Brigid Wilson

Intestinal Carriage of Carbapenemase-Producing Organisms: Current Status of Surveillance Methods

SUMMARY Carbapenemases have become a significant mechanism for broad-spectrum β-lactam resistance in Enterobacteriaceae and other Gram-negative bacteria such as Pseudomonas and Acinetobacter spp. Intestinal carriage of carbapenemase-producing organisms (CPOs) is an important source of transmission. Isolation of carriers is one strategy that can be used to limit the spread of these bacteria. In this review, we critically examine the clinical performance, advantages, and disadvantages of methods available for the detection of intestinal carriage of CPOs. Culture-based methods (Centers for Disease Control and Prevention [CDC] protocols, chromogenic media, specialized agars, and double-disk synergy tests) for detecting carriage of CPOs are convenient due to their ready availability and low cost, but their limited sensitivity and long turnaround time may not always be optimal for infection control practices. Contemporary nucleic acid amplification techniques (NAATs) such as real-time PCR, hybridization assays, loop-mediated isothermal amplification (LAMP), or a combined culture and NAAT approach may provide fast results and/or added sensitivity and specificity compared with culture-based methods. Infection control practitioners and clinical microbiologists should be aware of the strengths and limitations of available methods to determine the most suitable approach for their medical facility to fit their infection control needs.

Contamination of Health Care Personnel During Removal of Personal Protective Equipment

IMPORTANCE Contamination of the skin and clothing of health care personnel during removal of personal protective equipment (PPE) contributes to dissemination of pathogens and places personnel at risk for infection. OBJECTIVES To determine the frequency and sites of contamination on the skin and clothing of personnel during PPE removal and to evaluate the effect of an intervention on the frequency of contamination. DESIGN, SETTING, AND PARTICIPANTS We conducted a point-prevalence study and quasi-experimental intervention from October 28, 2014, through March 31, 2015. Data analysis began November 17, 2014, and ended April 21, 2015. Participants included a convenience sample of health care personnel from 4 Northeast Ohio hospitals who conducted simulations of contaminated PPE removal using fluorescent lotion and a cohort of health care personnel from 7 study units in 1 medical center that participated in a quasi-experimental intervention that included education and practice in removal of contaminated PPE with immediate visual feedback based on fluorescent lotion contamination of skin and clothing. MAIN OUTCOMES AND MEASURES The primary outcomes were the frequency and sites of contamination on skin and clothing of personnel after removal of contaminated gloves or gowns at baseline vs after the intervention. A secondary end point focused on the correlation between contamination of skin with fluorescent lotion and bacteriophage MS2, a nonpathogenic, nonenveloped virus. RESULTS Of 435 glove and gown removal simulations, contamination of skin or clothing with fluorescent lotion occurred in 200 (46.0%), with a similar frequency of contamination among the 4 hospitals (range, 42.5%-50.3%). Contamination occurred more frequently during removal of contaminated gloves than gowns (52.9% vs 37.8%, P = .002) and when lapses in technique were observed vs not observed (70.3% vs 30.0%, P < .001). The intervention resulted in a reduction in skin and clothing contamination during glove and gown removal (60.0% before the intervention vs 18.9% after, P < .001) that was sustained after 1 and 3 months (12.0% at both time points, P < .001 compared with before the intervention). During simulations of contaminated glove removal, the frequency of skin contamination was similar with fluorescent lotion and bacteriophage MS2 (58.0% vs 52.0%, P = .45). CONCLUSIONS AND RELEVANCE Contamination of the skin and clothing of health care personnel occurs frequently during removal of contaminated gloves or gowns. Educational interventions that include practice with immediate visual feedback on skin and clothing contamination can significantly reduce the risk of contamination during removal of PPE.

Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply "precision medicine" to antimicrobial chemotherapy?

ABSTRACT Introduction: For the past three decades, carbapenems played a central role in our antibiotic armamentarium, trusted to effectively treat infections caused by drug-resistant bacteria. The utility of this class of antibiotics has been compromised by the emergence of resistance especially among Enterobacteriaceae. Areas covered: We review the current mainstays of pharmacotherapy against infections caused by carbapenem-resistant Enterobacteriaceae (CRE) including tigecycline, aminoglycosides, and rediscovered ‘old’ antibiotics such as fosfomycin and polymyxins, and discuss their efficacy and potential toxicity. We also summarize the contemporary clinical experience treating CRE infections with antibiotic combination therapy. Finally, we discuss ceftazidime/avibactam and imipenem/relebactam, containig a new generation of beta-lactamase inhibitors, which may offer alternatives to treat CRE infections. We critically evaluate the published literature, identify relevant clinical trials and review documents submitted to the United States Food and Drug Administration. Expert opinion: Defining the molecular mechanisms of resistance and applying insights about pharmacodynamic and pharmacokinetic properties of antibiotics, in order to maximize the impact of old and new therapeutic approaches should be the new paradigm in treating infections caused by CRE. A concerted effort is needed to carry out high-quality clinical trials that: i) establish the superiority of combination therapy vs. monotherapy; ii) confirm the role of novel beta-lactam/beta-lactamase inhibitor combinations as therapy against KPC- and OXA-48 producing Enterobacteriaceae; and, iii) evaluate new antibiotics active against CRE as they are introduced into the clinic.

Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae?

ABSTRACT Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log10-CFU decrease for all groups that had CAZ-AVI with ATM (8 μg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log10-CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae.

Exploring the Role of Residue 228 in Substrate and Inhibitor Recognition by VIM Metallo-β-lactamases.

β-Lactamase inhibitors (BLIs) restore the efficacy of otherwise obsolete β-lactams. However, commercially available BLIs are not effective against metallo-β-lactamases (MBLs), which continue to be disseminated globally. One group of the most clinically important MBLs is the VIM family. The discovery of VIM-24, a natural variant of VIM-2, possessing an R228L substitution and a novel phenotype, compelled us to explore the role of this position and its effects on substrate specificity. We employed mutagenesis, biochemical and biophysical assays, and crystallography. VIM-24 (R228L) confers enhanced resistance to cephems and increases the rate of turnover compared to that of VIM-2 (kcat/KM increased by 6- and 10-fold for ceftazidime and cefepime, respectively). Likely the R → L substitution relieves steric clashes and accommodates the C3N-methyl pyrrolidine group of cephems. Four novel bisthiazolidine (BTZ) inhibitors were next synthesized and tested against these MBLs. These inhibitors inactivated VIM-2 and VIM-24 equally well (Ki* values of 40-640 nM) through a two-step process in which an initial enzyme (E)-inhibitor (I) complex (EI) undergoes a conformational transition to a more stable species, E*I. As both VIM-2 and VIM-24 were inhibited in a similar manner, the crystal structure of a VIM-2-BTZ complex was determined at 1.25 Å and revealed interactions of the inhibitor thiol with the VIM Zn center. Most importantly, BTZs also restored the activity of imipenem against Klebsiella pneumoniae and Pseudomonas aeruginosa in whole cell assays producing VIM-24 and VIM-2, respectively. Our results suggest a role for position 228 in defining the substrate specificity of VIM MBLs and show that BTZ inhibitors are not affected by the R228L substitution.

A Multicenter Randomized Trial to Determine the Effect of an Environmental Disinfection Intervention on the Incidence of Healthcare-Associated Clostridium difficile Infection

OBJECTIVE To determine the impact of an environmental disinfection intervention on the incidence of healthcare-associated Clostridium difficile infection (CDI). DESIGN A multicenter randomized trial. SETTING In total,16 acute-care hospitals in northeastern Ohio participated in the study. INTERVENTION We conducted a 12-month randomized trial to compare standard cleaning to enhanced cleaning that included monitoring of environmental services (EVS) personnel performance with feedback to EVS and infection control staff. We assessed the thoroughness of cleaning based on fluorescent marker removal from high-touch surfaces and the effectiveness of disinfection based on environmental cultures for C. difficile. A linear mixed model was used to compare CDI rates in the intervention and postintervention periods for control and intervention hospitals. The primary outcome was the incidence of healthcare-associated CDI. RESULTS Overall, 7 intervention hospitals and 8 control hospitals completed the study. The intervention resulted in significantly increased fluorescent marker removal in CDI and non-CDI rooms and decreased recovery of C. difficile from high-touch surfaces in CDI rooms. However, no reduction was observed in the incidence of healthcare-associated CDI in the intervention hospitals during the intervention and postintervention periods. Moreover, there was no correlation between the percentage of positive cultures after cleaning of CDI or non-CDI rooms and the incidence of healthcare-associated CDI. CONCLUSIONS An environmental disinfection intervention improved the thoroughness and effectiveness of cleaning but did not reduce the incidence of healthcare-associated CDI. Thus, interventions that focus only on improving cleaning may not be sufficient to control healthcare-associated CDI. Infect Control Hosp Epidemiol 2017;38:777-783.

Are health care personnel trained in correct use of personal protective equipment

Effective use of personal protective equipment (PPE) is essential to protect personnel and patients in health care settings. However, in a survey of 222 health care personnel, PPE training was often suboptimal with no requirement for demonstration of proficiency. Fourteen percent of physicians reported no previous training in use of PPE.

An intervention to reduce health care personnel hand contamination during care of patients with Clostridium difficile infection

In a quasi-experimental study, an educational intervention to improve the technique for personal protective equipment (PPE) removal in conjunction with disinfection of gloves before removal of PPE reduced acquisition of Clostridium difficile spores on the hands of health care personnel caring for patients with C difficile infection.

Do medical students receive training in correct use of personal protective equipment

ABSTRACT Background: Healthcare personnel often use incorrect technique for donning and doffing of personal protective equipment (PPE). Objective: We tested the hypothesis that medical students receive insufficient training on correct methods for donning and doffing PPE. Methods: We conducted a cross-sectional survey of medical students on clinical rotations at two teaching hospitals to determine the type of training they received in PPE technique. The students performed simulations of contaminated PPE removal with fluorescent lotion on gloves and were assessed for correct PPE technique and skin and/or clothing contamination. To obtain additional information on PPE training during medical education, residents, fellows, and attending physicians completed written questionnaires on PPE training received during medical school and on knowledge of PPE protocols recommended by the Centers for Disease Control and Prevention. Results: Of 27 medical students surveyed, only 11 (41%) reported receiving PPE training, and none had received training requiring demonstration of proficiency. During simulations, 25 of 27 (92.5%) students had one or more lapses in technique and 12 (44%) contaminated their skin with fluorescent lotion. For 100 residents, fellows and attending physicians representing 67 different medical schools, only 53% reported receiving training in use of PPE and only 39% selected correct donning and doffing sequence. Conclusions: Our findings suggest that there is a need for development of effective strategies to train medical students in correct use of PPE. Abbreviations: PPE: Personal protective equipment; MRSA: Methicillin-resistant Staphylococcus aureus; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; WHO: World Health Organization; CDC: Centers for Disease Control and Prevention; OSCE: Objective structured clinical examination

A Novel, Sporicidal Formulation of Ethanol for Glove Decontamination to Prevent Clostridium difficile Hand Contamination During Glove Removal.

Decontamination of gloves before removal could reduce the risk for contamination of hands of personnel caring for patients with Clostridium difficile infection. We demonstrated that a novel sporicidal formulation of ethanol rapidly reduced C. difficile spores on gloved hands without adverse odor, respiratory irritation, or staining of clothing.