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April 2014
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Journal Club

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

Click here for the previous edition of Journal Club. 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.

Haemophilus influenzae Infection During Pregnancy and Adverse Fetal Outcomes
Reviewed by Rachel Simmons, MD

Researchers used public health surveillance in England and Wales to investigate cases of invasive Haemophilus influenzae and pregnancy outcomes, in an article published in the March 19 issue of The Journal of the American Medical Association.

Clinicians were surveyed three months after laboratory-confirmed cases in women aged 15 to 44. Between 2009 and 2012, 171 cases of invasive infection with serotyped isolates were identified. Of these, 144 cases were from unencapsulated H. influenzae. Thirty-eight percent of the women had an underlying condition. The most common presentations were bacteremia followed by pneumonia.

In this study, 75 women were pregnant at the time of infection and 72 had unencapsulated H. influenzae. Pregnant women were more likely to be younger and healthier; all of the pregnant women survived. The overall incidence of infection was higher in pregnant women (3.01 per 100,000 woman-years, compared to 0.22 in non-pregnant women). In infections with unencapsulated H. influenzae that occurred up to week 24 of pregnancy, 44 of 47 cases ended in miscarriage, and three infants were born prematurely. In the 28 infections that occurred after week 24, two infants were stillborn, and eight were born prematurely. Eighty percent of the infants had respiratory distress and/or sepsis at birth. The case fatality rate for neonates and infants was 62 percent. Of all live born infants, one died.

This study demonstrates that invasive H. influenzae infection is uncommon, but the incidence of infection, especially with unencapsulated H. influenzae, which is not prevented by the current vaccine, is increased in pregnancy and associated with a high rate of pregnancy loss. H. influenzae is known to colonize the genital tract and may be an under-recognized cause of pregnancy loss especially in early pregnancy. It is a fastidious organism, so specific culture techniques are needed to confirm the infection. This study also highlights the role of a robust public health surveillance system in identifying rare but potentially preventable or treatable causes of pregnancy loss and neonatal illness.

(Collins et al. JAMA. 2014;311(11):1125-1132.)

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Hospital Readmissions for OPAT: Can We Predict Who Will Be Readmitted?
Reviewed by Jennifer Brown, MD

Outpatient parenteral antibiotic therapy (OPAT) is an effective, cost-saving, and convenient way for patients to receive intravenous antibiotics at home. However, OPAT can be associated with complications such as adverse drug effects, line infections, and hospital readmissions. With OPAT use on the rise, there is a growing need to determine which patients are at risk for complications.

In the March 15, 2014, issue of Clinical Infectious Diseases, researchers described the results of their retrospective review of 782 adult patients who received OPAT between 2009 and 2011. They sought to identify factors that predicted hospital readmission following discharge with OPAT.

Of the 782 subjects, 207 (26 percent) met the primary outcome measure of an unplanned hospital readmission within 30 days of being discharged with OPAT. The main indications for readmission were non-infection related (30 percent), worsening infection (29 percent), new infection (19 percent), and adverse drug reaction (14 percent). In the final regression analysis, age (odds ratio [OR], 1.09 per decade; 95 percent confidence interval [CI], .99-1.21), aminoglycoside use (OR, 2.33; 95 percent CI, 1.17-4.57), a history of previously isolated drug-resistant organisms (OR, 1.57; 95 percent CI, 1.03-2.36), and the number of prior hospital discharges without intravenous antibiotics in the preceding year (OR, 1.20 per prior admission; 95 percent CI, 1.09-1.32) were found to be associated with a higher rate of readmission.

Within the overall cohort, 25 percent (199/782) were treated with cephalosporins and 19 percent (149/782) with carbapenems. Only 5 percent (41/782) received daptomycin and none received intravenous vancomycin.* Thus, the study results may not represent practices in which daptomycin or intravenous vancomycin OPAT use is more common. Other limitations of the study include its retrospective and single-academic center design. Nonetheless, these findings may help clinicians identify OPAT patients with a higher risk for hospital readmission.

*Clarification (5/12/14): Some patients in the study did receive vancomycin (290/782), according to a recently published erratum for the CID article. This use was not significantly associated with readmissions.

(Allison et al. Clin Infect Dis. 2014;58(6):812-9.)

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Is HPV More Commonly Transmitted from Women to Men? Implications for Prevention
Reviewed by Michael T. Melia, MD

While risk factors for human papillomavirus (HPV) transmission have been studied, differences in rates of transmission from women to men versus men to women have not been well-characterized. To help fill this knowledge gap, investigators studied a subset of participants from the prospective HPV in Men (HIM) study. Their findings appear in the April 1 issue of The Journal of Infectious Diseases.

Male study participants from the Tampa, Fla., area with steady female partners were recruited, and 99 couples were analyzed. HPV infection was diagnosed by PCR testing of genital swabs plus swabs of warts or lesions. Results of serologic testing were not reported. Self-reported monogamy was not required.

Of the 99 couples, 65 were HPV-discordant at baseline, such that one partner was infected with at least one HPV genotype not found on his or her partner. Among such couples, incident rates of infection with one of these discordant HPV genotypes were insignificantly higher among men (12.3 infections per 1,000 person-months) than women (7.3 infections per 1,000 person-months). When all 99 couples were studied, incident rates of genital infection were essentially equivalent among men and women (23.9 vs. 22.9 infections per 1,000 person-months, respectively). Couples of ≤2 years’ duration were more likely to acquire infection with any HPV genotype than were couples of >2 years’ duration, with men more likely than women to be infected regardless of relationship duration.

Like several smaller, earlier studies, this study shows that HPV might be more commonly transmitted from women to men than men to women. These findings highlight the importance of HPV vaccination for boys and girls aged 11-12 years, as per the Advisory Committee on Immunization Practices’ current Recommended Immunization Schedules. Catch-up vaccination is recommended for women through age 26 and men through age 21 (with consideration of vaccinating men through age 26).

(Nyitray et al. J Infect Dis 2014;209:1007-15.)

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Stem Cell Transplants and RSV: Factors Behind Progression to Lower Respiratory Tract Infection
Reviewed by Paul Pottinger, MD

Respiratory syncytial virus (RSV) presents major challenges for patients undergoing hematopoietic stem cell transplantation (HSCT): RSV infection of the upper airway causes sniffles and congestion, but it may descend to cause lower respiratory tract infection (LRTI), which is profoundly dangerous and difficult to treat. Fundamental questions remain unanswered about this common infection, including: What host and viral factors are associated with progression to lower-tract infection?

An article in the April 15 edition of The Journal of Infectious Diseases provides some important answers. The investigators retrospectively reviewed the medical records of 181 HSCT recipients with proven RSV upper respiratory tract infection (URI). In their multivariable analysis, several factors predicted progression from URI to LRTI:

  • history of smoking
  • conditioning with total body irradiation
  • absolute lymphocyte count under 100 cells per cubic mm (In fact, the risk of LRTI increased incrementally as the lymphocyte count fell, and none of the patients with a normal lymphocyte count at infection onset progressed to LRTI.)

On the other hand, progression was not different between the following groups:

  • autologous vs. allogeneic donors (This is surprising given the conventional wisdom that “autos” are less likely to develop pneumonia than “allos”.)
  • older vs. younger patients
  • use of high-dose corticosteroids vs. lower dose regimens
  • high levels of RSV-specific serum antibodies vs. lower levels
  • any RSV viral subtype vs. another subtype

Significant questions remain regarding RSV in this vulnerable patient population: Is inhaled or systemic ribavirin best for treatment of active disease, and is immune globulin (polyclonal or monoclonal) effective enough to use in spite of its cost and toxicity? Until an effective RSV vaccine is at hand, these questions will be important to answer. In the meantime, based on this study, we at least have more data on which to base a prognosis for those with RSV URI.

(Kim et al. J Infect Dis. 2014;209(8):1195-1204.)

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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:

April 1

  • Resistance of Plasmodium falciparum to Artemisinin
  • A Fiery Death for Most CD4 Cells in HIV Infection

April 15

  • Cycloserine for Urinary Tract Infection?
  • Malaria or Acute HIV-1 Infection in Kenya: It's 50/50.
  • Getting Closer to Understanding HIV-1 Persistence


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