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June 2010
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IDSA Journal Club

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.

Recent Studies Support Safety and Efficacy of Childhood Vaccines
Reviewed by Jason Weinberg, MD

Children who received all recommended vaccines during the first year of life are not at risk for long-term detrimental effects on neurodevelopmental outcome, according to a study published in the June 2010 issue of Pediatrics

This study analyzed publicly available data from a cohort of 1,047 children who underwent neuropsychological testing at 7 to 10 years of age.  Results for children with timely vaccination (vaccine doses received within 30 days of the recommended age; 47 percent of the study population) were compared to results for children with delayed (23 percent), incomplete (20 percent), or absent (0.83 percent) vaccination.  Children with timely vaccination performed no worse on neuropsychological tests than those with untimely vaccination.  Timely vaccination was actually associated with better performance on two measures in a multivariable analysis.  This difference was no longer significant when secondary analyses were conducted, but children with the most timely vaccination again performed no worse than children with the least timely vaccination.

Childhood vaccination remains a public health mainstay, but parental concerns regarding vaccine safety persist.  These concerns can lead to delayed, incomplete, or absent vaccination, increasing the risk of infection for children and their contacts who would otherwise be protected by herd immunity.  Although children included in this study were born between 1993 and 1997, and therefore received fewer vaccines than children undergoing primary vaccination now, the results of this study provide reassurance that timely vaccination is unlikely to be associated with neurodevelopmental problems.

One newer vaccine, which was recently incorporated into the recommended childhood immunization schedule, has decreased hospitalizations for acute gastroenteritis, according to a study in the June 1 issue of The Journal of Infectious Diseases.

Investigators analyzed hospitalization data from 18 states after the pentavalent rotavirus vaccine (RV5) was licensed (2007 and 2008) and compared them to pre-RV5 licensure (2000-2006) data.  The acute gastroenteritis hospitalization rate was 16 percent lower in 2007 and 45 percent lower in 2008 than the pre-licensure median rate.  This effect was greatest in age groups eligible for vaccination but was also present in children either too young or too old to be vaccinated. The investigators estimated that 55,000 acute gastroenteritis hospitalizations were prevented during the 2008 rotavirus season in the United States.

While acute gastroenteritis hospitalization was used as a surrogate for rotavirus-specific hospitalizations, and vaccine coverage data was not available for this study, these encouraging results further support the effectiveness of RV5 in reducing rotavirus-associated disease.  Together, both of these studies reinforce the safety and effectiveness of childhood vaccines.

(Smith and Woods. Pediatrics. 2010; 125(6):1134-1141. and Curns et al. J Infect Dis. 2010; 201(11):1617-1624.)

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Antiretroviral Therapy Dramatically Decreases Rates of HIV Transmission
Reviewed by Jonathan Li, MD

Plasma HIV viral load is known to be one of the most important factors in determining the risk of HIV transmission to an un-infected partner.  In a study published in the June 12 issue of The Lancet, antiretroviral treatment (ART) of the HIV-infected individual resulted in a 92 percent reduction in the rates of HIV transmission to the HIV un-infected partner. 

Investigators performed a secondary analysis of 3,381 HIV-discordant couples enrolled in the Partners in Prevention HSV/HIV Transmission Study, a randomized trial testing the efficacy of acyclovir suppression in preventing HIV transmission.  Participants began ART based on national guidelines, which recommended treatment at CD4 cell counts less than 200-250 cells/μl.  HIV sequencing was performed to establish that the transmission was genetically linked between the partners.

Among the 349 (10 percent) HIV-infected participants who initiated ART, only one genetically linked transmission event was recorded.  In contrast, 102 genetically linked HIV-transmission events occurred from individuals not on ART.  This corresponded to a transmission rate of 0.37 per 100 person-years in those on ART versus 2.24 per 100 person-years in participants not on treatment, a 92 percent reduction in rates of transmission.  Not surprisingly, CD4 cell counts less than 200 cells/μl and higher plasma HIV viral load (>50,000 copies/mL in those with CD4 cell counts >200 cells/μl) were also associated with higher rates of HIV transmission.  

These results are in accordance with another large study of discordant couples and demonstrate the importance of antiretroviral treatment as an HIV prevention strategy.  Despite the dramatic effects noted here, the lone case of HIV transmission by an individual on treatment is a warning that ART use may not be 100 percent effective and should continue to be combined with safe sexual practices.

(Donnell et al. Lancet. 375(9731):2092–2098.)

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Enhancing the Sensitivity of Detecting Catheter-Related Bloodstream Infections
Reviewed by Khalil Ghanem, MD, PhD

All lumens should be cultured to enhance the sensitivity of diagnosing a catheter-related bloodstream infection (CRBSI). The finding comes from a retrospective study published in the June 15 issue of Clinical Infectious Diseases.

Patients had blood cultures drawn from all non-clotted catheter lumens in addition to peripheral vein cultures. CRBSI was defined based on differential time to positivity or differential colony count compared to cultures obtained from a peripheral vein. The investigators used basic probability calculations to determine what fraction of CRBSI would have been missed if one or more lumens had not been cultured.

One hundred and fifty four patients contributed 171 episodes of microbiologically proven CRBSI. The majority of patients studied were immunocompromised. Most infections consisted of coagulase-negative staphylococci, gram-negative rods, and yeast.  If only a single lumen were cultured from a double or triple lumen catheter, 27.2 percent and 37.3 percent of CRBSI, respectively, would have been missed.

The study has several limitations: It was retrospective with a relatively small sample size; information on types of blood culture bottles used, and volume of blood inoculated into each bottle were not provided.  Clinicians should be aware that obtaining samples from all catheter lumens is not recommended unless concomitant peripheral vein cultures are obtained to decrease the likelihood of false-positive culture results.  Additionally, culturing blood from more than one lumen is time consuming, expensive, and may contribute to anemia in critically ill patients.

(Thanks to Karen Carroll, MD, FIDSA, for her insights on this study.)

(Guembe et al. Clin Infect Dis. 2010;50:1575–1579.)

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Antibiotic Therapy and Treatment Failure in Patients Hospitalized for Acute Exacerbations of COPD
Reviewed by Sara Cosgrove, MD

Antibiotics received within two days of hospital admission for acute exacerbations of chronic obstructive pulmonary disease improve treatment success, according to a study in the May 26 issue of the Journal of the American Medical Association.

The retrospective cohort study, using administrative data, included patients with acute exacerbations of COPD at 413 acute care hospitals. Antibiotic treatment was defined as receipt of at least two consecutive doses of first-through-third generation cephalosporins, quinolones, macrolides, tetracyclines, TMP/SMX, amoxicillin, or amoxicillin/clavulanate started on the first or second day in the hospital.  The primary outcome was treatment failure, defined as starting mechanical ventilation after day two of hospitalization, in-hospital mortality, or readmission for COPD within 30 days.

Of 84,621 patients, 79 percent received antibiotics (60 percent of these were quinolones). These patients had lower rates of treatment failure (9.8 percent vs. 11.7 percent), were less likely to require mechanical ventilation (1.1 percent vs. 1.8 percent), had lower in-hospital mortality rates (1 percent vs. 1.6 percent), and had lower rates of readmission (7.9 percent vs. 8.8 percent). After multivariable analyses, receipt of antibiotics remained protective against treatment failure (OR 0.87, 95 percent CI 0.82-0.92).  Patients who received antibiotics were significantly more likely to develop C. difficile diarrhea (0.2 percent vs. 0.09 percent).

While this study supports guidelines recommending treatment with antibiotics, there are some caveats. The retrospective study design leaves open the possibility of confounding factors such as differences in socioeconomic status or management that contribute to the apparent association between antibiotics and improved outcomes.  In addition, data were obtained from administrative databases using ICD-9 codes and were not validated with chart review. The increased rates of C. difficile diarrhea among patients who received an antibiotic also reminds us of the potential consequences of antibiotic use. The relatively high rates of quinolone use may have contributed to this finding. Additional studies are needed to better define which patients benefit from antibiotics, the narrowest spectrum antibiotic that is effective, and the appropriate duration of antibiotic therapy.

(Rothberg et al. JAMA. 2010;303(20):2035-2042.)

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Geoclimatic Influences on Invasive Aspergillosis after Hematopoietic Stem Cell Transplantation (HSCT)
Reviewed by George R. Thompson III, MD

The source and mode of acquisition of Aspergillus spp. is not completely understood.  Infection late after hematopoietic stem cell transplantation (HSCT) has been documented recently, suggesting factors outside of the hospital environment likely play a key role.  Changes in weather conditions are well known to affect spore counts; however, an association with invasive aspergillosis (IA) in allogeneic HSCT patients has not previously been reported.

In the June 15 issue of Clinical Infectious Diseases, investigators describe the results of a comparative analysis of HSCT patients from geographically and diverse regions (Seattle and Houston) to examine potential seasonal variations in IA rates and the possible association of infection with local spore counts and climate.

Data from Seattle demonstrated a high incidence of IA (5.8 percent) after seasonal periods of low precipitation and high temperatures, coinciding with high environmental spore counts.  A comparably lower incidence of IA during the non-summer months (3.3 percent) was also observed at this location, coinciding with low environment spore counts and higher precipitation. 

The Houston cohort was chosen specifically as a comparator to the Seattle group, given the much warmer weather during the spring and summer than in Seattle, and precipitation increases in warmer months rather than decreases.  However, the incidence of IA in Houston HSCT patients was relatively constant throughout the year (1.6-2.4 percent) as were spore counts.  No climatic association on person-month IA rates was seen in this group. 

These findings support the notion that a substantial portion of IA is acquired outside the hospital and that climatic variables affecting spore counts may correlate to IA rates in HSCT patients.  Host and environmental prevention strategies will need to be examined in future studies to decrease the disease burden in this highly susceptible population. 

(Panackal et al.  Clin Infect Dis. 2010;50(12):1588-1597.)

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Long-term Daptomycin Use and the Risk of CPK Elevation
Reviewed by Kathryn E. Stephenson, MD, MPH

Daptomycin is used as an alternative agent to vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) and bacteremia. One of the concerns with long-term use of daptomycin is the development of adverse musculoskeletal events, which are generally heralded by a rise in creatine phosphokinase (CPK) levels.  A study in the June 15 issue of Clinical Infectious Diseases sheds some light on this relationship and the clinical implications.

The investigators studied 108 patients who had received daptomycin 6 mg/kg IV daily for a minimum of 10 days for the treatment of MRSA IE or bacteremia.  Only a small percentage (5.6 percent) of patients had CPK elevations as defined in the study, and only two patients had clinically significant symptoms. CPK elevations were significantly associated with a trough daptomycin level >24.3 mg/L, and five of the six CPK elevations occurred during the first two weeks of therapy.   In addition, CPK elevations were significantly associated with a total body weight >111 kg. 

The authors suggest that CPK levels should be checked more frequently than once weekly during the first two weeks of therapy, but that routine monitoring of daptomycin trough levels is not warranted.  Instead, they propose checking a trough level only for patients with CPK elevations for whom continuing daptomycin therapy would be imperative (as a trough <24.3 mg/L suggests that the elevation is not due to daptomycin). Currently, this may be difficult in clinical practice as daptomycin levels are not available routinely.  The authors also question whether daptomycin dosing should be based on lean body weight to reduce the risk of CPK elevations in obese patients, but warn that doing so might also reduce the efficacy of therapy.

(Bhavnani et al. Clin Infect Dis. 2010;50:1568–1574.)

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:

July 15

  • Clinical Therapeutic Implications of Macrolide Resistance in Mycoplasma pneumoniae
  • Pseudoleukocytosis
  • Treatment of Pneumocystis jirovecii Pneumonia (PCP) When Trimethoprim‐Sulfamethoxazole (TMP‐SMZ) Fails or Cannot Be Used

July 1

  • Treatment of Pulmonary Infection Due to Mycobacterium abscessus
  • Cheeky Mycobacteria
  • Acute Appendicitis: Management with Antibiotic Therapy Alone?

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