Pranita D. Tamma

Safety of influenza vaccination during pregnancy

The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommends routine influenza vaccination for all women who are or will be pregnant during the influenza season. During seasonal influenza epidemics, during previous pandemics, and with the current influenza A (H1N1) pandemic, pregnancy places otherwise healthy women at increased risk for serious complications from influenza, including death. Inactivated influenza vaccine can be safely and effectively administered during any trimester of pregnancy. No study to date has demonstrated an increased risk of either maternal complications or adverse fetal outcomes associated with inactivated influenza vaccination. Moreover, no scientific evidence exists that thimerosal-containing vaccines are a cause of adverse events among children born to women who received influenza vaccine during pregnancy. In this article, we review the evidentiary basis for the recommendation of vaccination of all women who will be pregnant during the influenza season and safety data of influenza vaccination during pregnancy.

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

SUMMARY Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria.

Carbapenem Therapy Is Associated With Improved Survival Compared With Piperacillin-Tazobactam for Patients With Extended-Spectrum β-Lactamase Bacteremia

BACKGROUND The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem. METHODS Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. RESULTS A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45). CONCLUSIONS PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents.

Chlorhexidine use in the Neonatal Intensive Care Unit: Results from a National Survey

Infection prevention guidelines do not endorse chlorhexidine gluconate (CHG) use in neonates who are less than 2 months old. A survey of US neonatology program directors revealed that most neonatal intensive care units use CHG, often with some restrictions. Prospective studies are needed to further address concerns regarding the safety of CHG in patients in the neonatal intensive care unit.

The Use of Cefepime for Treating AmpC β-lactamase Producing Enterobacteriaceae

BACKGROUND  AmpC β-lactamase-producing organisms are associated with significant morbidity and mortality. Induction of resistance to third-generation cephalosporins after exposure to these agents complicates treatment options and carbapenems are considered optimal therapy. The role of cefepime, however, remains unclear. Our objective was to compare clinical outcomes for patients receiving cefepime compared with meropenem for invasive infections caused by organisms expressing AmpC β-lactamases. METHODS  Hospitalized patients with blood, bronchoalveolar lavage, or intra-abdominal fluid cultures growing Enterobacter spp, Serratia spp, or Citrobacter spp were evaluated using the cefotetan-boronic acid disk test and the cefotetan-cloxacillin Etest to identify organisms with AmpC β-lactamase production from February 2010 to January 2011. In patients with organisms hyperproducing AmpC β-lactamases (positive by both methods), clinical outcomes for patients receiving cefepime or meropenem therapy were compared. To minimize the possibility of treatment selection bias, 1:1 nearest neighbor propensity score matching was performed prior to regression analysis. RESULTS  Of 399 patients meeting eligibility criteria, 96 (24%) had confirmed infections with AmpC β-lactamase-producing organisms. Propensity score matching of patients infected with AmpC β-lactamase-positive organisms treated with cefepime or meropenem yielded 32 well-balanced patient pairs with no difference in 30-day mortality (odds ratio, 0.63; 95% confidence interval [CI], .23-2.11; P = .36) or length of hospital stay after infection (relative risk, 0.96; 95% CI, .79-1.26; P = .56) between the 2 groups. CONCLUSIONS  Cefepime may be a reasonable option for the treatment of invasive infections due to AmpC β-lactamase-producing organisms, particularly when adequate source control is achieved.

Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials

BackgroundThe emergence of multi-drug resistant Gram-negatives (MDRGNs) coupled with an alarming scarcity of new antibiotics has forced the optimization of the therapeutic potential of available antibiotics. To exploit the time above the minimum inhibitory concentration mechanism of β-lactams, prolonging their infusion may improve outcomes. The primary objective of this meta-analysis was to determine if prolonged β-lactam infusion resulted in decreased mortality and improved clinical cure compared to intermittent β-lactam infusion.MethodsRelevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL. Heterogeneity was assessed qualitatively, in addition to I2 and Chi-square statistics. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using Mantel-Haenszel random-effects models.ResultsFourteen randomized controlled trials (RCTs) were included. Prolonged infusion β-lactams were not associated with decreased mortality (n= 982; RR 0.92; 95% CI:0.61-1.37) or clinical cure (n = 1380; RR 1.00 95% CI:0.94-1.06) compared to intermittent infusions. Subgroup analysis for β-lactam subclasses and equivalent total daily β-lactam doses yielded similar results. Most studies had notable methodological flaws.ConclusionsNo clinical advantage was observed for prolonged infusion β-lactams. The limited number of studies with MDRGNs precluded evaluation of prolonged infusion of β-lactams for this subgroup. A large, multicenter RCT with critically ill patients infected with MDRGNs is needed.

Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia

Background. Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative. Methods. We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify &bgr;-lactamase-encoding genes. Results. There were 83 unique episodes of monomicrobial CRE bacteremia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE. The majority of CP-CRE isolates were bla KPC (92%), followed by bla NDM (5%) and bla OXA-48-type (3%). CP-CRE isolates were more likely to have meropenem minimum inhibitory concentrations (MICs) ≥16 µg/mL, while non-CP-CRE isolates were more likely to have meropenem MICs ⩽1 µg/mL (P value < .001). A total of 18 (22%) patients died within 14 days, including 12 (32%) in the CP-CRE group and 6 (13%) in the non-CP-CRE group. Adjusting for severity of illness on day 1 of bacteremia, underlying medical conditions, and differences in antibiotic treatment administered, the odds of dying within 14 days were more than 4 times greater for CP-CRE compared with non-CP-CRE bacteremic patients (adjusted odds ratio, 4.92; 95% confidence interval, 1.01–24.81). Conclusion. Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.

Clostridium difficile Infection in Children: Current State and Unanswered Questions

The incidence of Clostridium difficile infection (CDI) in children has increased over the past decade. In recent years, new and intriguing data on pediatric CDI have emerged. Community-onset infections are increasingly recognized, even in children who have not previously received antibiotics. A hypervirulent strain is responsible for up to 20% of pediatric CDI cases. Unique risk factors for CDI in children have been identified. Advances in diagnostic testing strategies, including the use of nucleic acid amplification tests, have raised new questions about the optimal approach to diagnosing CDI in children. Novel therapeutic options are available for adult patients with CDI, raising questions about the use of these agents in children. Updated recommendations about infection prevention and control measures are now available. We summarize these recent developments in pediatric CDI in this review and also highlight remaining knowledge gaps that should be addressed in future research efforts.

Sustained Savings from a Longitudinal Cost Analysis of an Internet-Based Preapproval Antimicrobial Stewardship Program

OBJECTIVE To evaluate an internet-based preapproval antimicrobial stewardship program for sustained reduction in antimicrobial prescribing and resulting cost savings. DESIGN Retrospective cohort study and cost analysis. METHODS Review of all doses and charges of antimicrobials dispensed to patients over 6 years (July 1, 2005-June 30, 2011) at a tertiary care pediatric hospital. RESULTS Restricted antimicrobials account for 26% of total doses but 81% of total antimicrobial charges. Winter months (November-February) and the oncology and infant and toddler units were associated with the highest antimicrobial charges. Five restricted drugs accounted for the majority (54%) of charges but only 6% of doses. With an average approval rate of 91.5% (95% confidence interval [CI], 91.1%-91.9%), the preapproval antibiotic stewardship program saved

An Outbreak of Extended-Spectrum β-Lactamase–Producing Klebsiella pneumoniae in a Neonatal Intensive Care Unit

103,787 (95% CI,