49th Annual Meeting of the Infectious Diseases Society of America (IDSA)

October 20-23, 2011; Boston, MA
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Oral Bacteria May Predict Risk of Healthcare-Associated Pneumonia

Someday, genetic sequencing of the bacteria in patients’ mouths could be used to assess their risk of acquiring pneumonia during hospitalization and point the way to preventive measures. Speaking at a press conference at the 49th Annual Meeting of the IDSA, Samit Joshi, DO, MD, clinical fellow, Yale University School of Medicine, New Haven, CT, said he and his colleagues identified significant differences in the types and concentrations of oral microbiota between study participants who later developed pneumonia and those who did not. The investigators were specifically concerned with healthcare-associated pneumonia (HCAP), a distinct syndrome from community-acquired pneumonia that is becoming increasingly prevalent. According to the IDSA, HCAP is a serious threat to nursing home residents and community-dwelling older adults who require hospitalization, home infusion, or dialysis.

Based on earlier studies establishing a relationship between poor oral hygiene and increased risk of HCAP, Joshi and associates wondered whether an individual’s oral microbial profile might have predictive value for HCAP. Using 16S rRNA gene pyrosequencing, they analyzed saliva from the mouths of 37 adults, a relatively small cohort that consisted of healthy community-dwelling adults considered at low risk of HCAP (n=19) and individuals thought to have an elevated risk of HCAP, such as nursing home residents (n=10) and mechanically ventilated patients in intensive care (n=8). With an average age of 86 years, the nursing home group trended much older than the groups of community-dwelling adults and intensive care unit (ICU) patients, whose members had an average age of 60 years and 51 years, respectively. All participants were followed for 1 month to document HCAP incidence.

Pyrosequencing assays showed that bacteria from the Streptococcaceae family were the most prevalent across all settings, but concentrations differed between groups. Community dwellers had the highest proportion of Streptococcaceae, followed by nursing home residents and mechanically ventilated ICU patients (65% vs 43% vs 33%, respectively). Joshi said the difference in Streptococcaceae levels between community dwellers and ICU patients was statistically significant (P=.02).

A subanalysis that compared the oral microbial profiles of ICU patients who developed HCAP against those who did not suggested that oral bacterial levels change markedly before the onset of HCAP. At baseline, the average Streptococcaceae level was significantly lower for the subgroup of ICU patients who subsequently developed HCAP compared with the subgroup of ICU patients who remained pneumonia-free (7% vs 49%, respectively; P=.02). Conversely, the oral profiles of ICU patients who developed HCAP contained far greater proportions of Enterococcaceae, Micrococcaceae, and Mycoplasmataceae. The researchers also assessed how closely related the bacterial communities belonging to each family were to one another and observed significantly less divergence between bacterial colonies from the same family among ICU patients who did not contract HCAP than among those who did (24% vs 36%; P=.005).

“By discovering how microbial communities change prior to the development of pneumonia, physicians and scientists could develop new techniques to identify patients at risk for pneumonia and discover new ways to prevent pneumonia in the future,” predicted Joshi. He added that the findings appear to suggest the importance of maintaining the normal composition of oral microbiota in patients at increased risk of HCAP, but that more studies are needed before the results are applied in practice.—Christin Melton

Survey Suggests Patients Hurt by Antimicrobial Shortages

Drug shortages are an ongoing concern in the United States, with the number of drugs unavailable or in short supply almost tripling since 2005. A study presented at the 49th Annual Meeting of the IDSA shows that many physicians have trouble obtaining specific antimicrobial agents for their patients and that the lack of safe alternatives has placed patients’ lives at risk.

Susan Beekmann, RN, MPH, Carver College of Medicine, University of Iowa, and colleagues surveyed physicians affiliated with the IDSA’s Emerging Infections Network about challenges in obtaining desired antimicrobial agents during the past 2 years and asked whether drug shortages had compromised their patients’ well-being. Approximately 500 physicians completed the Web-based questionnaire between May and June 2011, with 78% indicating that the unavailability of a preferred antimicrobial drug had forced them to substitute another agent to treat a patient’s infection. Trimethoprim-sulfamethoxazole (TMP/SMX) injection, amikacin, aztreonam, and foscarnet were the anti-infectives most commonly identified as scarce or unavailable (Figure). In an interview with Clinical Geriatrics^®, Beekmann said other drug shortages mentioned include human immune globulin, penicillin G, cefotetan injection, posaconazole, acyclovir tablets and capsules, yellow fever vaccine, and erythromycin lactobionate injection. 

More than half the respondents (55%) said an inability to obtain a preferred antimicrobial drug had led to worse outcomes, with 64% of patients receiving a more toxic substitute. Other patients were given a more expensive (43%) substitute or a more broad-spectrum antimicrobial agent (40%) than their infection required. Overall, respondents said 30% of patients adversely affected by a shortage required longer hospitalization and 30% suffered long-term morbidity due to “inadequate treatment of infection.” Five physicians said their inability to obtain a preferred antimicrobial likely contributed to a patient’s death. Of those patients adversely affected by a drug shortage, 64% were unable to receive TMP/SMX, 56% could not get amikacin, and 13% did not get foscarnet.

Beekmann said the ongoing antimicrobial shortages endanger patients and society. “Risks to patients include use of a second-line agent…which may result in slower response to therapy, perhaps a longer hospitalization, and, in some cases, drug failure,” she explained. “The primary risks to society revolve around the issue of increasing antimicrobial resistance. If a narrower-spectrum agent isn’t available—for example, amikacin—a broader spectrum agent may be used instead, [like] a newer generation cephalosporin or a carbapenem, which increases the likelihood of developing antimicrobial resistance over the long term.” Cost is another concern. “Most of the agents in shortage are generics and are cheaper; second-line agents that are used instead are often still under patent and cost more—sometimes a lot more,” she noted.

US law does not require drug manufacturers to report shortages or discontinuations, and 70% of respondents only learned that the requested antimicrobial was unavailable when the pharmacy notified them. A minority of physicians surveyed (26%) learned about shortages from an official source, such as the US Food and Drug Administration (FDA) Website (http://1.usa.gov/FDADrugShortages). The American Society of Health-System Pharmacists (ASHP) also tracks anticipated, current, and resolved drug shortages at www.ashp.org/DrugShortages and proposes substitutions for drugs that are unavailable.

Professional medical societies are pressing for legislation that would require manufacturers to report shortages and their causes to the FDA. “Congress has addressed this issue via GAO [Government Accountability Office],” said Beekmann. She recommended reading the GAO’s report (www.gao.gov/products/GAO-12-315T) and the article “Forgotten Antibiotics: an Inventory in Europe, the United States, Canada, and Australia,” which appears in the January 2012 issue of Clinical Infectious Diseases. “This article assesses the availability of potentially useful older antibiotics, and is another tactic to address antimicrobial shortages and increasing antimicrobial resistance,” she said.—Christin Melton