Alan E. Gross

Epidemiology and Predictors of Multidrug-Resistant Community-Acquired and Health Care-Associated Pneumonia

ABSTRACT There are limited U.S. data describing the risk factors for multidrug-resistant organism (MDRO) isolation in community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP). However, concern for the presence of these pathogens drives the prescribing of empiric broad-spectrum antibiotics for CAP and HCAP. A retrospective study of all adults hospitalized with community-onset pneumonia (CAP and HCAP) at a large U.S. medical center from January 2010 to December 2011 was conducted. The objective was to ascertain the rate of pneumonia caused by MDROs and to evaluate whether HCAP is a risk factor for MDRO pneumonia. Univariate and propensity score-adjusted multivariate analyses were performed. A total of 521 patients (50.5% CAP and 49.5% HCAP) were included. The most common etiologies of pneumonia were primary viral and Streptococcus pneumoniae. MDROs were isolated in 20 (3.8%) patients overall, and MDROs occurred in 5.9% and 1.9% of HCAP and CAP patients, respectively. The presence of an MDRO was not associated with HCAP classification (odds ratio [OR] = 1.95; 95% confidence interval [95% CI], 0.66 to 5.80; P = 0.23) or with most of its individual components (hemodialysis, home infusion, home wound care, and ≥48-h hospitalization in the last 90 days). Independent predictors of MDRO included the following: Pseudomonas aeruginosa colonization/infection in the previous year (OR = 7.43; 95% CI, 2.24 to 24.61; P < 0.001), antimicrobial use in the previous 90 days (OR = 2.90; 95% CI, 1.13 to 7.45; P = 0.027), admission from a nursing home (OR = 4.19; 95% CI, 1.55 to 11.31; P = 0.005), and duration of hospitalization in the previous 90 or 180 days (P = 0.013 and P = 0.002, respectively). MDROs were uncommon in HCAP and CAP. HCAP did not predict MDRO isolation. Local etiology of community onset pneumonia and specific MDRO risk factors should be integrated into therapeutic decisions to prevent empirical overprescribing of antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa.

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.

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.

Oral Ribavirin for the Treatment of Noninfluenza Respiratory Viral Infections A Systematic Review

Objective: To review clinical outcomes data for patients treated with oral ribavirin for noninfluenza respiratory viral infections (NIRVIs). Data Sources: MEDLINE, EMBASE, and PubMed Central (1972 to June 1, 2015) were queried with the following search term combinations: “Oral” AND “ribavirin” AND (“respiratory syncytial virus” OR “metapneumovirus” OR “parainfluenza” OR “coronavirus” OR “rhinovirus” OR “enterovirus” OR “adenovirus”). Study Selection and Data Extraction: Included studies must have characterized the clinical outcomes of a cohort of patients treated with oral ribavirin for symptomatic NIRVIs. Case reports and series with <5 cases, conference abstracts, and articles written in languages other than English were excluded. Data Synthesis: Of the 1256 unique reports, 15 met inclusion criteria: 12 retrospective, 3 prospective, and 3 comparative with untreated control groups. All studies except for 2 Middle East respiratory syndrome coronavirus (MERS-CoV) studies were in immunocompromised patients (9 malignancy/stem cell transplant, 4 lung transplant). The mortality rate ranged from 0% to 31% in malignancy/stem cell transplant recipients treated with oral ribavirin, and 1/108 (0.9%) ribavirin-treated lung transplant recipients died at 30 days. Three studies (one each for malignancy, lung transplant, and MERS-CoV) suggested a clinical outcomes benefit with oral ribavirin compared with supportive care alone; however, the nonrandomized design precludes efficacy determination. Hemolysis was the most common adverse reaction, occurring in 14% (54/375) of patients. Ribavirin was discontinued in 4% of patients secondary to adverse reactions. Conclusions: Oral ribavirin should be considered for the treatment of NIRVI in immunocompromised adults (malignancy/stem cell transplant or lung transplant) or adults with MERS-CoV.

Antiretroviral medication prescribing errors are common with hospitalization of HIV-infected patients

OBJECTIVES Errors in prescribing antiretroviral therapy (ART) often occur with the hospitalization of HIV-infected patients. The rapid identification and prevention of errors may reduce patient harm and healthcare-associated costs. METHODS A retrospective review of hospitalized HIV-infected patients was carried out between 1 January 2009 and 31 December 2011. Errors were documented as omission, underdose, overdose, duplicate therapy, incorrect scheduling and/or incorrect therapy. The time to error correction was recorded. Relative risks (RRs) were computed to evaluate patient characteristics and error rates. RESULTS A total of 289 medication errors were identified in 146/416 admissions (35%). The most common was drug omission (69%). At an error rate of 31%, nucleoside reverse transcriptase inhibitors were associated with an increased risk of error when compared with protease inhibitors (RR 1.32; 95% CI 1.04-1.69) and co-formulated drugs (RR 1.59; 95% CI 1.19-2.09). Of the errors, 31% were corrected within the first 24 h, but over half (55%) were never remedied. Admissions with an omission error were 7.4 times more likely to have all errors corrected within 24 h than were admissions without an omission. Drug interactions with ART were detected on 51 occasions. For the study population (n = 177), an increased risk of admission error was observed for black (43%) compared with white (28%) individuals (RR 1.53; 95% CI 1.16-2.03) but no significant differences were observed between white patients and other minorities or between men and women. CONCLUSION Errors in inpatient ART were common, and the majority were never detected. The most common errors involved omission of medication, and nucleoside reverse transcriptase inhibitors had the highest rate of prescribing error. Interventions to prevent and correct errors are urgently needed.

Predictors of Hospital Readmission in Patients Receiving Outpatient Parenteral Antimicrobial Therapy.

Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used, and unfortunately, readmissions during OPAT are common. The purpose of this study was to identify predictors of hospital readmission among patients receiving OPAT.

The Effect of a Piperacillin/Tazobactam Shortage on Antimicrobial Prescribing and Clostridium difficile Risk in 88 US Medical Centers

Background Anti-infective shortages are a pervasive problem in the United States. The objective of this study was to identify any associations between changes in prescribing of antibiotics that have a high risk for CDI during a piperacillin/tazobactam (PIP/TAZO) shortage and hospital-onset Clostridium difficile infection (HO-CDI) risk in 88 US medical centers. Methods We analyzed electronically captured microbiology and antibiotic use data from a network of US hospitals from July 2014 through June 2016. The primary outcome was HO-CDI rate and the secondary outcome was changes in antibiotic usage. We fit a Poisson model to estimate the risk of HO-CDI associated with PIP/TAZO shortage that were associated with increased high-risk antibiotic use while controlling for hospital characteristics. Results A total of 88 hospitals experienced PIP/TAZO shortage and 72 of them experienced a shift toward increased use of high-risk antibiotics during the shortage period. The adjusted relative risk (RR) of HO-CDI for hospitals experiencing a PIP/TAZO shortage was 1.03 (95% confidence interval [CI], .85-1.26; P = .73). The adjusted RR of HO-CDI for hospitals that both experienced a shortage and also showed a shift toward increased use of high-risk antibiotics was 1.30 (95% CI, 1.03-1.64; P < .05). Conclusions Hospitals that experienced a PIP/TAZO shortage and responded to that shortage by shifting antibiotic usage toward antibiotics traditionally known to place patients at greater risk for CDI experienced greater HO-CDI rates; this highlights an important adverse effect of the PIP/TAZO shortage and the importance of antibiotic stewardship when mitigating drug shortages.

Using Higher Doses to Compensate for Tubing Residuals in Extended-Infusion Piperacillin-Tazobactam

OBJECTIVE: To mathematically assess drug losses due to infusion line residuals and evaluate methods to compensate for drug loss due to residual volumes in intravenous pump tubing. DATA SOURCES: Literature was accessed through Ovid MEDLINE (1996-February 2013), using combinations of the search terms tubing residuals, residual volume, residual medication, intravenous infusions, intravenous injections, piperacillin, piperacillin-tazobactam, β-lactams, equipment design, infusion pumps, extended infusion, extended administration, and prolonged infusion. In addition, select reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles that involved extended-infusion piperacillin-tazobactam implementation strategies were included in the review. DATA SYNTHESIS: Infusion pump characteristics and tubing residuals can affect extended-infusion piperacillin-tazobactam dosing strategies. Two studies addressing tubing residuals were identified. Both studies recommended increasing infusion volumes to compensate for tubing residuals. One study also recommended decreasing infusion-line dead space by using alternative infusion pump systems. Study calculations suggest that higher doses of piperacillin-tazobactam may be used to account for medication left in tubing residuals if alternative infusion pump systems cannot be obtained, and increased infusion volumes are not an option. CONCLUSIONS: Extended-infusion piperacillin-tazobactam has been used as a method of maximizing pharmacodynamic target attainment. Use of higher doses of piperacillin-tazobactam may be a reasonable method to compensate for drug loss due to residual volumes in large-bore intravenous pump tubing.

A new practitioner’s guide to antimicrobial stewardship

It is commonly quoted that up to 50% of antimicrobial use is inappropriate.[1][1] Notably, antimicrobial use is the principal driver of resistance development, frequently causes adverse effects, and is associated with Clostridium difficile infection (CDI). At the same time, the approval of new

Evaluation of the Use of Novel Biomarkers to Augment Antimicrobial Stewardship Program Activities

As antimicrobial stewardship increasingly receives worldwide attention for improving patient care by optimizing antimicrobial therapy, programs are evaluating new tools that may augment antimicrobial stewardship activities. Biomarkers are objective, accurate, and reproducible measures that provide information about medical conditions. A systematic literature search using PubMed/MEDLINE databases was performed to evaluate the use of novel biomarkers as additions to the antimicrobial stewardship armamentarium. Procalcitonin may help clinicians discriminate between bacterial and viral infections, help with antimicrobial discontinuation decisions, and predict mortality. β‐d‐glucan, Candida albicans germ tube antibody, and galactomannan are useful in suspected fungal infections and may reduce inappropriate antifungal use. Adrenomedullin and soluble triggering receptor on myeloid cells‐1 may be useful for mortality prediction and the determination of a need for empiric antibacterials. Although studies evaluating these biomarkers are promising, these biomarkers are not without limitations and should be used in combination with clinical signs, symptoms, or other biomarkers. For successful implementation of biomarker use, stewardship programs should consider the populations most likely to benefit, without using them indiscriminately in all patients. Antimicrobial stewardship programs should facilitate education of clinicians through institutional guidelines to ensure the appropriate use and interpretation of these biomarkers.