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January 2015
IDSA 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.

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.

Prior Urine Cultures: Does the Past Predict the Present?
Reviewed by Christopher J. Graber, MD, MPH, FIDSA

When prescribing therapy for urinary tract infections prior to urine culture results becoming available, clinicians often look to prior urine cultures to get an idea of whether or not the current infecting organism will be susceptible to a particular antibiotic, despite limited data to support this approach.

In a recent article in Clinical Infectious Diseases, authors from two health care systems in Toronto and Chicago examined 22,019 consecutive pairs of positive urine cultures from 4,351 patients. Patients had a mean age of 72 years with a 184-day mean interval between cultures; 78 percent of the paired cultures were from females. The organism was the same in 9,590 pairs (44 percent); these were included in an analysis of antimicrobial susceptibility.

Organism correspondence was approximately 80 percent within 1 week between cultures, declining to 57 percent at 4-8 weeks and still remaining at 49 percent at >32 weeks. Among the paired isolates growing the same organism, the susceptibility profile was the same or better in 83 percent at 4-8 weeks and 75 percent at >32 weeks, rising to 87 percent and 80 percent, respectively, if no antibiotics were prescribed in the interim, and falling to 80 percent and 73 percent, respectively, if E. coli was the infecting organism. In a subset of paired cultures for which ciprofloxacin susceptibility and utilization data were available and the initial isolate was ciprofloxacin-susceptible, the likelihood of ciprofloxacin susceptibility in the subsequent isolate remained above 80 percent if no fluoroquinolones had been prescribed in the interim, regardless of time interval. If fluoroquinolones had been prescribed in the interim, ciprofloxacin susceptibility fell to approximately 50 percent at 1-2 weeks but increased to 60-75 percent with longer timeframes between cultures.

While these data should be carefully interpreted, they usefully inform empiric prescription of antibiotic therapy for urinary tract infections but still reinforce the need for follow-up on urine culture results to guide definitive therapy.

(MacFadden et al. Clin Infect Dis. 2014;59(9):1265-71.)

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Treating Pyogenic Vertebral Osteomyelitis: 6 Weeks or 12 Weeks of Antibiotics?
Reviewed by Manie Beheshti, MD

Lack of robust evidence to guide the treatment of osteomyelitis poses a common clinical challenge for ID physicians. Duration of therapy is typically backed by observational data and expert opinion. In an article published online in the Lancet on Nov. 5, researchers reported findings of their randomized, controlled trial assessing the non-inferiority of 6 versus 12 weeks of therapy for pyogenic vertebral osteomyelitis.

Conducted across multiple centers in France, the study randomized more than 350 patients to 6 versus 12 weeks of therapy with antimicrobial regimens selected in agreement with French guidelines. Patients across both arms had similarities in (1) anatomical vertebral site of involvement, (2) rates of concomitant infective endocarditis and blood culture positivity, and (3) number of patients with neurological signs.

Clinical cure was equal in both arms (90.9 percent in both the 6- and 12-week groups) exhibiting non-inferiority of the 6-week regimen compared with the 12-week. In their post-hoc analysis, the authors highlighted that, likely due to low sample size, non-inferiority was not met in certain subgroups: age greater than 74, presence of immunosuppression or diabetes, endocarditis, or neurological signs. Conversely, superiority of the 12-week regimen was not demonstrated in any subgroup. While there was no difference in the types of antimicrobials used between groups, most patients received less than 2 weeks of intravenous therapy, and the most common oral regimen included rifampin with a fluoroquinolone.

In an era of increasing need for stewardship to help avoid collateral damage from antimicrobials, this study provides rare data in the realm of osteomyelitis that suggests in the right clinical setting a shorter course of therapy is non-inferior for patients with pyogenic vertebral osteomyelitis.

(Bernard et al. Lancet, early online publication, Nov. 5, 2014.)

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Recurrent SSTIs in Pediatric Patients: Persistent Colonization or Hidden Environmental Reservoirs?
Reviewed by Terri Stillwell, MD

Recurrent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) are common referrals for pediatric ID physicians. It is often thought that these infections are due to persistent colonization versus reinfection with diverse strains. Current recommendations speak to decolonization protocols but are often met with varying success. If recurrent infections are caused by similar strains, then are subsequent infections due to failed decolonization or ongoing exposure from an unseen source? Two recent studies attempt to shed additional light on this topic.

In an article from the September issue of the Journal of the Pediatric Infectious Diseases Society, the authors utilized molecular epidemiology to characterize the strain relatedness of MRSA isolates from recurrent SSTIs in otherwise healthy children. The objective was to determine whether subsequent MRSA SSTIs were reinfections by isolates similar to previous infections or new infections with distinct strains. From January 2005 to January 2011, 105 patients had 248 discrete MRSA infections. Ninety percent of repeat infections were attributable to strain types that were identical to those causing prior infections. Data regarding possible decolonization efforts were not available. The authors suggested that, given this degree of relatedness, decolonization should theoretically impact recurrences, but perhaps current decolonization schemas are too brief to achieve true eradication.

In a second article, from the November JAMA Pediatrics, investigators took a slightly different approach, hypothesizing that perhaps environmental contamination leads to recurrent infections. The authors obtained cultures from 21 household surfaces and pets (dogs and cats) to assess the potential for environmental contamination. Cultures of patients’ nares, axilla, and inguinal folds were also obtained to determine presence of colonization. These samples were then compared with one another and with infection isolates to determine strain relatedness.

From January 2012 to February 2013, 50 children with culture-proven MRSA infections participated; 35 had their MRSA-infection strains available for analysis. Of the 50 participants, 64 percent (32/50) had at least one environmental sample positive for S. aureus, with a median of three positive surfaces overall. Twenty-three percent (6/26) of dogs and 7 percent (1/14) of cats were also found to be positive. Forty-two percent (21/50) of the participants themselves were colonized with S. aureus at the time of the study; 28 percent (14/50) had an environmental sample that matched their colonizing strain. Of those that had their MRSA-infection strains available for study, 31 percent (11/35) had concordance between their infection strain and their colonizing strain, and 37 percent (13/35) had concordance between their infection strain and an environmental strain. Only one pet isolate and infection/colonization isolate pair were concordant.

Given these studies’ findings, attempts to optimize decolonization techniques should continue. However, potential environmental reservoirs for reinfection also deserve consideration, in order to break the chain of transmission, in the hopes of preventing recurrent infections.

(Al-Zubeidi et al. J Ped Infect Dis. 2014;3(3):261-264. and Fritz et al. JAMA Pediatr. 2014;168(11):1030-1038.)

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Making Fecal Microbiota Transplantation for Recurrent C. difficile Easier to Swallow
Reviewed by Nina Kim, MD, MSc

Recurrent Clostridium difficile infection (RCDI) can be a major scourge for patients and clinicians faced with the failure of conventional antibiotic therapy. Fecal microbiota transplantation (FMT) has emerged as a promising strategy to restore the disrupted gut microflora of patients with RCDI. However, widespread use of FMT has been hampered by the lack of controlled studies or standardization, and the practical challenges of balancing thorough donor screening with the need for prompt treatment while dealing with fresh samples of limited viability—not to mention the distasteful nature of the procedure and the risks of nasogastric or endoscopic delivery. A study published in the Nov. 5 issue of the Journal of the American Medical Association offers a noninvasive and feasible alternative to an otherwise cumbersome therapy.

In this open-label, single-arm study, investigators prepared fecal suspensions from carefully pre-screened healthy donors, pipetted samples into acid-resistant capsules, and stored these at -80°C prior to administration. Twenty patients aged 11 to 89 years old who met their criteria for RCDI (three or more episodes of mild to moderate CDI and failure of vancomycin taper, or two or more episodes of severe CDI requiring hospitalization) ingested a total of 30 capsules over 2 consecutive days. In the end, all but two patients (90 percent) achieved clinical resolution of diarrhea in a mean of 4 days without relapse during 8 weeks of follow-up, comparable to response rates of freshly prepared FMT reported in the literature. The capsules were generally well tolerated aside from transient abdominal cramping and bloating observed in six patients. Notably, no patient vomited after capsule administration.

Despite its limitations as a small, short-term, single-center study, this trial has demonstrated that oral administration of frozen fecal microbiota is a safe, feasible, and cost-effective route of delivery that opens the door for potentially greater access and ideally more rigorous study of FMT.

(Youngster et al. JAMA. 2014(17);312:1772-1778.)

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Antibiotics and Hypoglycemia Risk Among Older Patients Taking Sulfonylureas
Reviewed by Michael T. Melia, MD

Sulfonylureas stimulate pancreatic insulin secretion and can cause hypoglycemia, which in turn can be associated with significant morbidity. While concurrent use of certain antibiotics has been shown to increase the risk of hospitalization for hypoglycemia, this association has been incompletely explored.

In a recent issue of JAMA Internal Medicine, investigators used Texas Medicare claims data to analyze this association. They reviewed glyburide or glipizide prescriptions that overlapped by at least one day with those for one of 16 commonly prescribed antibiotics. For persons prescribed one of seven antimicrobials previously associated with hypoglycemia, they collected data on hypoglycemic events resulting in emergency department evaluation or inpatient hospitalization within 14 days of antibiotic use. To calculate the excess cost of these episodes, they averaged the cost of hypoglycemia management among patients prescribed one of five antimicrobials associated with hypoglycemia and subtracted the average post-antibiotic costs of the non-interacting antibiotics.

The investigators analyzed 133,535 episodes of overlapping prescriptions; rates of hypoglycemia ranged from 0.17 percent to 1.87 percent. When compared with antimicrobials not associated with hypoglycemia, clarithromycin, levofloxacin, trimethoprim-sulfamethoxazole, metronidazole, and ciprofloxacin each significantly increased the risk of hypoglycemia; the number of prescriptions needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. Each prescription for one of these five agents was associated with an increased Medicare cost of $30.54.

While studies based upon claims data have inherent limitations, the investigators controlled for a number of variables, including age, sex, race/ethnicity, Medicaid eligibility, comorbidities, prior hospitalizations for hypoglycemia, and nursing facility residence. Their results were unchanged when stratifying data by the antibiotic indication, as well as when patients with renal disease or receiving insulin were excluded. Their study makes an important contribution to our knowledge about clinically important drug-antibiotic interactions among older patients, and it highlights the hidden costs—both financial and medical—associated with antibiotic prescriptions.

 (Parekh et al. JAMA Intern Med. 2014;174(10):1605-1612.)

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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:

January 15

  • Seals as the Original Source of Tuberculosis in the Americas
  • Staphylococcal Small-Colony Variants and Prosthetic Joint Infections
  • Case Vignette: White Urine—Albinuria
  • Case Vignette: Malaria: Monkey to Human

January 1

  • Growing Risk of Viral Hemorrhagic Fever in India: Crimean-Congo Hemorrhagic Fever
  • Growing Risk of Viral Hemorrhagic Fever in India: “Monkey Fever”
  • Case Vignette: Hepatic Echinococcosis and Pulmonary Embolism

December 15

  • After the “Blood Diamond” Conflict: Lassa Fever in Sierra Leone
  • Case Vignettes

December 1

  • Molecular Epidemiology of Ebola Virus in Sierra Leone, 2014
  • Febrile Illness in Sierra Leone: A Predictor of the Ebola Epidemic?
  • Infection Apparently Acquired During Travel

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