The impact of anti-infective drug shortages on hospitals in the United States: trends and causes.

Anti-infective shortages pose significant logistical and clinical challenges to hospitals and may be considered a public health emergency. Anti-infectives often represent irreplaceable life-saving treatments. Furthermore, few new agents are available to treat increasingly prevalent multidrug-resistant pathogens. Frequent anti-infective shortages have substantially altered patient care and may lead to inferior patient outcomes. Because many of the shortages stem from problems with manufacturing and distribution, federal legislation has been introduced but not yet enacted to provide oversight for the adequate supply of critical medications. At the local level, hospitals should develop strategies to anticipate the impact and extent of shortages, to identify therapeutic alternatives, and to mitigate potential adverse outcomes. Here we describe the scope of recent anti-infective shortages in the United States and explore the reasons for inadequate drug supply.

Impact of carbapenem resistance and receipt of active antimicrobial therapy on clinical outcomes of Acinetobacter baumannii bloodstream infections.

Nosocomial Acinetobacter baumannii bloodstream infections occur with significant prevalence and mortality. The relationship between carbapenem resistance in A. baumannii and patient outcomes remains unclear. A retrospective cohort study was conducted on patients with A. baumannii bacteremia. Outcomes, controlling for confounders, were compared for carbapenem-nonresistant A. baumannii (CNRAB) and carbapenem-resistant A. baumannii (CRAB). The primary outcome studied was all-cause hospital mortality, and the secondary endpoints evaluated were time to mortality, time to negative cultures, and length of stay postinfection for survivors. A total of 79 patients, 37 infected with CRAB and 42 with CNRAB, were studied. Hospital mortality was greater in the CRAB group as determined based on bivariate analysis (P < 0.01); however, this effect was nullified when controlling for relevant confounders with logistic regression and a Cox proportional-hazards model (P = 0.71 and 0.75, respectively). Values for time to mortality and time to negative cultures did not differ between the groups. The median number of days of stay postinfection for survivors was greater for the CRAB group than the CNRAB group (14 versus 6.5; P < 0.01). Patients who received active antimicrobial therapy were less likely to die (93.5% versus 74.2%; P = 0.02), regardless of carbapenem susceptibility classifications, and this result was robust in the multivariate model (P = 0.02). Trends existed for improved outcomes in patients receiving an active beta-lactam, and patients fared worse if they had received a polymyxin as an active agent. Patients with CRAB bloodstream infections were more chronically ill and had more comorbidities. Inactive therapy was more important than carbapenem susceptibility with respect to outcomes, was a strong predictor of death, and is potentially modifiable.

Pharmacokinetic assessment of peramivir in a hospitalized adult undergoing continuous venovenous hemofiltration.

OBJECTIVE: To report a sieving coefficient for peramivir in a patient receiving continuous venovenous hemofiltration (CVVH). CASE SUMMARY: An 18-year-old male presented with chills, myalgias, and dyspnea and was hospitalized. Nasal secretions were positive for influenza by rapid antigen test at an outside facility and oseltamivir was commenced. Oral absorption was predicted to be unreliable, and intravenous peramivir was accessed as an emergency investigational new drug applicaiton (eIND). CVVH was initiated after the development of acute renal failure, with blood samples collected to determine peramivir concentrations. DISCUSSION: Peramivir, an intravenous investigational neuraminidase inhibitor with activity against influenza viruses, has limited data for dosing in the setting of CVVH. A single patient received 600 mg of peramivir intravenously and had blood and ultrafiltrate concentrations measured serially. A sieving coefficient of approximately 0.9 was identified. CONCLUSIONS: Peramivir is well cleared by CVVH, and drug exposure is potentially predictable based on flow rates. Further study is necessary.

Antimicrobial stewardship programs: methods of operation and suggested outcomes.

The judicious use of antibiotics is an important strategy to preserving efficacy in the treatment of infectious diseases. Infectious disease practitioners are poised to provide patient-specific recommendations for appropriate agents and to optimize dosage and duration of therapy. Antimicrobial stewardship programs (involving pharmacists, physicians and other healthcare providers) are increasing in number as antibiotic resistance increases with a disproportionately small number of new agents being developed. Two strategies for antimicrobial stewardship are currently endorsed by national organizations and include preauthorization/formulary restriction and prospective audit with feedback. As it is important for programs to choose appropriate clinical and financial outcomes goals in order to assure sustainability, we review these strategies and discuss the impact of each on clinical outcomes and costs.

Prospective approach to managing antimicrobial drug shortages.

Antimicrobial drug shortages continue to increase, with few new therapeutic options available. Nationally, proposals have been offered to alleviate drug shortages; however, these recommendations are unlikely to effect change in the near future. Thus, antimicrobial stewardship leaders in acute care hospitals must develop a prospective management strategy to lessen the impact of these shortages on patient care. Herein, we describe several resources available to aid professionals in antimicrobial stewardship and healthcare epidemiology to manage drug shortages. An effective approach should include prospectively tracking shortages and maximizing inventory by appropriately managing usage. Several tenets should underpin this management. Alternative agents should be rationally chosen before the inventory of the primary agent has reached zero, ethical considerations should be taken into account, and timely notification and communication with key stakeholders should occur throughout the prescribing and dispensing process.