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The principles involved in the choice of antibiotic selection for particular conditions have all been outlined and discussed in the previous parts of this chapter. It is critical that all factors are considered.

The causal bacterium: its nature and characteristics

 The host: sex (and pregnancy status), age, general and particular health status, liver function, renal function, allergies.

 Drug factors: antibacterial spectrum, resistant organisms, pharmacodynamics (blood concentrations, how high and for how long), pharmacokinetics (metabolism and excretion). As an example, two patients infected with the identical organism may require different antibiotics because of:

o Differences in the site of infection. o Drug allergies.

o Underlying illness. o Concomitant drug therapy. o Age.

o Pregnancy.

In the absence of allergies, pregnancy, other underlying illness and potential drug interactions, there are often

accepted antibiotics of choice for common bacterial infections. The appropriate antibiotic choices for selected common pathogens are presented in Table 6.19.

ADVERSE EFFECTS OF ANTIBIOTICS

 Nearly all can cause Clostridium difficile enteritis

 Aminoglycosides can cause irreversible aplastic anemia and the gray baby syndrome  Sulfonamides can cause a skin rash, Stevens-Johnson syndrome, and toxic

epidermal necrolysis

 Tetracycline can discolor the teeth if given to children under 8 years of age

Table 6-19. Drugs of choice and alternatives for selected common bacterial pathogens

Bacterium Drug(s) of choice Alternatives Comments

Streptococcus species Penicillin A first-generation

cephalosporin Some strains are penicillin-resistant, especially a growing proportion of S.

pneumoniae

Erythromycin Erythromycin is only for mild infections

Clindamycin Vancomycin is only for serious infections

Vancomycin Certain fluoroquinolones are active against S. pneumoniae

Enterococcus species Penicillin or ampicillin

plus gentamicin Vancomycin plus gentamicin There are some strains for which streptomycin is synergistic but gentamicin is not

Quinupristin-

dalfopristin Some strains are resistant to synergy with any aminoglycoside Linezolid Some strains are resistant to

vancomycin (VRE)

Staphylococcus

species An antistaphylococcal penicillin A first-generation cephalosporin Vancomycin is required for methicillin-resistant strains Vancomycin Rifampin is occasionally used to

eradicate the nasal carriage state

Neisseria meningitidis Penicillin A third-generation

cephalosporin Chloramphenicol

Rare strains are penicillin-resistant

Neisseria gonorrhoeae Cefixime Ciprofloxacin

A third-generation cephalosporin

Some strains are fluoroquinolone- resistant (especially in Asia)

Bordetella pertussis Erythromycin TMP-SMZ

(trimethoprim- sulfamethoxazole)

Other macrolides are also active in vitro

Pasteurella multocida Penicillin A first-generation cephalosporin Haemophilus influenzae Aminopenicillin Cefuroxime A third-generation cephalosporin Chloramphenicol Approximately 30% are aminopenicillin-resistant; therefore aminopenicillins should not be used empirically in serious infections until susceptibility results are available Rifampin is used to eradicate the nasal carriage state

Enterobacteriaceae in

urine TMP-SMZ Ciprofloxacin Gentamicin β Lactams are less effective than TMP-SMZ or fluoroquinolones for the treatment of urinary tract infection

Enterobacteriaceae in cerebrospinal fluid

A third-generation cephalosporin

Meropenem In neonates only, aminoglycosides are equivalent to third-generation cephalosporins

TMP-SMZ Experience with TMP-SMZ in

Enterobacteriaceae elsewhere (blood, lung, etc.) Gentamicin or a third- generation cephalosporin or ciprofloxacin

TMP-SMZ Two-drug therapy is sometimes used in serious infection

Carbapenems Monotherapy with a third-generation cephalosporin should be avoided if the pathogen is Enterobacter

cloacae, E. aerogenes, Serratia marcescens or Citrobacter freundii

Pseudomonas aeruginosa Antipseudomonal penicillin plus aminoglycoside Ceftazidime Ciprofloxacin A carbapenem

Two-drug therapy recommended except for urinary tract infection

Bacteroides fragilis Metronidazole or

clindamycin A carbapenem A penicillin β lactamase inhibitor

B. fragilis is usually involved in

polymicrobial infections; therefore another antibiotic active against Enterobacteriaceae is often required

Mycoplasma pneumoniae

A macrolide (e.g.

erythromycin) A tetracycline Although tetracyclines are as effective as macrolides, the latter are recommended because of better activity against Pneumococcus, which can mimic this infection

Ureaplasma urealyticum

A tetracycline Erythromycin A few strains are tetracycline- resistant

Mycoplasma hominis A tetracycline Clindamycin Erythromycin is not active against M. hominis

Chlamydia trachomatis

A tetracycline Azithromycin Azithromycin is the only therapy effective in a single dose

Erythromycin Erythromycin is used in pregnancy Rickettsial species A tetracycline Chloramphenicol

Listeria monocytogenes Ampicillin plus gentamicin Vancomycin plus gentamicin

Legionella species A macrolide A tetracycline

A fluoroquinolone Rifampin is occasionally used as a second agent in severe cases

Clostridium difficile Metronidazole Vancomycin (oral) Mycobacterium

tuberculosis

Isoniazid plus rifampin Streptomycin Directly observed therapy (DOT) is recommended

plus pyrazinamide A fluoroquinolone Isoniazid is used alone for treatment of latent tubercular infection

plus ethambutol Ethionamide

Cycloserine

Viomycin

Capreomycin

Mycobacterium avium

complex Clarithromycin plus ethambutol ± rifabutin Ciprofloxacin Amikacin

Mycobacterium leprae Dapsone plus rifampin

± clofazimine Clarithromycin Thalidomide is useful for erythema nodosum leprosum

FURTHER READING

Akins RL, Haase KK. Gram-positive resistance: pathogens, implications, and treatment options: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2005; 25: 1001-1010.

Boffito M, Acosta E, Burger D et al. Therapeutic drug monitoring and drug-drug interactions involving antiretroviral drugs. Antivir Ther 2005; 10: 469- 477.

Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: An advisory statement from the National Surgical Infection Prevention Project. Clin

Infect Dis 2004; 38: 1706-1715. [Guidelines for the use of antibiotics in surgery.] Dando TM, Perry CM. Related Enfuvirtide. Drugs 2003; 63: 2755-2766.

Fraaij PL, van Kampen JJ, Burger DM, de Groot R. Pharmacokinetics of antiretroviral therapy in HIV-1-infected children. Clin Pharmacokinet 2005;

44: 935-956.

MacDougall C, Polk RE. Antimicrobial stewardship programs in health care systems. Clin Microbiol Rev 2005; 18: 638-656. Medical Letter Choice of antibacterial drugs: Treatment guidelines. Med Let 2004; 2: 13-26.

Onyebujoh P, Zumla A, Ribeiro I et al. Treatment of tuberculosis: present status and future prospects. Bull World Health Organ 2005; 83: 857-865 [A world view of the problem of tuberculosis and its treatment with drugs.]

Rom WN, Gray SM eds. Tuberculosis: 2nd Edition. Lippincott, Williams [amp ] Wilkins, Philadelphia, 2004 [The definitive and current text on tuberculosis and its treatment with drugs with individual chapters on different antitubercular drugs.]

Shefet D, Robenshtok E, Paul M, Leibovici L. Empirical atypical coverage for inpatients with community-acquired pneumonia: systematic review of randomized controlled trials. Arch Intern Med 2005; 165: 1992-2000.

USEFUL WEBSITES

http://www.cdc.gov/drugresistance/healthcare. [This site is a useful one for obtaining current information regarding resistance to antibiotics.]

http://www.nlm.nih.gov/medlineplus/antibiotics.html [Provides general information regarding bacteria and antibiotic drugs.]

PART 4

DRUGS AND FUNGI

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