Journal Club


April 3, 2019

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Journal ClubJournal 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.

Editor’s note: The email version of the March 20 edition of IDSA News included incorrect titles for the study reviews that appeared in that issue. The March 20 Journal Club installment, with reviews of studies addressing oral step-down therapy for Enterobacteriaceae bacteremia and oral antibiotics for bone and joint infections, is available here.

For a review of other recent research in the infectious diseases literature, see “In the Literature,”  by Stanley Deresinski, MD, FIDSA, in each issue of Clinical Infectious Diseases.

Erica Kaufman West

Save the Catheter: Antibiotic Locks Are a Viable Option for HSCT Patients

Reviewed by Erica Kaufman West, MD

Central venous catheters (CVCs) are ubiquitous throughout medicine and perhaps no more important than in the hematopoietic stem cell transplant (HSCT) patient. Guidelines for both the prevention and treatment of catheter-related blood stream infection (CRBSI) provide evidence for the important role these infections play in our patients. In the latter guidelines, antibiotic lock therapy (ALT) is listed as a treatment option for uncomplicated CRBSI unless the offending organism is Staphylococcus aureus or Candida species. HSCT patients, however, are a special type of patient for whom physicians may feel that these guidelines are not generalizable.

A retrospective study from Zanwar et al published in Transplant Infectious Disease looked at HSCT patients with tunneled CVCs (not antibiotic impregnated). They separated patients based on catheter colonization (positive cultures in an asymptomatic patient) vs a true CRBSI (symptomatic patient). Of 224 patients and 4,813 catheter-days, colonization was noted in 22 of 294 patients (9.8 percent) and CRBSI in 24 of 224 patients (10.7 percent). Most patients developed positive cultures in the first 3 weeks after CVC insertion. Nearly half of the colonization cultures showed either coagulase negative Staphylococcus or a Gram-negative bacillus (GNB).

Among the patients with colonization, 21 of the 22 had ALT, and clearing of the colonization was possible in 20 of these patients; one progressed to CRBSI. Of those with CRBSI, 20 of the 24 patients had a GNB, one had vancomycin-resistant Enterococcus, one had Candida parapsilosis, one had Moraxella species, and one had Streptococcus species. Fifteen of the 24 had ALT used, and salvage was possible in 13 of 15. All of the nine patients who did not get a lock therapy had GNBs, with six having extended spectrum β-lactamase–producing organisms. There was no mortality due to septicemia in either CRBSI group. Interestingly, none of the patients who had colonization or infection of the catheter had Staphylococcus aureus; GNBs were by far the most common organisms, perhaps related to gastrointestinal tract mucosa injury associated with the transplant conditioning regimens. 

While this study may not be generalizable to other conditions due to the homogeneity of the pathogens isolated, HSCT patients seem to have good outcomes with ALT.

(Zanwar et al. Transplant Infect Dis. 2019;21(1):e13017.)

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Christopher J. Graber, MD, MPH, FIDSAWeight Gain with Antiretroviral Therapy: Examining the NRTI Backbone

Reviewed by Christopher J. Graber, MD, MPH, FIDSA

As antiretroviral therapy for HIV has become increasingly more convenient, well-tolerated, and effective, more attention has centered around metabolic consequences of HIV infection and its treatment. An area of intense debate (initially spurred by articles highlighted in the December 2017 IDSA Journal Club) centers around an observed association between integrase strand transfer inhibitor (INSTI) use and weight gain.

A study recently published in Infection adds a new dimension to this debate by suggesting that changing the nucleoside reverse transcriptase inhibitor (NRTI) backbone (specifically, switching from tenofovir disoproxil fumarate [TDF] to tenofovir alafenamide [TAF]), may also be associated with weight gain. At a single infectious diseases clinic at an academic center in Germany, the authors followed 129 largely virologically suppressed patients who switched from TDF- to TAF-containing regimens from July 2015 to June 2017 and compared their weight gain over time to 112 patients who remained on TDF-containing regimens. Those that switched to TAF were more likely to be male, were taller, had a shorter duration of HIV infection, and were twice as likely to be on an INSTI-containing regimen at baseline (48 versus 24 percent). Approximately 20 patients in the TAF switch group also switched to an INSTI. At 360 days post-switch, TAF switch patients had a mean increase in weight of 3.17 percent versus 0.55 percent in those remaining on TDF. A sensitivity analysis that only included patients who did not switch their third agent showed comparable findings.

While this analysis is limited in that it was single center, retrospective, and the potential contribution of INSTIs to weight gain was not fully controlled for, it nonetheless suggests that assessing the contribution of the NRTI backbone (and TAF in particular) to weight gain may be important. However, the causal mechanism of how a particular NRTI or INSTI would cause weight gain remains a mystery. It is especially unclear how much of the weight gains observed represent true toxicity as opposed to efficacy in removing the catabolic effects of chronic HIV infection such that a Western diet and sedentary lifestyle can have greater effect.  

(Gomez et al. Infection. 2019;47(1):95-102.)