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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 Bacteria). 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 Interactions.

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 ). 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
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 Resistance. 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