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Introduction

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Bacteria are microorganisms that have circular double-stranded DNA and (except for Mycoplasma sp) cell walls.Only a small number are human pathogens.Bacteria are classified by several criteria, including morphology (see Table 1: Bacteria and Antibacterial Drugs: Classification of Common Pathogenic BacteriaTables). They may be cylindric (bacilli), spherical (cocci), or spiral (spirochetes). A few coccal, many bacillary, and most spirochetal species are motile. Gram-positive bacteria retain crystal violet dye after iodine fixation and alcohol decolorization, whereas gram-negative bacteria do not. Gram-negative bacteria have an additional outer membrane containing lipopolysaccharide (endotoxin). Bacteria may be additionally enclosed in capsules, which may (eg, with Streptococcus pneumoniae and Haemophilus influenzae) impair their ingestion by phagocytes. Other factors may enhance bacterial pathogenicity (see Biology of Infectious Disease: Factors Facilitating Microbial Invasion).

Table 1

Classification of Common Pathogenic Bacteria

Aerobic vs Anaerobic

Type

Organism

Aerobic

Gram-positive cocci, catalase-positive

Staphylococcus aureus (coagulase-positive), S. epidermidis (coagulase-negative), other coagulase-negative staphylococci

Aerobic

Gram-positive cocci, catalase-negative

Enterococcus faecalis , E. faecium , Streptococcus agalactiae (Group B streptococcus), S. bovis , S. pneumoniae , S. pyogenes (Group A streptococcus), Viridans group streptococci, S. anginosus , S. mutans

Aerobic

Gram-negative cocci

Moraxella catarrhalis , Neisseria gonorrhoeae , N. meningitidis

Aerobic

Gram-positive bacilli

Bacillus anthracis , Corynebacterium diphtheriae , C. jeikeium , Erysipelothrix rhusiopathiae , Gardnerella vaginalis (gram-variable)

Aerobic

Acid-fast bacilli

Mycobacterium avium complex, Mycobacterium kansasii, M. leprae , M. tuberculosis , Nocardia sp

Aerobic

Gram-negative bacilli

Enterobacteriaceae (Citrobacter sp, Enterobacter aerogenes , Escherichia coli , Klebsiella sp, Morganella morganii , Proteus sp, Providencia rettgeri , Salmonella typhi , other Salmonella sp, Serratia marcescens , Shigella sp, Yersinia enterocolitica , Y. pestis)

Aerobic

Fermentative, non-Enterobacteriaceae

Aeromonas hydrophila , Chromobacterium violaceum , Plesiomonas shigelloides , Pasturella multocida , Vibrio cholerae , V. vulnificus

Aerobic

Non-fermentative, non-Enterobacteriaceae

Acinetobacter calcoaceticus , Flavobacterium meningosepticum, Pseudomonas aeruginosa , Pseudomonas alcaligenes, other Pseudomonas sp, Stenotrophomonas maltophilia

Aerobic

Fastidious gram- negative coccobacilli and bacilli

Actinobacillus actinomycetemcomitans , Bartonella bacilliformis , B. henselae , B. quintana , Brucella sp, Bordetella sp, Eikenella corrodens , Haemophilus influenzae, other Haemophilus sp, Legionella sp

Aerobic

Curved bacilli

Campylobacter jejuni , Helicobacter pylori

Aerobic

Chlamydiaceae

Chlamydia trachomatis , Chlamydophila pneumoniae , C. psittaci

Aerobic

Rickettsiae

Rickettsia prowazekii , R. rickettsii

Aerobic

Mycoplasma

Mycoplasma pneumoniae

Aerobic

Treponemataceae (spiral organisms)

Borrelia burgdorferi , Leptospira sp, Treponema pallidum

Anaerobic

Gram-negative bacilli

Bacteroides fragilis, other Bacteroides sp, Fusobacterium sp, Prevotella sp

Anaerobic

Gram-negative cocci

Veillonella sp

Anaerobic

Non–spore-forming gram-positive bacilli

Actinomyces sp, Bifidobacterium sp, Eubacterium sp, Propionibacterium sp

Anaerobic

Endospore-forming gram-positive bacilli

Clostridium botulinum , C. perfringens , C. tetani, other Clostridium sp

Anaerobic

Gram-positive cocci

Gemella morbillorum , Peptococcus niger , Peptostreptococcus sp

Aerobic bacteria grow in culture in the presence of air. Anaerobic bacteria do not; facultative bacteria can grow either aerobically or anaerobically. Some bacteria (eg, Salmonella typhi , Legionella sp, Mycobacteria sp, and Chlamydia and Chlamydophila spp) preferentially reside and replicate intracellularly. Most others do so extracellularly.

Antibacterial drugs are derived from bacteria or molds or from de novo synthesis. “Antibiotic,” which is often used synonymously with “antibacterial drug,” technically refers only to antimicrobials derived from bacteria or molds. Antibacterials have many mechanisms of action, including inhibiting cell wall synthesis, activating enzymes that destroy the cell wall, increasing cell membrane permeability, and interfering with protein synthesis and nucleic acid metabolism.

Antibacterials sometimes interact with other drugs, raising or lowering serum levels of other drugs by increasing or decreasing their metabolism or various other mechanisms. The most clinically important interactions involve drugs with a low therapeutic ratio (ie, toxic levels are close to therapeutic levels); common agents are listed in Table 2: Bacteria and Antibacterial Drugs: Common Antibiotic InteractionsTables.

Table 2

Common Antibiotic Interactions

Drug

Toxicity Enhanced By

No Change With

Warfarin Some Trade Names
COUMADIN
Click for Drug Monograph

Azole antifungals

Cefoperozone*

Cefotetan Some Trade Names
CEFOTAN
Click for Drug Monograph
*

Chloramphenicol Some Trade Names
CHLOROMYCETIN
Click for Drug Monograph

Clarithromycin Some Trade Names
BIAXIN
Click for Drug Monograph

Doxycycline Some Trade Names
PERIOSTAT
VIBRAMYCIN
Click for Drug Monograph

Erythromycin Some Trade Names
ERY-TAB
ERYTHROCIN
Click for Drug Monograph

Fluoroquinolones ( ciprofloxacin Some Trade Names
CILOXAN
CIPRO
Click for Drug Monograph
, levofloxacin Some Trade Names
IQUIX
LEVAQUIN
QUIXIN
Click for Drug Monograph
, ofloxacin Some Trade Names
FLOXIN
Click for Drug Monograph
)

Metronidazole Some Trade Names
FLAGYL
Click for Drug Monograph

Rifampin Some Trade Names
RIFADIN
RIMACTANE
Click for Drug Monograph
(decreased PT)

Sulfonamides

Aminoglycosides (IV)

Cephalosporins (some)

Penicillins

Tetracycline Some Trade Names
ACHROMYCIN V
TETRACYN
TETREX
Click for Drug Monograph

Trimethoprim Some Trade Names
PROLOPRIM
TRIMPEX
Click for Drug Monograph

Theophylline Some Trade Names
ELIXOPHYLLIN
THEO-DUR
Click for Drug Monograph

Clarithromycin Some Trade Names
BIAXIN
Click for Drug Monograph

Ciprofloxacin Some Trade Names
CILOXAN
CIPRO
Click for Drug Monograph

Erythromycin Some Trade Names
ERY-TAB
ERYTHROCIN
Click for Drug Monograph

Rifampin Some Trade Names
RIFADIN
RIMACTANE
Click for Drug Monograph
decreases theophylline Some Trade Names
ELIXOPHYLLIN
THEO-DUR
Click for Drug Monograph
levels

Aminoglycosides

Azithromycin Some Trade Names
ZITHROMAX
Click for Drug Monograph

Cephalosporins

Metronidazole Some Trade Names
FLAGYL
Click for Drug Monograph

Penicillins

Sulfonamides

Tetracycline Some Trade Names
ACHROMYCIN V
TETRACYN
TETREX
Click for Drug Monograph

Trimethoprim Some Trade Names
PROLOPRIM
TRIMPEX
Click for Drug Monograph

Phenytoin Some Trade Names
DILANTIN
Click for Drug Monograph

Azole antifungals

Chloramphenicol Some Trade Names
CHLOROMYCETIN
Click for Drug Monograph

Ciprofloxacin Some Trade Names
CILOXAN
CIPRO
Click for Drug Monograph

Isoniazid Some Trade Names
INH
NYDRAZID
Click for Drug Monograph

Macrolides ( erythromycin Some Trade Names
ERY-TAB
ERYTHROCIN
Click for Drug Monograph
, clarithromycin Some Trade Names
BIAXIN
Click for Drug Monograph
, dirithromycin Some Trade Names
DYNABAC

)

Trimethoprim-sulfamethoxazole Some Trade Names

Rifampin Some Trade Names
RIFADIN
RIMACTANE
Click for Drug Monograph
decreases phenytoin Some Trade Names
DILANTIN
Click for Drug Monograph
levels

Aminoglycosides

Cephalosporins

Penicillins

Other fluoroquinolones

Digoxin Some Trade Names
DIGITEK
LANOXIN
Click for Drug Monograph

Azithromycin Some Trade Names
ZITHROMAX
Click for Drug Monograph

Clarithromycin Some Trade Names
BIAXIN
Click for Drug Monograph

Erythromycin Some Trade Names
ERY-TAB
ERYTHROCIN
Click for Drug Monograph

Tetracycline Some Trade Names
ACHROMYCIN V
TETRACYN
TETREX
Click for Drug Monograph

Trimethoprim Some Trade Names
PROLOPRIM
TRIMPEX
Click for Drug Monograph

Aminoglycosides

Cephalosporins

Ketoconazole Some Trade Names
NIZORAL
Click for Drug Monograph

Metronidazole Some Trade Names
FLAGYL
Click for Drug Monograph

Fluoroquinolones

Penicillins

Sulfonamides

*These interfere with vitamin K–dependent clotting factors and may also increase bleeding with antiplatelet drugs and thrombolytics.

Many antibacterials are chemically related and are thus grouped into classes. Although drugs within each class share structural and functional similarities, they often have different pharmacology and spectra of activity.

Selection and Use of Antibacterial Drugs

(See also the Johns Hopkins Point of Care Information Technology Antibiotic Guide.) Antibacterials should be used only if clinical or laboratory evidence suggests bacterial infection. Use for viral illness or undifferentiated fever is inappropriate, subjects the patient to drug complications without any benefit, and contributes to bacterial resistance. Certain bacterial infections (eg, abscesses, infections with foreign bodies) require surgical intervention and do not respond to antibiotics alone.

Cultures and antibiotic sensitivities are essential for selecting a drug for serious infections. However, treatment often must begin before culture results are available, necessitating selection according to the most likely infecting organisms (empiric antibiotic selection). Whether chosen according to culture results or empirically, drugs used should possess the narrowest spectrum of activity that will control the infection. For empiric treatment of serious infections that may involve any one of several pathogens (eg, fever in a neutropenic patient) or that may be due to multiple pathogens (eg, polymicrobial anaerobic infection), a broad spectrum of activity is desirable. The most likely organisms and the organisms' susceptibility to antibacterials vary according to geography (within cities or even within a hospital) and can change from month to month.

Bactericidal drugs kill bacteria in vitro. Bacteriostatic drugs slow or stop in vitro bacterial growth but depend on body defenses to kill bacteria.

Quantitative methods identify the minimum in vitro concentration at which an antibiotic can inhibit growth (minimum inhibitory concentration, or MIC) or kill (minimum bactericidal concentration, or MBC). However, in vivo antibacterial effectiveness involves other factors, including pharmacology (eg, absorption, distribution, concentration in fluids and tissues, protein binding, and rate of excretion or metabolism), the presence of drug interactions or inhibiting substances, and host defense mechanisms. Usually, greater in vitro killing power is important only if local or systemic host defenses are weak (eg, in endocarditis, meningitis, serious infections in neutropenic or other immunocompromised patients).

The predominant determinant of bacteriologic response to antibiotics is either the duration that blood levels of the antibiotic exceed the MIC (time-dependence) or the peak blood level relative to MIC (concentration-dependence). The β-lactams and vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
exhibit time-dependent bactericidal activity. Increasing their concentrations above the MIC does not increase their rate of bactericidal activity, and their in vivo killing is generally slow. In addition, because there is either no or very brief residual inhibition of bacterial growth after concentrations fall below the MIC (postantibiotic effect, or PAE), β-lactams and vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
are most often effective when serum levels of free drug (ie, drug not bound to serum protein) exceed the MIC for 50% of the time. The long serum half-life of ceftriaxone Some Trade Names
ROCEPHIN
Click for Drug Monograph
allows free serum levels to exceed the MIC of very susceptible pathogens for the entire 24-h dosing interval. However, frequent dosing or continuous infusion is required for other β-lactams that have serum half-lives of 2 h. For vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
, trough levels should be maintained at 10 to 15 μg/mL.

Aminoglycosides, fluoroquinolones, and daptomycin Some Trade Names
CUBICIN
Click for Drug Monograph
exhibit concentration-dependent bactericidal activity. Increasing their concentrations from levels slightly above the MIC to levels far above the MIC increases their rate of bactericidal activity and decreases the bacterial load. In addition, after brief exposure to concentrations above the MIC, aminoglycosides and fluoroquinolones exhibit a PAE on residual bacteria, the duration of which is also concentration-dependent. If PAEs are long, drug levels can be below the MIC for extended periods without loss of efficacy, allowing less frequent dosing. Consequently, aminoglycosides and fluoroquinolones are usually most effective as intermittent boluses that achieve peak free serum levels 10 times the MIC of the infecting organism.

Combinations of antibiotics are often necessary in serious infections, either because they provide treatment for multiple possible species of infecting bacteria or because they act synergistically against a single species of bacteria. Synergism is usually defined as more rapid and complete bactericidal action from a combination of antibiotics (usually a cell wall–active agent, ie, a β-lactam or vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
, plus an aminoglycoside) than could be achieved by either antibiotic alone.

Oral administration provides excellent blood levels of many antibiotics and does so nearly as rapidly as IV administration. IV administration is preferred if oral antibiotics cannot be tolerated (eg, due to vomiting) or absorbed (eg, due to malabsorption after intestinal surgery); intestinal motility is impaired (eg, due to opioids); no oral preparation is available (eg, aminoglycosides); or a patient is critically ill, in which case GI tract perfusion may be impaired or even the brief delay with oral administration may be detrimental. Antibiotics should be continued until objective evidence of systemic infection (eg, absence of fever, symptoms, and abnormal laboratory findings) is absent for several days. Courses of therapy for some infections (eg, endocarditis, TB, osteomyelitis) are weeks or months long to prevent relapse.

Doses and scheduling of antibacterials may need to be adjusted in infants, the elderly, and patients with renal failure (see Table 3: Bacteria and Antibacterial Drugs: Usual Doses of Commonly Prescribed Antibiotics Tables). Commonly used antibacterials that need dose adjustment in hepatic insufficiency include cefoperazone, ceftriaxone Some Trade Names
ROCEPHIN
Click for Drug Monograph
, chloramphenicol Some Trade Names
CHLOROMYCETIN
Click for Drug Monograph
, clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
, metronidazole Some Trade Names
FLAGYL
Click for Drug Monograph
, nafcillin Some Trade Names
UNIPEN
Click for Drug Monograph
, and rifampin Some Trade Names
RIFADIN
RIMACTANE
Click for Drug Monograph
. Penicillins, cephalosporins, and erythromycin Some Trade Names
ERY-TAB
ERYTHROCIN
Click for Drug Monograph
are among the safest antibacterials during pregnancy; tetracyclines are contraindicated. Most antibiotics reach sufficient concentrations in breast milk to affect a breastfed baby, sometimes contraindicating their use in nursing women.

Table 3

PDF Usual Doses of Commonly Prescribed Antibiotics 

This table is presented as a PDF and requires the free Adobe PDF reader. Get Adobe Reader

Complications of antibiotic therapy include superinfection by nonsusceptible bacteria or fungi and, commonly, cutaneous, renal, hematologic, and GI adverse effects. Adverse effects frequently require stopping the offending drug and substituting another antibiotic to which the pathogen is susceptible; sometimes, no alternatives exist.

Antibiotic Resistance

Resistance to an antibiotic may be inherent in a particular bacterial species or may be acquired as a result of mutations or acquisition of genes from another organism that encode for antibiotic resistance. Mechanisms for resistance that are encoded by these genes are briefly described in Table 4: Bacteria and Antibacterial Drugs: Common Mechanisms of Antibacterial ResistanceTables. Resistance genes can be transmitted between 2 bacterial cells by transformation (uptake of naked DNA from another organism), transduction (infection by a bacteriophage), or conjugation (exchange of genetic material in the form of either plasmids, which are pieces of independently replicating extrachromosomal DNA, or transposons, which are movable pieces of chromosomal DNA). Plasmids and transposons can rapidly disseminate resistance genes.

Table 4

Common Mechanisms of Antibacterial Resistance

Mechanism

Example

Decreased cell wall permeability

Loss of outer cell wall D2 Porin in imipenem-resistant Pseudomonas aeruginosa

Enzymatic inactivation

Production of β-lactamases that inactivate penicillins in penicillin-resistant Staphylococcus aureus , Haemophilus influenzae , Escherichia coli

 

Production of aminoglycoside-inactivating enzymes in gentamicin Some Trade Names
GARAMYCIN
Click for Drug Monograph
-resistant enterococci

Changes in target

Decreased affinity of penicillin-binding proteins for β-lactam antibiotics (eg, in S. pneumoniae with reduced penicillin sensitivity)

 

Decreased affinity of methylated ribosomal RNA target for macrolides, clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
, and quinupristin in MLSB-resistant S. aureus

 

Decreased affinity of altered cell wall precursor for vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
(eg, E. faecium)

 

Decreased affinity of DNA gyrase for fluoroquinolones in fluoroquinolone-resistant S. aureus

Increased antibiotic efflux pump

Increased efflux of tetracycline Some Trade Names
ACHROMYCIN V
TETRACYN
TETREX
Click for Drug Monograph
, macrolides, clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
, or fluoroquinolones (eg, S. aureus)

Bypass of antibiotic inhibition

Development of bacterial mutants that can subsist on products (eg, thymidine) present in the environment, not just products synthesized within the bacteria (eg, trimethoprim-sulfamethoxazole Some Trade Names

)

MLSB = Macrolide, lincoside, streptogramin B.

Antibiotic use preferentially eliminates nonresistant bacteria, increasing the proportion of resistant bacteria that remain. This is true not only for pathogenic bacteria but also for normal flora; resistant normal flora serves as a reservoir for resistance genes that can spread to future pathogens.

Last full review/revision November 2005

Content last modified November 2005

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