy is initiated, patients are monitored for safety and for efficacy. Safety includes monitoring for allergic reactions and adverse reactions or side effects. Efficacy refers to signs of improvement and eradication of the organism(s). Monitoring cultures and sensitivities allows the clinician to modify empiric therapy to target the specific organism(s) identified and use the most effective agent based on sensitivities. A patient’s vital signs and laboratory values allow the clinician to determine if a patient is improving.

Over the years, bacteria have “learned” many methods to become resistant to antibiotics. Every year new antibiotics are developed to combat resistant organisms but not at the rate of bacterial resistance that is occurring. One way to slow the development of resistance is with the proper use of antibiotic regimens, with clinicians choosing an agent with the narrowest spectrum that includes the infecting organism and treating the infection for the optimal length of time.

ACKNOWLEDGMENT

The author wishes to acknowledge the work of John Flanigan, PharmD, BCNSP, James Adams, PharmD, BCPS, and Catherine W. Davis, PharmD, BCPS on this chapter in the first edition of this text.

REFERENCES

  • 1.

    Whitman WB, Coleman DC, Wiebe WJ. Proc Natl Acad Sci USA. 1998;95:65786583.

  • 2.

    DiPiro JT, Talbert RL, Yee GC, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. New York, NY: McGraw-Hill; 2020.

  • 3.

    Brunton LL, Hillal-Dandan R, Knollmann BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. New York, NY: McGraw-Hill; 2017.

  • 4.

    Macy E, Blumenthal KG. Are cephalosporins safe for use in penicillin allergy without prior allergy evaluation? J Allergy Clin Immunol Pract. 2018;6:8289.

CHAPTER RESOURCE

AHFS Drug Information 2019. Bethesda, MD: American Society of Health-System Pharmacists; 2019.

REVIEW QUESTIONS

  1. What are some ways that bacteria become resistant to antibiotics?

  2. What factors should be considered when selecting an antibiotic to treat an infection?

  3. Describe the difference between using antibiotics for surgical prophylaxis and empiric treatment of an infection.

  4. Why is it important for patients to finish their full prescribed course of antibiotics even if it extends for several days after they feel completely better?

  5. Why are beta-lactamase inhibitors added to penicillins but not to fluoroquinolones?

MEDICATION TABLES

MEDICATION TABLE 27-1.

The Penicillinsa

Agent (pronunciation)

Brand Name

Dosage Form

Route

Natural

Penicillin G benzathine (pen i SILL in) (BENZ a theen)

Bicillin L-A

Suspension

Intramuscular (IM)

Penicillin G potassium (pen i SILL in) (poe TAS ee um)

Pfizerpen-G

Solution

Injection

Penicillin G procaine (pen i SILL in) (PROE kane)

Suspension

IM

Penicillin V potassium (pen i SILL in) (poe TAS ee um)

Tablet, solution

Oral

Aminopenicillins

Amoxicillin (a mox i SIL in)

Tablet, capsule, suspension

Oral

Moxatag

Extended-release tablet

Oral

Amoxicillin/clavulanate (a mox i SIL in) (KLAV yoo la nate)

Augmentin

Tablet, suspension

Oral

Ampicillin (am pi SILL in)

Capsule, suspension

Oral

Solution

Injection

Ampicillin/sulbactam (am pi SILL in) (sul BAK tam)

Unasyn

Solution

Injection

Penicillinase-Resistant (antistaphylococcal)

Dicloxacillin (dye klox a SILL in)

Capsule

Oral

Nafcillin (naf SILL in)

Nallpen

Solution

Injection

Oxacillin (ox a SILL in)

Bactocill

Solution

Injection

Extended Spectrum

Piperacillin/tazobactam (pi PER a sil in) (ta zoe BAK tam)

Zosyn

Solution

Injection

a

Pronunciations have been adapted with permission from USP Dictionary of USAN and International Drug Names (USP Dictionary) © 2022.

MEDICATION TABLE 27-2.

Cephalosporins and Beta-Lactam Antibioticsa

Agent (pronunciation)

Brand Name

Dosage Form

Route

First Generation

Cefazolin (sef A zoe lin)

Kefzol

Premixed solution, powder for reconstitution

Intravenous (IV), intramuscular (IM)

Cefadroxil (sef a DROX il)

Duricef

Capsule, tablet (as hemihydrate and monohydrate); suspension

Oral

Cephalexin (sef a LEX in)

Keflex

Capsule, suspension, tablet

Oral

Second Generation

Cefaclor (SEF a klor)

Capsule, powder for suspension, extended-release tablet

Oral

Cefuroxime (se fyoor OX eem)

Zinacef

Premixed solution; powder for reconstitution

IV

Ceftin

Suspension, tablet

Oral

Cefprozil (sef PROE zil)

Suspension, tablet

Oral

Cefotetan (SEF oh tee tan)

Cefotan

Powder for reconstitution

IV, IM

Cefoxitin (se FOX i tin)

Mefoxin

Premixed solution, powder for reconstitution

IV, IM

Third Generation

Cefdinir (SEF di ner)

Omnicef

Capsule, suspension

Oral

Cefditoren (sef DIT or in)

Spectracef

Tablet

Oral

Cefixime (sef IX eem)

Suprax

Suspension, capsule, tablet

Oral

Cefotaxime (sef oh TAKS eem)

Claforan

Premixed solution, powder for reconstitution

IV, IM

Cefpodoxime proxetil (sef pode OX eem)

Suspension, tablet

Oral

Ceftazidime (SEF tay zi deem)

Fortaz, Tazicef

Premixed solution, powder for reconstitution

IV, IM

Ceftibuten (sef TYE byoo ten)

Cedax

Capsule, suspension

Oral

Ceftriaxone

(sef trye AX one)

Rocephin

Premixed solution, powder for reconstitution

IV, IM

Fourth Generation

Cefepime (SEF e peem)

Maxipime

Premixed solution, powder for reconstitution

IV, IM

Fifth Generation

Ceftaroline fosamil (sef TAR oh line) (FOS a mil)

Teflaro

Powder for reconstitution

IV

Cepahlosporin/Beta-Lactamase Combination

Ceftazidime/Avibactam (SEF tay zi deem) (a vi BAK tam)

Avycaz

Powder for reconstitution

IV

Ceftolozane/Tazobactam (sef TOL oh zane) (taz oh BAK tam)

Zerbaxa

Powder for reconstitution

IV

Siderophere Cephalosporin

Cefiderocol (SEF I DER oh kol)

Fetroja

Powder for reconstitution

IV

Carbapenems

Doripenem (dor i PEN em)

Doribax

Powder for reconstitution

IV

Ertapenem (er ta PEN em)

Invanz

Powder for reconstitution

IV, IM

Imipenem/cilastatin (i mi PEN em) (sye la STAT in)

Primaxin

Powder for reconstitution

IV

Meropenem (mer oh PEN em)

Merrem

Powder for reconstitution

IV

Carbapenem/Beta-Lactamase Combination

Meropenem/Vaborbactam (mer oh PEN em) (va bor BAK tam)

Vabomere

Powder for reconstitution

IV

Imipenem/cilastin/relebactam (i mi PEN em) (sye la STAT in) (REL e BAK tam)

Recarbrio

Powder for reconstitution

IV

Monobactam

Aztreonam (AS tree oh nam)

Azactam

Premixed solution, powder for reconstitution

IV, IM

Cayston

Powder for reconstitution (nebulizer solution)

Inhalation

a

Pronunciations have been adapted with permission from USP Dictionary of USAN and International Drug Names (USP Dictionary) © 2022.

MEDICATION TABLE 27-3.

Additional Anti-infective Classesa

Agent (pronunciation)

Brand Name

Dosage Form

Route

Fluoroquinolones

Ciprofloxacin (sip roe FLOX a sin)

Ceftraxal

Solution

Otic

Otiprio

Suspension

Otic

Ciloxan

Solution, ointment

Ophthalmic

Cipro

Solution

IV

Cipro

Tablet

Oral

ProQuin XR

Extended-release tablet

Oral

Levofloxacin (lee voe FLOX a sin)

Levaquin

Premixed solution, injection solution, oral solution, oral tablet

IV, oral

Iquix, Quixin

Solution

Ophthalmic

Moxifloxacin (mox i FLOX a sin)

Avelox IV

Premixed solution

IV

Avelox IV

Tablet

Oral

Avelox ABC Pack

Tablet

Oral

Ofloxacin (oh FLOX a sin)

Tablet, solution

Oral, otic

Ocuflox

Solution

Ophthalmic

Delafloxacin (del a FLOX a sin)

Baxdela

Powder for reconstitution

IV

Baxdela

Tablet

Oral

Aminoglycosides

Amikacin (am i KAY sin)

Solution

IM, IV

Gentamicin ( jen ta MYE sin)

Solution (concentrated and premixed in NS)

IM, IV, ophthalmic

Neomycin (nee oh MYE sin)

Neo-Fradin

Solution, tablet

Oral

Streptomycin (strep toe MYE sin)

Powder for reconstitution

IM, IV

Tobramycin (toe bra MYE sin)

Premixed solution, powder for reconstitution, injection solution

IM, IV, ophthalmic

Tobi

Solution for nebulization

Inhalation

Plazomicin (pla zoe MYE sin)

Zemdri

Solution

IV

Macrolides

Azithromycin (as ith roe MYE sin)

Zithromax

Powder for reconstitution, powder for oral suspension, tablet

IV, oral

Zmax

Extended-release microspheres for suspension

Oral

Zithromax TRI-PAK, Zithromax Z-PAK

Tablet (dose pack)

Oral

Clarithromycin (kla RITH roe mye sin)

Biaxin, Biaxin XL

Tablet, extended-release tablet, suspension

Oral

Erythromycin (er ith roe MYE sin)

E.E.S., EryPed, Ery-Tab, PCE

Delayed-release capsule, granules for suspension, powder for suspension, tablet, delayed-release tablet

Oral

Erythrocin Lactobionate-IV

Powder for reconstitution

IV

Ilotycin

Ointment

Ophthalmic

Erythro-RX (USP 100%)

Powder for prescription compounding

RX formulations

Akne-mycin, Ery

Gel, pads, solution

Topical

Fidaxomicin (fye DAX oh mye sin)

Dificid

Tablet

Oral

Tetracyclines

Doxycycline (doks i SYE kleen)

Oracea

Capsule, delayed release

Oral

Ocudox, Oraxyl, Vibramycin

Capsule (hyclate), powder for suspension, syrup

Oral

Adoxa, Monodox

Capsule, tablet (monohydrate)

Oral

Doxy 100

Powder for reconstitution

IV

Alodox, Periostat

Tablet

Oral

Doryx

Delayed-release tablet

Oral

Atridox

Extended-release liquid

Subgingival

Minocycline (mi noe SYE kleen)

Minocin

Capsule, powder for reconstitution

Oral, IV

Dynacin

Tablet

Oral

Solodyn

Extended-release tablet

Oral

Arestin

Sustained-release microspheres (powder)

Subgingival

Tetracycline (tet ra SYE kleen)

Capsule

Oral

Tigecycline (tye ge SYE kleen)

Tygacil

Powder for reconstitution

IV

Omadacycline (oh MAD a SYE kleen)

Nuzyra

Tablet, powder for reconstitution

Oral, IV

Eravacycline (ER a va SYE kleen)

Xerava

Powder for reconstitution

IV

Glycopeptides

Telavancin (tel a VAN sin)

Vibativ

Powder for reconstitution

IV

Vancomycin (van koe MYE sin)

Vancocin

Capsule, premixed solution, powder for reconstitution

Oral, IV

Dalbavancin (dal ba VAN sin)

Dalvance

Powder for reconstitution

IV

Oritavancin (or it a VAN sin)

Orbactiv

Powder for reconstitution

IV

Sulfonamides

Co-trimoxazole (sulfamethoxazole with trimethoprim) (coe try MOX a zole)

Injection solution, oral suspension

IV, oral

Bactrim, Septra

Tablet

Oral

Bactrim DS, Septra DS

Tablet, double strength

Oral

Sulfacetamide (sul fa SEE ta mide)

Bleph-10, Sulfamide

Solution

Ophthalmic

Carmol Scalp Treatment, Klaron, Ovace, Rosula, Seb-Prev

Foam, cream, gel, lotion, pad, soap, suspension, shampoo, emulsion, ointment

Topical

Sulfadiazine (sul fa DYE a zeen)

Tablet, cream

Oral, Topical

Erythromycin and Sulfisoxazole (er ith roe MYE sin) (sul fi SOX a zole)

E.S.P.

Powder for suspension

Oral

Antimycobacterials

Clofazamine (kloe FAZ i meen)

Lamprene

Capsule

Oral

Dapsone (DAP sone)

Tablet

Oral

Antituberculosis

Aminosalicylic acid (a mee noe sal i SIL ik) (AS id)

Paser

Delayed-release granules

Oral

Capreomycin

(kap ree oh MYE sin)

Capastat

Powder for reconstitution

IV, IM

Cycloserine (sye kloe SER een)

Seromycin

Capsule

Oral

Ethambutol (e THAM byoo tole)

Myambutol

Tablet

Oral

Ethionamide (e thye on A mide)

Trecator

Tablet

Oral

Isoniazid (eye soe NYE a zid)

Injection solution, oral solution, tablet, syrup

IM, oral

Pyrazinamide (peer a ZIN a mide)

Tablets

Oral

Rifabutin (RIF a byoo tin)

Mycobutin

Capsule

Oral

Rifampin (RIF am pin)

Rifadin

Capsule, powder for reconstitution

Oral, IV

Rifapentine (RIF a pen teen)

Priftin

Tablet

Oral

Miscellaneous

Chloramphenicol (klor am FEN i kol)

Powder for reconstitution

IV

Clindamycin (klin da MYE sin)

Cleocin HCl

Capsule

Oral

Cleocin Pediatric

Granules for solution

Oral

Cleocin Phosphate

Premixed solution, injection solution, vagin*l cream

IV, Topical

Daptomycin (dap toe MYE sin)

Cubicin

Powder for reconstitution

IV

Linezolid (li NE zoh lid)

Zyvox

Premixed solution, powder for oral suspension, tablet

Oral, IV

Tedizolid (ted eye ZOE lid)

Sivextro

Powder for reconstitution, tablet

Oral, IV

Metronidazole (me troe NI da zole)

Flagyl

Capsule, premixed solution, tablet, cream, gel, lotion

Oral, IV, Topical

Flagyl ER

Extended-release tablet

Oral

Rifaximin (ri FAX i men)

Xifaxan

Tablet

Oral

Quinupristin-dalfopristin (kwi NYOO pris tin) (dal FOE pris tin)

Synercid

Powder for reconstitution

IV

Colistimethate (koe lis ti METH ate)

Coly-Mycin M

Powder for reconstitution

IM, IV

Nitrofurantoin (nye troe fyoor AN toyn)

Furadantin

Capsule

Oral

Macrobid

Capsule

Oral

Macrodantin

Suspension

Oral

Fosfomycin (fos foe MYE sin)

Monurol

Packet, powder for reconstitution

Oral, IV

Lefamulin (le FAM ue lin)

Xenleta

Solution, tablet

Oral, IV

IM = intramuscular; IV = intravenous; NS = normal saline.

a

Pronunciations have been adapted with permission from USP Dictionary of USAN and International Drug Names (USP Dictionary) © 2022.

Chapter 27  Bacterial Infections (2024)
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