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Infectious Diseases Update
Abstracts of current literature on epidemiology, diagnosis, and treatment
Series Editor: Jihad Slim, MD
HIGH-DOSE AZITHROMYCIN MORE EFFECTIVE FOR
GROUP A STREPTOCOCCAL TONSILLOPHARYNGITIS
Investigators performed a meta-analysis of 19 randomized controlled trials that compared azithromycin with a 10-day course
of other antibiotics for treatment of group A streptococcal
(GAS) tonsillopharyngitis in children (14 trials) and adults
(5 trials) to determine the optimal dose of azithromycin for
treating these patients (N = 4626). The primary outcome was
bacteriologic cure, defined as failure to isolate GAS from throat
culture after therapy completion; the secondary outcome was
clinical cure, defined as the absence of GAS on throat culture
and symptom/sign resolution or improvement after therapy
completion and follow-up. The comparative drugs were 6 antibiotics, most frequently penicillin (10/19 trials). Azithromycin
total dose was either 30 or 60 mg/kg/d for children and either
500 mg on day 1 with 250 mg on days 2 through 5 (4 trials) or
500 mg on day 1 with 500 mg on days 1 through 3 (15 trials) for
adults. In pediatric trials, a 60-mg/d dose of azithromycin was
superior to the comparative antibiotic, the 30-mg/d dose of
azithromycin was inferior to the comparative antibiotic, and the
3-day regimen was inferior to the 5-day regimen. No adult studies compared dosages by weight. In adult trials, the 5-day azithromycin regimen was inferior to the 10-day comparative antibiotic, but the 3-day dose (the same total dose as the 5-day
regimen) achieved a better outcome than the comparative antibiotic. This review suggests that azithromycin administered at a
dose of 60 mg/kg/d in children or administered for 3 days at a
dose of 500 mg/d in adults is more effective than other treatment regimens for GAS tonsillopharyngitis.
Casey JR, Pichichero ME. Higher dosages of azithromycin are more
effective in treatment of group A streptococcal tonsillopharyngitis. Clin
Infect Dis 2005;40:1748–55.
ANTIBIOTIC PROPHYLAXIS IN NEUTROPENIC PATIENTS
Researchers conducted a meta-analysis of 95 randomized controlled trials performed from 1973 to 2004 to determine
whether mortality and infection decreased after antibiotic prophylaxis in afebrile neutropenic patients (N = 9283). Trials compared different antibiotics, antibiotics with placebo, or antibiotic
treatment without intervention: 50 trials compared a prophylactic antibiotic with placebo or without intervention (including
17 trials comparing 5 different types of fluoroquinolones), and
45 trials compared different prophylactic regimens (including
30 trials comparing fluoroquinolones with other antibiotics and
5 trials comparing different fluoroquinolones). The primary
outcome was all-cause mortality by the end of each study’s
follow-up; secondary outcomes were infection-related death,
fever, clinically or microbiologically documented infection, bac-
teremia, adverse effects, and emergence of resistant bacteria.
Prophylaxis was started either after neutropenia developed
(17 trials) or with chemotherapy initiation (78 trials). Compared
with placebo or without treatment, antibiotic prophylaxis and
specifically fluoroquinolone prophylaxis significantly decreased
mortality risk, infection-related death, fever, clinically or microbiologically documented infections, gram-negative and -positive
infections, and bacteremia but caused more adverse events. In
addition, fluoroquinolones increased the risk for drug resistance. Prophylaxis with antibiotics, particularly fluoroquinolones,
reduces mortality for neutropenic patients, which outweighs
detriments such as cost, adverse effects, and development of
drug resistance.
Gafter-Gvili A, Fraser A, Paul M, et al. Meta-analysis: antibiotic
prophylaxis reduces mortality in neutropenic patients. Ann Intern
Med 2005;142:979–95.
POOR OUTCOME WITH METRONIDAZOLE FOR
CLOSTRIDIUM DIFFICILE COLITIS
The authors performed a prospective, observational study of 207
patients treated with metronidazole for Clostridium difficile colitis
to examine treatment failure and infection recurrence rates. All
patients had a positive result on fecal enzyme-linked immunosorbent assay for C. difficile toxin and were treated with metronidazole (≥ 1.5 g/d) for at least 7 days. Patients’ response to treatment
was as follows: (1) complete response (103 [50%] patients), with
resolution of C. difficile colitis 9 days or fewer after starting treatment and no infection recurrence for 3 months; (2) refractory
to treatment (46 [22%]), with disease signs/symptoms persisting
for 10 days or more after treatment initiation; (3) documented
recurrence (58 [28%]), with disease signs/symptoms recurring
within 90 days after initial clinical response and C. difficile toxin
noted in feces; or (4) clinical recurrence (11 [5%]), with disease
signs/symptoms recurring within 3 months after initial clinical
response and without documentation of C. difficile toxin. During
treatment and the subsequent 90 days, 27% of 207 patients died;
mortality was 33% for patients who did not respond to therapy
and 21% for patients who were cured of C. difficile infection.
Based on the relatively poor response to metronidazole, researchers concluded that new treatments and prevention for
C. difficile infection must be sought.
Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after
treatment of Clostridium difficile colitis with metronidazole. Clin
Infect Dis 2005;40:1586–90.
Dr. Slim is an assistant professor of medicine, Seton Hall University, South
Orange, NJ. Abstracts written by Deanna Laing, ELS, for Hospital Physician.
Copyright 2005 by Turner White Communications Inc., Wayne, PA. All rights reserved.
www.turner-white.com
Hospital Physician August 2005
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