Principles of antibiotic therapy

Host factor Special antibiotic concern

Drug allergy

Site of infection


Epidemiologic information

Renal function

Recent antibiotic exposure

Infection acquisition (community/ECF/hospital)

Concomitant medication

Safety record

Success record

Most likely organism(s) and susceptibility


Penetration into privileged sites (CNS, endocardium)

Potential to cause major untoward event

Abbreviations: CNS = central nervous system; ECF = extended care facility.

Antibiotic combinations are sometimes used to manage selected infections (Table 205.2). There are potential disadvantages, however, to the administration of antibiotic combinations such as increased untoward events, heightened costs, and suprainfection.

Table 205.2 Combination therapy

Disseminated Mycobacterium avium complex
Helicobacter pylori
Endocarditis (α-hemolytic streptococcus, enterococcus)
Life-threatening infection caused by Pseudomonas aeruginosa
Empiric treatment

-Pneumococcal meningitis until susceptibility confirmed

-Febrile, severely neutropenic host

-Polymicrobic infection

-Life-threatening infection with inapparent source

Practice guidelines and antibiotic stewardship

In the past, with few exceptions, choosing an antibiotic has been left to the whims of clinicians. Seldom has the optimal duration of antibacterial treatment been defined by evidence-based medicine. Practice guidelines have emerged in response to questions regarding the quality, consistency, and the expense of medical care. Guidelines are generally created based upon the best available scientific evidence melded with expert opinion, cohesively assembled in a usable format for practitioners. Selected medical societies and organizations, as well as easily accessible websites, have become the repositories for the recommended information. Access to these guidelines has helped to transform how medicine is practiced today. Guidelines for various infectious conditions already exist, whereas others are being created and refined.

Just as important as the guidelines has been the recognition of the need for optimal, cost-effective, and rational use of antibiotics. Stewardship has evolved from guidelines to encompass antimicrobial utilization for all conditions and can be found in hospitals, long-term care facilities, long-term acute care facilities, ambulatory surgical centers, dialysis centers, and other medical settings. Institutions employing stewardship are coordinating interventions, often in conjunction with pharmacy assistance, to promote appropriate antibiotic selection, as well as their proper dose, duration, and route of administration. Benefits of antibiotic stewardship include improved clinical outcomes, reduced medical costs, fewer toxic and adverse effects, and decreased selection of antibiotic-resistant microorganisms.

Special populations

The pregnant patient

Physiologic changes in the urinary tract and complications of parturition predispose the pregnant woman to urinary tract infections, as well as chorioamnionitis and endometritis. Antibiotic selection for the pregnant woman must take into consideration the potential for drug-induced toxicities for both the woman and her developing fetus. Animal studies and epidemiologic data (generated from pregnant women who were exposed to antibacterial agents because of clinical need) suggest that penicillins, including those in combination with a β-lactamase inhibitor, cephalosporins, aztreonam, erythromycin, azithromycin, clindamycin, and metronidazole have not demonstrated human fetal risk. Sulfonamides should be avoided late in pregnancy because of the potential to develop neonatal kernicterus. Chloramphenicol should not be administered to the mother near term as the newborn does not possess the appropriate liver enzyme to metabolize this drug, and hence the “gray baby” syndrome can result. The aminoglycosides gentamicin, tobramycin, and amikacin should not be administered to pregnant women, especially eclamptic women, unless there is a compelling reason. If they must be prescribed, serum concentrations must be monitored carefully.

The fluoroquinolones are not recommended for use in pregnancy because of their adverse effects on developing cartilage seen in animal studies. Tetracyclines are contraindicated in pregnant women because these compounds can interfere with normal development of teeth and bones in the fetus and have caused hepatorenal failure and death, particularly when administered intravenously to treat pyelonephritis, in pregnant women.

The elderly patient

There are a number of factors that distinguish the administration of antibiotics in elderly patients: concern about compliance with the medication because of poor memory, impaired vision, diminished hearing, or difficulty in opening child-resistant containers; the decrease of renal function with normal aging, and the need to make appropriate dosage adjustment of medications to prevent antibiotic-related toxicities; the potential for drug–drug interactions, as many geriatric patients take numerous medications daily; and the presence of concomitant medical disorders that can adversely influence antibiotic distribution and penetration. Elderly patients appear to experience adverse drug reactions from antibacterial compounds more frequently than younger patients do (Table 205.3).

Table 205.3 Adverse drug reaction

Drug Untoward event
Aminoglycoside Nephrotoxicity, ototoxicity
Amoxicillin–clavulanate (chronic administration) Hepatotoxicity
TMP–SMX Blood dyscrasias, hyperkalemia
Fluoroquinolone Seizure
Doxycycline Esophageal stricture/ulcer
Nitrofurantoin (chronic administration) Pulmonary fibrosis, hepatitis, agranulocytosis

Abbreviation: TMP–SMX = trimethoprim–sulfamethoxazole.

Antibiotic use in continuous renal replacement therapy

For critically ill patients with infection, acute renal insufficiency often develops. Acute renal failure is associated with increased morbidity and mortality in patients with sepsis. Continuous renal replacement therapy (CRRT), an alternative to traditional hemodialysis and better tolerated by hemodynamically unstable patients, decreases the incidence of adverse biomarkers. Appropriate dosing of antimicrobial agents for patients receiving CRRT remains poorly defined, as the pharmacokinetics of drug removal in critically ill patients undergoing CRRT is complex. Those antibiotics with low protein-binding capacity and/or poor tissue penetration have enhanced removal. Mechanical or operational factors associated with CRRT play a role in antibiotic therapy in these patients as well, and increasing the blood flow or dialysate flow rate of CRRT may increase drug clearance. Tables 205.4 and 205.5 list antibiotic dose alterations for patients with CRRT.

Table 205.4 Drugs not requiring dosage alteration during continuous renal replacement therapies
















Table 205.5 Drugs requiring dosage alteration during CRRTa















a Dose reduction as compared to normal renal function.

Abbreviations: CRRT = continuous renal replacement therapies; TMP–SMX = trimethoprim–sulfamethoxazole.

Route of administration

Antibiotics are administered intravenously when the patient has systemic perfusion issues (septic shock, hypotension), has bacterial infection at a

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Jun 18, 2016 | Posted by in INFECTIOUS DISEASE | Comments Off on Principles of antibiotic therapy

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