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May 1, 2008
IDSA Literature Review - April 2008

In this new 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 more from Clinical Infectious Diseases and The Journal of Infectious Diseases, see the "In the IDSA Journals" section of IDSA News.



High-Dose Vancomycin May Lead to Nephrotoxicity 

Sara E. Cosgrove, MD, MS

High doses of vancomycin may be associated with increased risk of nephrotoxicity, according to a study in the April issue of Antimicrobial Agents and Chemotherapy.  

Lodise et al. compared 26 adults who received  4 grams of vancomycin or more daily to 220 who received less than 4 grams and to 45 who received linezolid.  Vancomycin dose  of 4 grams per day or more was an independent predictor of time to nephrotoxicity. Total body weight of 101.4 kg or more, estimated creatinine clearance of  86.6 mL/min or less, and ICU admission also predicted nephrotoxicity. 

This was a retrospective, non-randomized study in which bias may be introduced by patient factors that lead clinicians to choose higher doses of vancomycin that may also be associated with increased risk of nephrotoxicity. Nevertheless, the results suggest that clinicians should monitor patients carefully when using high doses of vancomycin, particularly patients with risk factors for renal dysfunction or on concomitant nephrotoxic agents. (Lodise et al., Antimicrob Agents Chemother. 2008;52:1330-6.)

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Antibiotics May Prevent Catheter-related Bloodstream Infections—But Use Caution 

Sara E. Cosgrove, MD, MS 

Both topical and intraluminal antibiotics helped prevent catheter-related bloodstream infection (CR-BSI) among hemodialysis patients in a meta-analysis published in the April 15 issue of Annals of Internal Medicine, but it may be too soon to consider changing practice. 

Mupirocin or polysporin triple-antibiotic ointment at the catheter insertion site decreased CR-BSI, Staphylococcus aureus bacteremia, and exit site infections compared to no ointment in three pooled studies.  Use of intraluminal antibiotics (or “antibiotic lock therapy”), in which antibiotic solutions are placed in the lumen of the catheter between dialysis sessions, decreased CR-BSI but not S. aureus bacteremia or exit site infections compared to no antibiotics in 11 pooled studies; gentamicin was the most commonly studied agent. 

However, some additional factors should be considered before changing practice in this area.  First, several of the studies included in the meta-analysis were small and unblinded, and use of meta-analysis cannot compensate for flaws in individual studies.  Second, rates of emergence of resistance—always a serious concern—were not evaluated.  Non-antimicrobial alternatives are available, such as povidone-iodine antiseptic at exit sites, which is recommended in the current IDSA guidelines for prevention of catheter-related infections.  At this point, use of topical and intraluminal antibiotics should likely be reserved for patients with recurrent CR-BSIs who have limited options for vascular access.  (James et al., Ann Intern Med. 2008;148:596-605.)

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Resistant Pneumococci Decline with Reduced Antibiotic Use 

Melinda M. Pettigrew, PhD

Rapid seasonal declines in otitis media caused by antibiotic-resistant Streptococcus pneumoniae occurred concomitant with seasonal reductions in antibiotic prescriptions among Jewish children in southern Israel in a study in the April 15 issue of The Journal of Infectious Diseases. Authors Dagan et al. did not observe the same seasonal decline in resistant strep among Bedouin children in the same region, among whom antibiotic prescription patterns are less seasonal. 

Several studies have linked high levels of antibiotic use with high levels of antibiotic resistance. This study is particularly noteworthy because few have demonstrated that reductions in antibiotic prescriptions rapidly result in lower levels of antibiotic resistance in the community. 

It may be that prescriptions to the Jewish children were reduced to a critical threshold needed to achieve a significant reduction in resistance. Further studies are needed to define this threshold. More research is also needed to evaluate whether these data are generalizable to populations outside of Israel and whether reductions in antibiotic prescriptions will similarly impact resistance in other bacteria species. (Dagan et al., J Infect Dis. 2008;197:1094-1102.)

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Meta-analysis Confirms Need for Droplet Precautions until Influenza Symptoms Resolve 

Khalil G. Ghanem, MD

A new meta-analysis of duration of influenza virus shedding and symptoms confirms conventional wisdom and has implications for infection control. The study of 56 influenza virus challenge studies in 1,280 healthy human volunteers is published in the April 1 issue of the American Journal of Epidemiology.

Overall, virus shedding was detected one day after inoculation and persisted for a total of 4.8 days. Shedding was found to be lower among persons infected with influenza B as compared to influenza A. Approximately 70 percent of volunteers developed symptoms: 58.8 percent developed upper respiratory symptoms, 21 percent developed lower respiratory symptoms, and 34.9 percent developed a fever. Symptoms peaked by day two or three, and returned to baseline by day 10. Viral shedding began approximately 10 to 12 hours before the onset of symptoms and decreased in parallel to the symptom scores. 

This study confirms prior opinion on the duration of viral shedding and the frequency of symptoms in influenza infection. It also highlights the importance of using droplet precautions until symptoms abate in hospitalized patients suspected or diagnosed with influenza infection. 

There are several limitations to note. Viral dynamics may be different in more debilitated hosts. Viruses used in these experiments may have been less pathogenic than wild-type viruses. Also, most of the volunteers had low pre-existing immunity to these viruses. (Carrat et al., Am J Epidemiol. 2008;167:775-85.)

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