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.
For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.
Ivermectin Effective Therapy for Recalcitrant Head Lice
Reviewed by Jason Weinberg, MD
Oral ivermectin is an effective treatment alternative to topical insecticides in patients with difficult-to-treat head lice. The finding comes from a study published in the March 11 issue of The New England Journal of Medicine.
A total of 812 infested patients from 376 households were included in this multicenter, cluster-randomized, double-blinded, placebo-controlled trial. All patients, who were at least 2 years old and weighed at least 15 kg, came from households in which at least one household member had failed a recent course of topical insecticide therapy. On days 1 and 8, patients from randomized households received either oral ivermectin (400 micrograms/kg) plus placebo lotion, or malathion lotion plus placebo tablet.
Oral ivermectin was both noninferior and superior to malathion lotion in achieving the primary outcome, with 95.2 percent of patients receiving ivermectin versus 85.0 percent of patients receiving malathion being free of head lice at day 15. Oral ivermectin was also superior with regard to the secondary outcomes: absence of head lice at early (days 2 and 8) and later (days 22 and 29) times. Adverse events were infrequent and occurred at a similar rate in the two study groups.
More patients preferred oral ivermectin (78.3 percent) than topical malathion (13.0 percent) in this study, suggesting that increased compliance in a non-study setting may further enhance ivermectin’s efficacy. There is some concern that the increased use of ivermectin could lead to the emergence of resistance in head lice. Limiting its use to patients who have failed topical therapy, as the authors of this study advocate, should limit this risk. In general, it is refreshing to see solid evidence for a simple and effective therapy for difficult-to-treat head lice infestations, which remain frustrating for patients and physicians alike.
(Chosidow et al. NEJM 2010; 362:896-905.)
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Some Protease Inhibitors Not Associated with Pre-Term Birth
Reviewed by Khalil Ghanem, MD, PhD
The use of certain protease inhibitors (PIs) to treat HIV-infected pregnant women was not associated with increased risk of pre-term birth, according to a report in the April 1 issue of The Journal of Infectious Diseases. The finding comes from a large prospective cohort study designed to assess the risks of antiretroviral therapy in pregnant women and their infants.
The association between the use of PIs and pre-term birth has been controversial. The issue is critical because the current U.S. guidelines recommend combined antiretroviral therapy (cART) during pregnancy to decrease vertical transmission of HIV. No randomized controlled trials have been conducted; a common limitation of previous observational studies was confounding by indication: the possibility that women who were started on cART were sicker and thus at increased risk of pre-term birth.
In this study, among 777 HIV-infected pregnant women who were not receiving cART at conception and were enrolled in the prospective cohort, 558 received a PI-containing regimen. The most commonly used PIs included nelfinavir and the combination of lopinavir and ritonavir. Using logistic regression models to adjust for potential confounders, PI use was not associated with pre-term birth (OR 1.22, 95 percent CI: 1.70-2.12) compared with regimens that did not include a PI. The major limitations of the study were the relatively small sample size, which may have missed a small but clinically significant increased risk of pre-term birth, and the limited number of PIs that were assessed.
The ideal antiretroviral regimen to use during pregnancy is unknown. This study suggests that some PIs (namely lopinavir/ritonavir) may be safe to use during pregnancy. Clinicians should always refer to the latest guidelines when treating pregnant women as this area is in constant flux.
(Patel et al. J Infect Dis. 2010 201(7):1035-44.)
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An Update on Cephalosporins
Reviewed by Sara Cosgrove, MD
Two recent studies published in Antimicrobial Agents and Chemotherapy provide additional information about two commonly prescribed cephalosporin antibiotics, ceftriaxone and cefepime.
The first study, published in the journal’s April issue, provides additional support for the Food and Drug Administration (FDA)’s 2009 decision to modify a warning from 2007 regarding the potential risk of precipitation and organ damage when ceftriaxone and calcium containing products are co-administered. Investigators searched the FDA Adverse Event Reporting System (AERS) for cases who received ceftriaxone and calcium as well as for controls who received ceftazidime and calcium between 1998 and 2007. Adverse events were classified based on the possibility that they were associated with an embolic event causing pulmonary or renal failure.
Although the 104 patients in the ceftriaxone-calcium group had more probable associated embolic events than the 99 patients in the ceftazidime-calcium group (7.7 percent vs. 4 percent), they had had fewer possible associated embolic events (20.2 percent vs. 30.3 percent). These results suggest that the current FDA recommendation that patients more than 28 days old can receive both agents as long as the infusion line is flushed between administrations is reasonable.
A second study, published in the journal’s March issue, suggests that cefepime doses of 2 grams every 8 hours may optimize outcomes in patients with normal renal function and non-urinary tract Pseudomonas aeruginosa infections. The authors evaluated 56 patients with respiratory (66 percent), skin and skin structure (25 percent), and bloodstream (9 percent) infections in which microbiological success was achieved in 57 percent of patients. As noted in other studies, the percentage of the dosing interval that the free drug concentration remains above the MIC of the infecting organisms (ƒT > MIC) was associated with microbiologic success; the failure rate was 78 percent if the ƒT > MIC was ≤ 60 percent in the entire cohort and 100 percent among patients with respiratory infections or bacteremia.
Using a Monte Carlo simulation, the authors estimated that at the current Clinical and Laboratory Standards Institute (CLSI)-defined breakpoint of 8 µg/ml for P. aeruginosa, a cefepime dose of 2 grams every 8 hours or as a 30-minute or 3-hour infusion has a ≥ 82 percent likelihood of achieving a ƒT > MIC of at least 60 percent in patients with normal renal function. Standard doses of cefepime were much less likely to achieve adequate pharmacodynamic targets. P. aeruginosa isolates with MICs < 8 µg/ml may not require such aggressive dosing; however, most microbiology laboratories do not report the actual MIC of the isolate. Thus, for serious infections caused by P. aeruginosa, clinicians may want to consider using cefepime at a dose of 2 grams every 8 hours.
(Steadman et al. Antimicrob. Agents Chemother. 2010;54(4):1534-1540 and Crandon et al. Antimicrob. Agents Chemother. 2010;54(3): 1111-1116.)
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Invasive Fungal Infections (IFIs) in Solid Organ Transplant Recipients
Reviewed by George R. Thompson III, MD
The Transplant-Associated Infection Surveillance Network (TRANSNET) conducted a prospective evaluation of invasive fungal infections (IFIs) in organ transplant recipients. The results of their observational study, which will likely affect future research and possibly the development of new treatment and prevention strategies, were published in the April 15 issue of Clinical Infectious Diseases.
In prior studies, the incidence and etiology of fungal infections has varied by the type of organ transplant and by the individual transplant center. TRANSNET was established in 2001 to perform prospective surveillance among geographically diverse U.S. organ transplant centers to better define the true burden of IFIs in these patients.
Only proven and probable IFIs were included as cases in this study. There were 1,208 proven (42 percent) and probable (58 percent) IFIs among 1,063 organ transplant recipients during the surveillance period (March 2001 to March 2006). Invasive candidiasis (53 percent), aspergillosis (19 percent), cryptococcosis (8 percent), non-Aspergillus-molds (excluding Zygomycetes) (7 percent), and endemic mycoses (5 percent) were the most common. Proven zygomycosis and Pneumocysts jiroveci infection were uncommon (<3 percent).
The time to diagnosis of infection varied by organism. Early infection (<90 days post transplantation) was predominantly due to Candida and Aspergillus species. However, the majority of all infections occurred >90 days after transplantation with a substantial number occurring more than three years after transplant. These late infections were most commonly due to cryptococcosis, non-Aspergillus molds, and endemic mycoses.
In the incidence cohort, the 12-month cumulative incidence of infection was 3.1 percent. Small bowel transplant recipients were at the highest risk (12 percent), followed by heart-lung (9 percent), liver (5 percent), pancreas and kidney-pancreas (4 percent), heart (3 percent), and kidney (1 percent) recipients.
These findings will undoubtedly have a significant impact on future studies examining organ-specific risk factors for post-transplant IFI and may lead to new strategies for diagnosis, prophylaxis, and/or treatment in this highly vulnerable population.
(Pappas et al. Clin Infect Dis. 2010;50:1101-1111.)
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Improving Infection Control: Bacterial Meningitis and Spinal Procedures
Reviewed by Kathryn E. Stephenson, MD, MPH
Two small clusters of bacterial meningitis among healthy women who received intrapartum spinal anesthesia were reported in the U.S. between September 2008 and May 2009, raising the possibility that infection control measures for spinal procedures may not be widely followed. The report, which first appeared in the Centers for Disease Control and Prevention (CDC)’s Morbidity and Mortality Weekly Report (MMWR) in January, was also published in the March 17 issue of the Journal of the American Medical Association.
In four of the five cases, Streptococcal salivarius, a common organism in the mouth, was found in the women’s blood and/or cerebral spinal fluid. All cases were marked by the rapid onset of symptoms after spinal procedures; one of the women died. Each cluster – one in New York, the other in Ohio – was associated with a single anesthesiologist. CDC investigators concluded that the two clusters of meningitis were most likely due to breaches in aseptic technique allowing droplet transmission of S. salivarius from the oropharynx of the anesthesiologists to the patients. In other words, the doctors did not wear surgical masks.
The Healthcare Infection Control Practices Advisory Committee (HICPAC) recommends that surgical masks be worn by spinal procedure operators to prevent infections, but this recommendation, issued in June 2007, is not yet in widespread practice. It applies to many diagnostic and therapeutic spinal procedures, including lumbar puncture, myelography, and spinal anesthesia, and is particularly important for procedures that involve placing a catheter or injecting material into the spinal canal or epidural space. The authors advise that health care facilities where these procedures are performed should raise awareness of HICPAC recommendations and reinforce adherence to infection-control guidelines among staff.
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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:
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