COMMENTARY

Infectious Diseases: February 15, 2004

John Bartlett, MD

Disclosures

February 17, 2004

In This Article

Antimicrobial Therapy

Zwart S, Rovers MM, de Melker RA, Hoes AW. Penicillin for acute sore throat in children: randomized, double blind trial. BMJ. 2003;327:1327-1328. This is a report from The Netherlands involving children aged 4-15 years who contacted a participating general practitioner for a sore throat of less than 7 days' duration and had at least 2 of the 4 Centor criteria, which include history of fever, absence of cough, swollen cervical lymph nodes, and tonsillar exudate. Participants were randomized to receive penicillin V for 7 days, penicillin V for 3 days, or placebo. The patients had throat cultures at baseline and at 2 weeks for detection of group A streptococci. There were 156 participants with a mean age of 10 years and a mean duration of symptoms of 3.8 days. Throat cultures were positive in 96 of the 156 patients (62%). The results showed no difference in clinical outcome for the 3 groups in terms of time to resolution of symptoms or duration of school absence. This applied to the 3 groups in total and in the subset with group A streptococcal infection. There were 11 streptococcal sequelae, including quinsy in 9, scarlet fever in 1, and impetigo in 1. Eight of these occurred in the group that received placebo, although this difference was not statistically significant. The only statistically significant difference in the 3 treatment groups was the rate of eradication of group A strep, which was 68% in the group that received penicillin for 7 days and 28% in the placebo group. These results are summarized in Table 1 .

The authors conclude that penicillin had no clear benefit in children with a sore throat in terms of the duration of symptoms, but penicillin may reduce the frequency of streptococcal sequelae.

Comment: The authors claim that this is the first randomized, double-blind, placebo-controlled trial of penicillin treatment of pharyngitis in children. Their conclusion is that general practitioners should use penicillin to treat pharyngitis "only when they are severely ill (unable to drink or imminent quinsy) or at high risk (history of rheumatic fever, having an anatomical or immunological disorder, high incidence of streptococcal infection in the community)." This strategy would virtually eliminate the need for throat cultures or rapid antigen tests, which are currently advocated. Two Centor criteria were used as the criteria for inclusion, but this was supplemented with throat cultures. The recommendations for management of adults with group A strep from the Centers for Disease Control and Prevention (CDC) advocates empiric penicillin therapy in patients with 3 or 4 of the Centor criteria.[1] These CDC criteria were not accepted in the guidelines for management of pharyngitis in adults by the Infectious Diseases Society of America (IDSA) due to concerns about the high frequency of false-positive results with Centor criteria as a surrogate for group A strep[2].

An unusual and disappointing feature of the study was the randomization to treatment for 3 days or 7 days; the standard treatment period has traditionally been 10 days, and this is the current recommendation by the IDSA, the CDC, and the American College of Physicians in each of their respective guidelines. There is 1 additional facet of strep pharyngitis that is not addressed in body of the report or in the conclusions: the concern about potential transmission by children. This may be an important reason to treat that was not assessed in this study. Nevertheless, the only statistically significant difference in the 2 groups shown in The Netherlands study was the rate of eradication of group A strep that was anticipated, and this may be a salutary benefit that is underappreciated in terms of epidemiologic significance. One additional concern is the trend toward complications that clearly favored penicillin treatment with established strep infection, but the differences were not statistically significant; this difference may simply reflect sample size.

Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350:11-20. The authors performed a prospective, randomized, placebo-controlled trial of valacyclovir (500 mg/day for 8 months) in 1484 immunocompetent, heterosexual, monogamous couples that were discordant for herpes simplex virus-2 (HSV-2) symptomatic genital infection. A subset analysis was done in 89 patients to determine the effect of valacyclovir on viral shedding using HSV polymerase chain reaction (PCR) analysis of genital swab specimens. The results were analyzed by the number of symptomatic genital infections in the source patient, by the number of newly acquired genital infections in the partner who was negative at baseline, and by the percent days of viral shedding. The results are shown in Table 2 .

The authors conclude that valacyclovir given once daily to a patient with genital herpes significantly reduces the rate of HSV transmission.

Comment: The potential value of acyclovir or valacyclovir and related agents to prevent clinical episodes of genital herpes is well established. The importance of this study was the demonstration that this suppression, not surprisingly, also prevents transmission to sexual partners. The biological reason is not rocket science: as demonstrated in the study, viral shedding is notably reduced in the source patient. The potential application of this information is important for couples who are discordant for HSV. However, as noted in the editorial by Clyde Crumpacker,[3] this may have even more important application for reducing transmission of HIV infection. HSV is the leading cause of genital ulcers in both developed and developing countries. These ulcers have high concentrations of HIV in coinfected patients.[4] In terms of the practical application of these data, the obvious concern might be the expense, safety, and concern for resistance. A recent report of HSV isolates from genital lesions in 2088 patients attending STD clinics showed that only 0.2% were resistant to acyclovir.[5] The safety profile of these drugs is well established by the extensive use of acyclovir (the drug has been used in millions since it was introduced in 1982). In terms of cost, Dr. Crumpacker notes that generic acyclovir at 400 mg twice daily costs about $73/year.

Zervos MJ, Hershberger E, Nicolau DP, et al. Relationship between fluoroquinolone use and changes in susceptibility to fluoroquinolones of selected pathogens in 10 United States teaching hospitals, 1991-2000. Clin Infect Dis. 2003;37:1643-1648. The study presents data on the fluoroquinolone sensitivity of 11 major bacteria obtained from 10 hospitals with 381-1389 beds for the period from 1991 to 2000. Fluoroquinolone use was defined as the number of daily doses/1000 patient-days. The median was 85, but the range was 15 to 725. With regard to susceptibility, there was a significant decrease in 6 of the 11 organisms analyzed, and the change in percent susceptible was significantly correlated with fluoroquinolone use (P = .05). With regard to susceptibility, the change noted over the course of the study is summarized in Table 3 .

The authors conclude that decreasing sensitivity of Staphylococcus aureus and multiple gram-negative bacilli are associated with fluoroquinolone use and that efforts should be made to limit their use to those infections in which these drugs appear to have a benefit when compared with alternatives.

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