Duration of Antibiotic Therapy: General Principles

2017-07-24 14:40:00
Maricelle O. Monteagudo-Chu, PharmD, BCPS-AQID, and Nageh Shaeishaa, RPH, MSC
Deciding on the duration of antimicrobial therapy for an infection is neither straightforward
nor simple. Most recommendations in infectious disease guidelines are based on either expert
opinions or evidence-based medicine. A short or long course of antibiotics can be given to a
patient, depending on the drug used, the severity of an infection, and response to treatment
(Table 1).

Although antibiotics are, in general, safe, they also have many risks associated with their use,
including the development of allergic reactions, Clostridium difficile infection, and antibiotic
resistance, as well as a higher price tag. As such, many clinicians prefer prescribing a shorter
treatment course. However, it also is important to provide a substantial treatment course so
that an infection is treated adequately and relapse is prevented. This article is a review of the
general principles for setting optimal antibiotic durations of therapy.

CHOICE OF AGENT
Antibiotics work by either selectively killing (bactericidal) or inhibiting the growth
(bacteriostatic) of bacteria. Infections with a high bacterial burden, such as those seen in
infective endocarditis, require treatment with antibiotics with rapid bactericidal activity. In
most cases, more than 1 antibiotic is used to provide synergistic activity and rapid killing. For
example, when treating native valve endocarditis caused by penicillin-susceptible viridans
streptococci, the usual treatment duration can vary from 2 to 4 weeks. If penicillin G or
ceftriaxone monotherapy is prescribed, the treatment duration should be 4 weeks; however, if
either antibiotic is used in combination with an aminoglycoside, then the treatment can be
shortened by 2 weeks.11
Another factor that can affect the efficacy of antibiotics is their ability to penetrate and
remain (for an adequate time) at the site of infection. Fosfomycin tromethamine, quinolones,
nitrofurantoin, trimethoprim-sulfamethoxazole and beta-lactams are some of the antibiotics
used to treat urinary tract infections. Even though these antibiotics can concentrate well in the
genitourinary tract, each can differ in duration of treatment. For example, fosfomycin can be
given in a 1-time dose because a single 3-g oral dose can provide a peak urinary
concentration within 4 hours and remain elevated (>128 mg/L) for ≤48 hours.12 In another
example, Hooton et al found that a 3-day course of cefpodoxime proxetil, a third-generation
cephalosporin, did not provide a similar cure rate as it did with a 3-day regimen of
ciprofloxacin (cure rate, 82% vs 93%, respectively; 95% CI, 3%-18%) for the treatment of
acute uncomplicated cystitis.13

TYPE AND SEVERITY OF INFECTION

A patient’s immune status, affected anatomical site, and pathogen causing the infection also
should be considered when assessing duration of therapy. Infected patients with no
hemodynamic issues can be treated with short courses of antimicrobials. For example,
community-acquired pneumonia (CAP) can be treated in as little as 5 days, but once the
patient’s condition is complicated by bacteremia or severe sepsis, a longer course of
antibiotics is essential.3

The ability of antibiotics to penetrate necrotic tissues, abscesses, or biofilms also can limit
their efficacy. Infections can be difficult to treat and require prolonged antibiotic courses.
Unless surgical intervention is undertaken to remove debris and/ or drain abscesses,
antibiotics cannot reach infected sites. For example, a course of antibiotics for intraabdominal
infections is no longer than 7 days; however, if it is difficult to perform the source control
procedure (eg, drain infected foci, control ongoing peritoneal contamination), a longer
treatment course is necessary.8

ASSESSMENT OF PATIENT’S RESPONSE

Improvements in hemodynamic status (eg, heart rate, blood pressure), white blood cell count,
temperature, oxygenation, and/or radiologic findings should be seen a few days after starting
an effective therapy. Once the signs and symptoms of infections are resolved, clinicians can
consider terminating therapy. El Moussaoui et al conducted a randomized, double-blind,
placebo-controlled study comparing the effectiveness of discontinuing amoxicillin therapy in
mild to moderate-severe CAP after 3 days compared with 8 days.14 Patients were assessed
regarding4 respiratory symptoms (dyspnea, cough, sputum production, color of sputum) and
general improvement (not recovered to complete recovery) based on a 5-point symptom
scale. Patients who improved by ≥2 points, who had a temperature <38°C, and who were able
to take oral medications were randomized to receive either 750-mg oral amoxicillin or
placebo for 3 to 5 days. They found that discontinuing antibiotics 3 days after symptom
resolution did not adversely affect patient outcomes. In addition, there were no differences in
clinical or radiological outcomes between the 2 groups after 10 days and 28 days.14

Rechecking for cultures is not always necessary once a patient begins responding to therapy,
except in the case of bloodstream infections. Monitoring for bacterial clearance is crucial
because day 1 of antimicrobial therapy is the first day on which negative blood cultures are
obtained.15 Acquiring unnecessary cultures should be avoided because a positive culture
having no signs and symptoms of infection could lead to treating colonized bacteria.

The use of biomarkers, such as C-reactive protein (CRP), and the procalcitonin test also has
been instrumental in evaluating antibiotic response and determining the duration of antibiotic
therapy. Unlike CRP, procalcitonin is more specific to bacterial infections; therefore, the test
has been used to curtail unnecessary antibiotic usage. Use of the procalcitonin-guided
algorithm has been shown to reduce the duration of exposure to antibiotics by ≤25% in
patients with lower respiratory tract infections16 and 23% in patients who are critically ill.17

CONCLUSION
Pharmacists are vital team members in antibiotic stewardship. Thus, they should have a good
understanding of the ways in which antibiotics work and the factors that affect their efficacy.
In addition, they must be able to monitor for responses to antibiotics to ensure that patients
are treated adequately and infection relapses are prevented.