Antimicrobial agents
After reading this chapter, the reader will be able to:
1. Define terms that pertain to antimicrobial agents
3. Describe the process involved in bacterial susceptibility testing
4. Discuss possible outcomes of antimicrobial combinations
5. List the various classes of the penicillins
6. List the various classes of the cephalosporins
7. Recognize similarities between members of the macrolides
8. Recognize similarities between members of the quinolones
9. List four mechanisms of action of antibacterials
10. List five commonly used antimycobacterials
11. Describe the commonly used azole antifungals and how they differ in spectrum of activity
12. Discuss similarities between members of the echinocandins
The antimicrobial properties of fermented beverages, moldy soybean curd, and spices were first described by the Chinese more than 2500 years ago.1 However, dissemination and acceptance of such knowledge did not take root until the early 1900s. The discovery of microscopic “little animals” by van Leeuwenhoek paved the way for Koch to validate that these “little animals,” or germs, caused disease. Before Koch’s work, almost no one believed that germs caused human disease. Despite the discovery of this important relationship, it would take numerous paradigm shifts and incredible luck before the discovery and usage of antimicrobials transpired.2
The sulfanilamides, azo compounds used in the German dye industry, were the first class of agents discovered to have antibacterial activity. These compounds were initially unsuccessful and required multiple modifications to reduce their unpleasant side effects. In 1928, Fleming discovered the first antibiotic, which he named penicillin. Fleming, similar to other scientists of the time, did not realize the utility of penicillin for systemic infections, however. A 1940 publication entitled “Penicillin as a Chemotherapeutic Agent” by Chain and colleagues3 set into motion what we now refer to as the “golden age” of antimicrobial chemotherapy.
The realization that living organisms may produce compounds that kill microbes is a relatively new concept. Since this realization, more than 30 classes of compounds have been identified from natural sources or created synthetically to treat infections resulting from bacteria, fungi, protozoa, and viruses. Techniques to identify organisms and to determine their susceptibility have also evolved over the years and are vital to the choice of the proper antimicrobial agent. In addition, other factors, such as the host, antimicrobial pharmacodynamics, antimicrobial combinations, and methods of monitoring therapy, are important parameters that need consideration before selecting an antimicrobial agent. This chapter focuses on these basic principles of antimicrobial therapy, provides a synopsis of mechanism of action and adverse effects, and emphasizes the clinical use of the various antimicrobial classes for the treatment of respiratory illnesses.1
Principles of antimicrobial therapy
Several factors require careful consideration before choosing a particular antimicrobial agent. Identification of the organism or organisms responsible for the infection is the first step toward treatment. Once the organism is isolated, antimicrobial susceptibility is determined according to standardized methods that can be replicated between laboratories. The susceptibility pattern of the organism narrows the choice of potential agents. Consideration must be given to host factors such as age, pregnancy, organ function, and site of infection. In addition, drug factors, such as available dosage forms, ease of administration, pharmacokinetics, potential adverse events, and cost, influence the choice of a specific agent.4
Identification of pathogen
In many clinical cases, the exact identity of the infecting organism is unknown. As a result, patients are treated empirically with an antimicrobial agent active against the organism or organisms that are most likely causing the infection. For example, 30% to 40% of patients with community-acquired pneumonia (CAP) fail to expectorate sputum, which prevents identification of a specific pathogen. However, research has shown, that the most common pathogens responsible for CAP include Streptococcus pneumoniae; Haemophilus influenzae; and atypical (intracellular) organisms such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. As a result, empiric therapy for CAP involves antimicrobials active against this spectrum of organisms. Conversely, identification of an organism from culture material does not always indicate an infection. For example, hospitalized patients often have growth of gram-negative bacilli (rods) in sputum samples. However, these organisms may represent colonization only, and not hospital-acquired (nosocomial) pneumonia. Common pathogens and treatment of specific respiratory infections are listed in Table 14-1.5
TABLE 14-1
Common Pathogens and Treatment of Respiratory Infections in Adults*
| RESPIRATORY INFECTION | COMMON PATHOGENS | POTENTIAL ANTIBIOTIC REGIMENS |
| Sinusitis | ||
| Acute (community acquired) | Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis | Amoxicillin-clavulanate or cefuroxime axetil or respiratory quinolone (levofloxacin or moxifloxacin or gemifloxacin) or macrolide/ketolide or TMP-SMX |
| Acute (hospital acquired) | Pseudomonas aeruginosa, Acinetobacter spp., Staphylococcus aureus | Ceftazidime or cefepime or aztreonam or a carbapenem and vancomycin |
| Chronic | Bacteroides spp., Peptostreptococcus spp., Fusobacterium spp. | Antibiotics are usually unsuccessful; sinus drainage may be required |
| Bronchitis | ||
| Acute | Mycoplasma pneumoniae, Chlamydia pneumoniae, Bordetella pertussis | Antibiotics are usually not indicated; however, doxycycline or macrolide may be considered |
| Exacerbation of chronic bronchitis | S. pneumoniae, H. influenzae, M. catarrhalis | Value of antibiotics is controversial; doxycycline or macrolide may be considered |
| Pneumonia | ||
| Community acquired | S. pneumoniae, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, Legionella pneumophila | Azithromycin, clarithromycin, telithromycin, or respiratory quinolone, or doxycycline or β-lactam (ceftriaxone, cefuroxime, amoxicillin-clavulanate) and a macrolide |
| Hospital acquired (nonneutropenic patient) | S. pneumoniae, P. aeruginosa | Cefepime, ceftazidime, or aztreonam or a carbapenem or piperacillin-tazobactam ± an aminoglycoside or ciprofloxacin ± vancomycin |
| Hospital acquired (neutropenic patient) | As listed for nonneutropenic patients and fungi such as Aspergillus spp., Pneumocystis carinii (especially if HIV positive) | Cefepime, a carbapenem, ceftazidime, or piperacillin-tazobactam + an aminoglycoside or ciprofloxacin ± vancomycin ± amphotericin B ± TMP-SMX |
| Aspiration suspected | S. pneumoniae, Bacteroides fragilis, Peptostreptococcus spp., Fusobacterium spp. | Amoxicillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam, clindamycin ± quinolone |
| Patient with cystic fibrosis | S. aureus, P. aeruginosa, Burkholderia cepacia | Aminoglycoside + piperacillin-tazobactam or ceftazidime, cefepime ± TMP-SMX (B. cepacia) |
| Empyema | ||
| Streptococcus milleri, B. fragilis, Enterobacteriaceae, Mycobacterium tuberculosis | Piperacillin-tazobactam or third-generation cephalosporin + clindamycin† |
HIV, Human immunodeficiency virus; TMP-SMX, trimethoprim-sulfamethoxazole.
*The potential treatments listed here are not listed in order of superiority. Choice of antimicrobials depends on the individual susceptibility pattern of the suspected organisms within the specific institution.
†See Table 14-7 for antimycobacterial regimens.
Susceptibility testing and resistance
Once an organism is isolated, susceptibility test results can usually be obtained within 24 hours. Several methods are commonly used to determine the susceptibility of isolated pathogens. The Kirby-Bauer disk diffusion test involves the use of antibiotic-impregnated disks that are placed on an agar plate heavily inoculated (105 colony-forming units [cfu]/mL) with the isolated bacteria. If the organism is susceptible to the antibiotic, a clear zone of inhibition (no growth of the organism) develops around the disk. The degree of susceptibility or resistance of the organism depends on the diameter of this circular zone of inhibition; that is, a larger diameter indicates greater sensitivity. Another disk diffusion test is the elliptical test, or E-test. The E-test strip is placed on an agar plate heavily inoculated with the isolated organism. The strip creates an antimicrobial gradient, which results in a clear elliptical zone of inhibition. This method allows the determination of the minimal inhibitory concentration (MIC). MIC is defined as the least concentration of antimicrobial that prevents visible growth. The Kirby-Bauer and E-test methods are illustrated in Figure 14-1.
Other methods include inoculation of the organism into serial dilutions of an antimicrobial in agar or, more commonly, in broth culture media (Figure 14-2). Automated systems such as Vitek (bioMérieux, Durham, N.C.) and MicroScan (Dade Behring, West Sacramento, Calif.) take advantage of broth microdilution methods to provide efficient and rapid susceptibility results. When susceptibility testing is performed in broth media, a small sample can be removed from the test tubes or microwells with no growth and used to inoculate agar plates. The lowest concentration of antimicrobial agent that prevents growth of the organism on the agar plate after a 24-hour incubation is termed the minimal bactericidal concentration (MBC). Drugs that inhibit the growth of bacteria but do not kill them are termed bacteriostatic. A bactericidal drug is one that kills the bacteria. Examples of bacteriostatic and bactericidal drugs are listed in Box 14-1.
Susceptibility testing is a crucial part of antimicrobial therapy because the empiric regimen may fail when used to treat infections with resistant organisms. Microorganisms, similar to all living things, have genetic variability that affects their susceptibility to antimicrobials. Selective pressure from extensive clinical and agricultural use of antibiotics is thought to play a primary role in the emergence of resistant bacteria. Mechanisms of bacterial resistance include the production of enzymes that degrade or modify antibiotics, alteration of bacterial cell walls or membranes, upregulation of antimicrobial efflux pumps, and alteration of the site of antimicrobial action. Table 14-2 lists important emerging resistant bacteria.4
Host factors
The safety and efficacy of an antimicrobial agent vary, based on the population of patients being treated.5 For example, bone marrow transplant recipients with an active infection may not improve despite use of the ideal antimicrobial agent because of their impaired immune function. Similarly, other immunocompromised hosts, such as patients with acquired immunodeficiency syndrome (AIDS), recipients of cancer chemotherapy or steroids, and solid organ transplant recipients, are also at risk of failing to improve on antimicrobial therapy. Other factors such as the altered pharmacokinetics of an antimicrobial can affect response to therapy. For example, the absorption of certain antimicrobials such as itraconazole (an antifungal agent) is increased in the presence of gastric acid; others, such as penicillin G, are degraded in the presence of acid. The pH of the stomach varies with age; older patients tend to have achlorhydria, and young children tend to have a higher gastric pH. As a result, these two populations may have enhanced absorption of penicillin and decreased absorption of itraconazole relative to the rest of the population.
Antimicrobials concentrate in varying degrees within organ systems and can influence the outcome of therapy. Clindamycin achieves excellent bone concentrations and is very useful for treatment of osteomyelitis resulting from susceptible organisms. Similarly, drugs such as the aminoglycosides, most fluoroquinolones, and penicillins achieve very high concentrations in the urine and are useful for the treatment of urinary tract infections (UTIs). Conversely, certain drugs, although active against the organism in vitro, cannot achieve adequate concentrations at the site of infection. For example, aminoglycosides cannot penetrate the blood-brain barrier to treat meningitis adequately in adults. The blood-brain barrier represents tight junctions between the epithelial cells of the capillary wall that prevent drugs from entering the central nervous system.4
Pharmacodynamics
Pharmacodynamics refers to the science of understanding the optimal effect of a drug as a function of its concentration and the in vitro activity (MIC) against an organism. The pharmacodynamic properties of an antimicrobial are measured in vitro by using time-kill studies. These studies measure the rate and extent of microorganism killing when exposed to varying concentrations of antimicrobials. If the microbial kill rate increases proportionally with drug concentration, the antimicrobial is said to have a concentration-dependent effect. If the microbial kill rate is influenced by the time of drug concentration above the MIC, the antimicrobial is defined as time-dependent (or concentration-independent). Another pharmacodynamic phenomenon exhibited by antimicrobials is known as the postantibiotic effect (PAE). The PAE refers to the sustained suppression of bacterial growth even after the concentration of the antibiotic declines below detectable levels. The length of the PAE varies by the type of organism and the drug. Generally, time-dependent drugs, such as β-lactams, have short PAEs, whereas concentration-dependent drugs, such as aminoglycosides, metronidazole, and quinolones, have longer PAEs. Agents with a short PAE should be dosed frequently, and longer dosing intervals should be used for antimicrobials having a long PAE. These pharmacodynamic properties have been shown in vitro and in numerous animal studies. Clinical trials validating these principles are ongoing, and practical guidelines to incorporate pharmacodynamics in clinical practice are under study.4
Antimicrobial combinations
Empiric regimens must often cover a broad spectrum of organisms, which occasionally requires the use of two or more classes of antimicrobials. Ideally, the regimen should be narrowed after the specific organism has been isolated and susceptibilities are determined. Certain infections are polymicrobial, and in certain settings the use of antimicrobial combinations is justified. When antimicrobials are used in combination, it is important to know whether these agents act synergistically or are antagonistic. Synergy is shown in vitro when the combined effect of two antimicrobials is greater than their added effect (i.e., 1 + 1 > 2). Antagonism occurs when the effect of the combined drug is lower than the effect expected from either agent alone (i.e., 1 + 1 < 1). Antagonism may result in an unfavorable response, and such drug combinations should be avoided. A classic example of antagonism was the use of tetracycline and penicillin in children with pneumococcal meningitis. The mortality associated with the use of combination therapy was three times higher than the use of penicillin alone. Conversely, synergistic combinations have played a vital role in the treatment of resistant Pseudomonas infections in patients with cystic fibrosis. These patients have recurrent bouts of pseudomonal pneumonia and are often colonized with resistant species. Certain synergistic combinations of β-lactams and aminoglycosides have been shown to curb the development of resistance and to improve outcomes.4
Monitoring response to therapy
The use of antimicrobials can be associated with significant toxicities. The agent amphotericin B, which is used to treat fungal infections such as pulmonary aspergillosis, can cause significant renal dysfunction. Similarly, other agents can have adverse effects on the liver, gastrointestinal tract, neuromuscular system, hematologic system, heart, and lungs. The incidence of these adverse events varies among agents and is often reversible. Careful monitoring of patients receiving antimicrobials can prevent serious and potentially life-threatening adverse events.4
Antibiotics
Penicillins
The discovery of penicillin in 1928 by Fleming ultimately led to the creation of a broad class of antibiotics commonly referred to as β-lactams. β-lactam antibiotics include the penicillins, cephalosporins, monobactams, and carbapenems.6 The main constituent of these antibiotics is the β-lactam ring structure. Chemical manipulation of β-lactam side chains led to the development of new agents with enhanced spectra of antimicrobial activity compared with penicillin. Specific side-chain modifications of penicillin have resulted in a broad class that includes the natural penicillins, aminopenicillins, penicillinase-resistant penicillins, carboxypenicillins, and ureidopenicillins (Table 14-3). Penicillins have also been combined with β-lactamase inhibitors to overcome a common mechanism of bacterial resistance.
TABLE 14-3
Classification and Clinical Uses of Penicillins
| β-LACTAM CLASS (GENERIC NAME) | BRAND NAME | ROUTE | COMMON USES (MICROORGANISM) |
| Natural Penicillins | |||
| Penicillin G (potassium) | Pfizerpen | IM, IV | Streptococcus pyogenes, Neisseria meningitidis, Bacillus anthracis (anthrax), Clostridium perfringens (gangrene), Pasteurella multocida, Treponema pallidum (syphilis) |
| Penicillin G (procaine) | Wycillin | IM | |
| Penicillin G (benzathine) | Bicillin L-A | IM | |
| Penicillin V (potassium) | Pen-Vee K | PO | |
| Penicillinase-Resistant Penicillins | |||
| Oxacillin | Prostaphlin | PO, IM, IV | MSSA, MSSE |
| Nafcillin | Unipen | PO | |
| Dicloxacillin | Dynapen | PO | |
| Aminopenicillins | |||
| Ampicillin | Omnipen | PO, IM, IV | Listeria monocytogenes, Proteus mirabilis, Eikenella corrodens, Borrelia burgdorferi |
| Amoxicillin | Amoxil, Wymox | PO | |
| Carboxypenicillins | |||
| Carbenicillin | Geopen | PO, IM, IV | Pseudomonas aeruginosa, Enterobacteriaceae |
| Ticarcillin | Ticar | IV, IM | |
| Ureidopenicillins | |||
| Piperacillin | Pipracil | IM, IV | P. aeruginosa, Enterobacteriaceae |
| Penicillin plus β-lactamase Inhibitors | |||
| Amoxicillin–clavulanic acid Ampicillin-sulbactam |
Augmentin Unasyn |
PO IM, IV |
Increased activity against β-lactamase–producing strains S. aureus, Haemophilus influenzae, Moraxella catarrhalis, Proteus spp., Bacteroides spp. |
| Ticarcillin–clavulanic acid | Timentin | IV | P. aeruginosa, Enterobacteriaceae |
| Piperacillin-tazobactam | Zosyn | IV |
The penicillins generally are widely distributed throughout the body and are associated with relatively low levels of toxicity. Most penicillins are acid-labile (destroyed in the stomach) and therefore are poorly absorbed after oral administration. Most agents in this class are not metabolized but are excreted unchanged in the urine. Therefore, most penicillins require reductions in dosage for patients with renal dysfunction.7
Mode of action
Penicillins exert their pharmacologic activity by inhibiting cell wall synthesis. Penicillins bind to enzymes (penicillin-binding proteins) located within the cell wall and prevent cross-linking of the peptidoglycan structure necessary for cell wall development. In addition, penicillins activate an endogenous autolytic system within bacteria, which subsequently leads to cell lysis and death. Penicillins are bactericidal, exhibit time-dependent killing, and can act synergistically with aminoglycosides against some bacteria (i.e., Pseudomonas aeruginosa and enterococci).8
Clinical uses
Natural penicillins.
Benzylpenicillin (penicillin G) is the parent compound of this class. This agent may be administered by the parenteral (intravenous [IV]) or intramuscular (IM) route. Penicillin G procaine is used for intramuscular dosing only and provides a less painful alternative when sustained serum concentrations are required. Phenoxymethyl penicillin (penicillin V) resists degradation by gastric acid and can be administered orally (PO). Natural penicillins are effective primarily against gram-positive bacteria and anaerobes. Penicillin G is the drug of choice for the treatment of primary and secondary syphilis (Treponema pallidum) and pharyngitis caused by group A streptococci (Streptococcus pyogenes). Because of the increasing frequency of resistance in Staphylococcus aureus, S. pneumoniae, and Neisseria gonorrhoeae, penicillin G should no longer be considered the agent of choice for infections caused by these organisms.7
Penicillinase-resistant penicillins.
In an attempt to overcome the emergence of penicillinase-producing (β-lactamase–producing) staphylococci, semisynthetic penicillinase-resistant antibiotics were developed. These agents are commonly referred to as antistaphylococcal agents because of their excellent activity against S. aureus. Methicillin was the first agent in this class of antibiotics, followed by oxacillin, nafcillin, cloxacillin, and dicloxacillin. Chemical modification of penicillin by the addition of an acyl side chain prevents hydrolysis of the agents in the presence of penicillinase. This class has activity against gram-positive cocci (staphylococci and streptococci) and is routinely used in skin and soft tissue infections. These agents are ineffective in the treatment of infections caused by gram-negative organisms or anaerobes. Until the 1980s, these antibiotics were the mainstay of treatment against staphylococci. However, the emergence of methicillin-resistant staphylococci has greatly reduced the clinical effectiveness of these agents.7
Aminopenicillins.
Aminopenicillins were the first penicillin class developed that were considered clinically active against some gram-negative bacteria (Escherichia coli, H. influenzae). Ampicillin and amoxicillin are the primary antibiotics in this class. In contrast to penicillin, ampicillin and amoxicillin are stable in gastric acid and therefore are suitable for oral administration. Both ampicillin and amoxicillin are frequently used in infections with susceptible organisms of the respiratory (S. pneumoniae, H. influenzae) and urinary (E. coli) tracts.7
Carboxypenicillins.
With the emergence of more resistant gram-negative bacilli, penicillins with increased gram-negative activity were needed. Carbenicillin was the first penicillin to have activity against Pseudomonas aeruginosa. It was also active against most members of the family Enterobacteriaceae, including E. coli, Enterobacter, Proteus, Morganella, and Serratia. Subsequent modification of carbenicillin resulted in ticarcillin, which has even greater in vitro activity against P. aeruginosa and members of Enterobacteriaceae (including Klebsiella). Neither of these agents is considered to have appreciable activity against gram-positive organisms (staphylococci or streptococci). These agents are administered primarily in the intravenous form because high serum concentrations cannot be achieved with the oral formulations.7
Ureidopenicillins.
Although carbenicillin and ticarcillin provided increased gram-negative coverage, antimicrobial agents with enhanced antipseudomonal activity were still needed. The ureidopenicillins were developed to fill this need. Piperacillin is a penicillin antibiotic with enhanced gram-negative activity (especially against P. aeruginosa) and with fewer adverse reactions than carboxypenicillins. Ureidopenicillins also exhibit activity against streptococci and enterococci and many anaerobes. Piperacillin is the primary agent of this class and has been efficacious in the treatment of pneumonia, bacteremia, UTIs, osteomyelitis, and soft tissue infections.7
β-lactam and β-lactamase inhibitor combinations.
Certain bacteria have the ability to produce enzymes (β-lactamases) that destroy the activity of penicillins by disrupting the β-lactam structure. β-lactamase inhibitors were developed to overcome this form of resistance. Consequently, combination β-lactam and β-lactamase inhibitors have a large spectrum of activity, making them particularly useful in polymicrobial infections. At present, three β-lactamase inhibitors are approved for combination with penicillins: clavulanic acid, sulbactam, and tazobactam. β-lactamase inhibitors enhance the activity of β-lactams against β-lactamase–producing strains of S. aureus, Moraxella catarrhalis, E. coli, H. influenzae, Klebsiella species, and Bacteroides species.7
Adverse reactions and precautions
The most common adverse reaction to penicillins is hypersensitivity. Approximately 3% to 10% of the population are allergic to penicillin. Reactions vary in severity from a mild rash to life-threatening anaphylaxis. Patients allergic to a penicillin could be potentially allergic to all classes of β-lactams (cephalosporins, carbapenems). In addition to allergic reactions, hematologic reactions such as thrombocytopenia and increased bleeding times have been reported. Hematologic disturbances are thought to be greater with carboxypenicillins than with ureidopenicillins. Gastrointestinal disturbances (nausea, vomiting, and diarrhea) are more common with oral dosage forms of penicillins, especially ampicillin. Interstitial nephritis has occurred most commonly with methicillin (not commercially available) but may occur with other penicillins as well. Central nervous system toxicities (i.e., seizures) have been reported with penicillins. Patients with an underlying seizure disorder and patients with renal insufficiency are at greatest risk for developing this complication.7
Cephalosporins
The cephalosporins include a large group of antimicrobials that are structurally related to the penicillins. Discovered in the 1940s as a microbial by-product of the fungus Cephalosporium acremonium, this class is now widely used in clinical practice. Similar to the penicillins, this class exhibits bactericidal activity, is distributed throughout the body, and produces relatively few adverse effects. Cephalosporins are used for various clinical indications and are available in oral and intravenous formulations (Table 14-4). Agents from this class have been loosely grouped into “generations” based on their spectrum of activities. At present there are four generations (classes) of cephalosporins.
TABLE 14-4
Classification and Clinical Uses of Cephalosporins
| CEPHALOSPORIN (GENERIC NAME) | BRAND NAME | ROUTE | COMMON USES (MICROORGANISM) |
| First Generation | |||
| Cefadroxil | Duricef | PO | MSSA, streptococci |
| Cephalexin | Keflex, Biocef | PO | |
| Cefazolin | Ancef, Kefzol | IM, IV | |
| Second Generation | |||
| Cefaclor | Ceclor | PO | MSSA, MSSE, Streptococcus pneumoniae, Klebsiella spp., Escherichia coli, Proteus spp., Haemophilus influenzae |
| Cefprozil | Cefzil | PO | |
| Cefuroxime axetil | Ceftin | PO | |
| Cefuroxime | Zinacef, Kefurox | IM, IV | |
| Cefotetan | Cefotan | IM, IV | As above and Bacteroides fragilis |
| Cefoxitin | Mefoxin | IM, IV | |
| Third Generation | |||
| Cefixime Cefpodoxime proxetil |
Suprax Vantin |
PO PO |
Better activity than second-generation cephalosporins against Klebsiella, E. coli, Proteus spp., H. influenzae, Enterobacter spp. |
| Ceftibuten | Cedax | PO | |
| Cefdinir | Omnicef | PO | |
| Cefotaxime | Claforan | IM, IV | |
| Ceftriaxone | Rocephin | IM, IV | |
| Ceftizoxime | Cefizox | IM, IV | |
| Ceftazidime | Fortaz, Tazidime | IM, IV | As above and P. aeruginosa |
| Cefoperazone | Cefobid | IM, IV | |
| Fourth Generation | |||
| Cefepime | Maxipime | IM, IV | MSSA, S. pneumoniae, Klebsiella, E. coli, Proteus spp., H. influenzae, P. aeruginosa, Enterobacter spp. |
Clinical uses
As a class, cephalosporins are active against a wide variety of organisms. Because of their broad spectrum of activity and low level of toxicity, these agents are commonly used for a wide variety of infections. The spectrum of activity differs for each cephalosporin generation. All cephalosporins are ineffective against enterococci.9
Adverse reactions and precautions
Similar to penicillins, the cephalosporins as a group are well tolerated. Hypersensitivity reactions occur in 1% to 3% of patients, with cross-reactivity of cephalosporins in patients with penicillin allergy ranging from 5% to 15%. Generally, patients with a penicillin allergy (limited to a rash) may be challenged with a cephalosporin. Cephalosporin use is contraindicated, however, in patients with a history of anaphylaxis to β-lactams.10
