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July 2008
Volume 18, Number 7
IDSA Journal Club, July 2008

In this feature, a panel of IDSA members identifies and critiques important new infectious diseases studies in the current literature that have a significant impact on the practice of infectious diseases medicine.


 Antibiotic Prophylaxis Does Not Reduce Pyelonephritis Recurrence

Jason Weinberg, MD

In the June issue of Pediatrics, Pennesi and colleagues demonstrate that continuous antibiotic prophylaxis does not reduce the rate of pyelonephritis recurrence or the incidence of renal damage in young children with vesicoureteral reflux.

Long-term antibiotic prophylaxis is frequently prescribed for young children with reflux despite the lack of good data showing that this intervention reduces the incidence of recurrent acute pyelonephritis or prevents renal scarring.  In this multicenter, randomized, controlled trial, 100 children with grade II, III, or IV vesicoureteral reflux were randomized either to receive prophylaxis or no intervention for two years; all children were then followed for an additional two years without prophylaxis.  There were no differences between groups in the risk for having pyelonephritis recurrence or renal scarring.

While not particularly large, the study has the benefit of focusing on the at-risk population of children between 1 and 30 months.  The investigators used a standardized agent (sulfamethoxazole/trimethoprim) for prophylaxis; unfortunately, no placebo was used in the control group.  Patients and investigators were not blinded to the treatment assignment, but objective follow-up with renal ultrasound, voiding cystourethrogram and DMSA scans was performed by radiologists who were blinded to treatment condition.  The microbiology of recurrent pyelonephritis episodes was well-defined, leading to the interesting finding that recurrences in the prophylaxis group tended to be associated with bacteria resistant to multiple antibiotics, whereas all recurrences in the control group were caused by bacteria sensitive to all antibiotics tested.

The jury is still out on prophylaxis for children with grade V reflux, but it is increasingly clear that long-term antibiotics are not necessary for most young children who have reflux diagnosed after an episode of pyelonephritis.  (Pennesi et al.  Pediatrics 2008;121:e1489-94.)

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 Sequential Therapy Superior Against H. pylori

Sara Cosgrove, MD

Ten-day sequential therapy, in which patients receive five days of a proton pump inhibitor (PPI) and one antibiotic followed by five days of a PPI and two other antibiotics, appears superior to standard seven-to-10 day triple therapy for Helicobacter pylori infection in treatment-naïve patients, according to a meta-analysis published in the June 17 Annals of Internal Medicine

The meta-analysis examined 10 randomized controlled trials that included 1,363 patients who received sequential therapy and 1,384 who received standard therapy.  All patients had not received agents used to treat H. pylori in the preceding month; had the diagnosis of H. pylori made via histologic evaluation, biopsy urease test, fecal antigen test, or urea breath test; and had a test of cure using one of these tests at least one month following therapy. Pooled crude eradication rates were 93.4 percent in the sequential therapy group and 76.9 percent in the standard therapy group. Reported adherence rates in both groups were greater than 90 percent in eight of 10 studies.

This meta-analysis has some limitations. Most notably, all of the studies were performed in Italy, which may affect generalizability. Only one of 10 studies was double-blinded. Also, some guidelines consider standard therapy to be a 14-day course rather than 10 days.  However, given the declining rates of H. pylori eradication in the United States using standard therapy, alternative approaches such as sequential therapy should be seriously considered and studied. (Jafri et al., Ann Intern Med. 2008;148:923-31.)

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 Single-tier Lyme Disease Test May Reduce Misdiagnosis

Melinda Pettigrew, PhD

In the first prospective study of two diagnostic tests for Lyme disease, the single-tier IgG VlsE C6 peptide ELISA test performed as well as the CDC-recommended two-tiered IgM and IgG ELISA and Western blot method in patients with symptoms of disseminated or late Lyme disease. An accompanying editorial notes that given the frequency with which the two-tier test is misinterpreted in clinical practice, the single-tier test has the potential to reduce misdiagnoses of Lyme disease. The study and editorial appear in the July 15 issue of Clinical Infectious Diseases,

Steere and colleagues prospectively examined the performance of the two-tiered test and the C6 peptide ELISA among patients with different stages of Lyme disease, patients with other illnesses, and in healthy controls. The sensitivity of both tests was very low among patients with the erythema migrans rash, which is present in a majority of early Lyme patients. Both tests performed well among patients in the later stages of disease.

The two-tiered test had slightly higher specificity and when used correctly can potentially provide information regarding the estimated duration of infection. However, problems persist with the correct interpretation and appropriate use of the two-tiered test in clinical practice. The C6 peptide ELISA may allow for ease of use and standardization of testing. Thus, this test has the potential to decrease the number of misdiagnosed cases of Lyme disease. This study was conducted in a controlled research laboratory setting. It remains to be seen how the C6 peptide ELISA would perform in clinical practice.

(Steere et al., Clin Infect Dis. 2008; 47:188-95; commentary by Weinstein, Clin Infect Dis. 2008;47:196-7.)

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 Waiting-room Video May Help Prevent Sexually Transmitted Diseases

Melinda Pettigrew, PhD

An STD prevention intervention that involved playing a short video containing safe sex messages to patients in the waiting rooms of public STD clinics resulted in a 10 percent decrease in the incidence of new STDs, as described in the June 24 issue of PLoS Medicine. The “Safe in the City” intervention video was played in STD clinic waiting rooms on alternate months. The control group consisted of the usual waiting room environment, without the video. Incident cases of laboratory-confirmed STDs were determined during the follow-up period by medical record review and county surveillance registries. Subjects were assigned to the intervention or control group based on whether their first clinic visit took place during an intervention or control four-week period. The intervention was most effective among men, older patients, and those who had an STD at their first visit.

A video intervention should be simple and affordable to implement, and has the potential to reach a large number of people. These data are likely to be generalizable since the study was conducted under real-world waiting room conditions. More research is needed to identify the specific aspects of the video that are most effective and to identify interventions that will be effective in preventing STDs in women. (Warner et al., PLoS Medicine. 2008;5:e135.)

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 Acyclovir Does Not Prevent HIV Acquisition in HSV-2-infected Patients

Khalil Ghanem, MD

Two recent randomized controlled trials demonstrated that acyclovir did not reduce HIV acquisition among herpes simplex virus 2 (HSV-2)-infected patients. This is disappointing news given the high prevalence of HSV-2 infection around the world and the strong epidemiologic data linking HSV-2 with increased acquisition of HIV.

In the first trial, published in the April 10 issue of the New England Journal of Medicine, 821 women who were HIV-negative and HSV-2-seropositive were randomized to receive 400 mg of acyclovir twice daily or placebo. The women were followed for 12 to 30 months. Despite a median adherence of 90 percent to the study drug, there was no overall effect of acyclovir on the incidence of HIV (rate ratio for the acyclovir group: 1.08; 95 PE confidence interval: 0.64 to 1.83).  Of note, acyclovir did not decrease the rates of genital ulcer disease in the intervention group. (Watson-Jones et al., NEJM. 358:1560-1571.)

The second study, published in the June 21 issue of the Lancet, recruited 1,814 men and 1,358 women. The study design was similar to the first study. Again, despite 94 percent adherence to the study drugs, there was no overall effect of acyclovir on the incidence of HIV (hazard ratio for the acyclovir group: 1.16; 95 percent confidence interval, 0.83 to 1.62). In the latter study, however, acyclovir did decrease the rates of genital ulcers by 47 percent. (Celum et al., Lancet. 2008;371:2109-2119.)

After the success of circumcision in reducing HIV acquisition in men and the recent disappointment in a preventive HIV vaccine, there was great hope that HSV-2 suppression using a relatively inexpensive drug such as acyclovir might provide an additional means to decrease the spread of HIV (especially in resource-limited settings). Despite strong epidemiologic data linking HSV-2 to HIV acquisition, the reason for the failure of acyclovir to protect against HIV acquisition is still unclear. There is an ongoing study to evaluate the efficacy of acyclovir therapy in preventing HIV transmission from HSV-2/HIV co-infected patients to their uninfected partners.

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