Probabilistic microsimulation to examine the cost-effectiveness of hospital admission screening strategies for carbapenemase-producing enterobacteriaceae (CPE) in the United Kingdom.

BACKGROUND: Antimicrobial resistance has been recognised as a global threat with carbapenemase- producing-Enterobacteriaceae (CPE) as a prime example. CPE has similarities to COVID-19 where asymptomatic patients may be colonised representing a source for onward transmission. There are limited treatment options for CPE infection leading to poor outcomes and increased costs. Admission screening can prevent cross-transmission by pre-emptively isolating colonised patients. OBJECTIVE: We assess the relative cost-effectiveness of screening programmes compared with no- screening. METHODS: A microsimulation parameterised with NHS Scotland date was used to model scenarios of the prevalence of CPE colonised patients on admission. Screening strategies were (a) two-step screening involving a clinical risk assessment (CRA) checklist followed by microbiological testing of high-risk patients; and (b) universal screening. Strategies were considered with either culture or polymerase chain reaction (PCR) tests. All costs were reported in 2019 UK pounds with a healthcare system perspective. RESULTS: In the low prevalence scenario, no screening had the highest probability of cost-effectiveness. Among screening strategies, the two CRA screening options were the most likely to be cost-effective. Screening was more likely to be cost-effective than no screening in the prevalence of 1 CPE colonised in 500 admitted patients or more. There was substantial uncertainty with the probabilities rarely exceeding 40% and similar results between strategies. Screening reduced non-isolated bed-days and CPE colonisation. The cost of screening was low in relation to total costs. CONCLUSION: The specificity of the CRA checklist was the parameter with the highest impact on the cost-effectiveness. Further primary data collection is needed to build models with less uncertainty in the parameters.

Predictors of carbapenem-resistant Enterobacteriaceae (CRE) strains in patients with COVID-19 in the ICU ward: a retrospective case-control study.

OBJECTIVE: To identify carbapenem-resistant Enterobacteriaceae (CRE) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) and to determine whether they had different risk factors for the acquisition of CRE than patients without COVID-19. METHODS: This retrospective single-centre, case-control study enrolled patients with and without COVID-19. The demographic, clinical, infection, colonization and mortality data were compared between the two groups. RESULTS: A total of 38 patients with COVID-19 and 26 patients without COVID-19 were enrolled. The majority of isolates detected in COVID-19 patients were Klebsiella spp. Leukopenia at admission (odds ratio [OR] 4.70; 95% confidence interval [CI] 1.37, 16.10), invasive mechanical ventilation (OR 5.74; 95% CI 1.07, 30.63), carbapenem treatment (OR 5.09; 95% CI 1.21, 21.27) and corticosteroid treatment (OR 7.06; 95% CI 1.53, 32.39) were independent risk factors for CRE acquisition in COVID-19 patients. Intensive care unit (ICU) mortality was significantly higher in COVID-19 patients compared with patients without COVID-19 (OR 20.62; 95% CI 5.50, 77.23). Length of ICU stay increased the risk of death in patients with COVID-19 (subdistribution hazard ratio 3.81; 95% CI 1.33, 10.92). CONCLUSION: CRE strains were more common in patients with COVID-19 and they had different risks for CRE compared with patients without COVID-19.

Risk factors for isolation of carbapenem-resistant Enterobacterales from normally sterile sites and urine.

BACKGROUND: Invasive infections caused by carbapenem-resistant Enterobacterales (CRE) are of significant concern in health care settings. We assessed risk factors for a positive CRE culture from a sterile site (invasive infection) compared to isolation from urine in a large patient cohort in Atlanta from August 2011 to December 2015. METHODS: CRE cases required isolation, from urine or a normally-sterile site, of E. coli, Klebsiella spp., or Enterobacter spp. that were carbapenem-nonsusceptible (excluding ertapenem) and resistant to all third-generation cephalosporins tested. Risk factors were compared between patients with invasive and urinary infections using multivariable logistic regression. RESULTS: A total of 576 patients had at least 1 incident case of CRE, with 91 (16%) having an invasive infection. In multivariable analysis, the presence of a central venous catheter (OR 3.58; 95% CI: 2.06-6.23) or other indwelling device (OR 2.34; 95% CI: 1.35-4.06), and recent surgery within the last year (OR 1.81; 95% CI: 1.08-3.05) were associated with invasive infection when compared to urinary infection. DISCUSSION: Health care exposures and devices were associated with invasive infections in patients with CRE, suggesting that targeting indwelling catheters, including preventing unwarranted insertion or encouraging rapid removal, may be a potential infection control intervention. CONCLUSIONS: Future infection prevention efforts to decrease CRE cases in health care settings should focus on minimizing unnecessary devices.

Colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) in healthcare and community settings in Botswana: an antibiotic resistance in communities and hospitals (ARCH) study.

OBJECTIVES: Although extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) are a global challenge, data on these organisms in low- and middle-income countries are limited. In this study, we sought to characterize colonization data critical for greater antibiotic resistance surveillance efforts. METHODS: This study was conducted in three hospitals and six clinics in Botswana. We conducted ongoing surveillance of adult patients in hospitals and clinics and adults and children in the community. All participants underwent rectal swab sampling to identify ESCrE and CRE. RESULTS: Enrollment occurred from January 15, 2020, to September 4, 2020, but paused from April 2, 2020, to May 21, 2020, because of a countrywide COVID-19 lockdown. Of 5088 individuals approached, 2469 (49%) participated. ESCrE colonization prevalence was 30.7% overall (43% for hospital participants, 31% for clinic participants, 24% for adult community participants, and 26% for child community participants) (P <0.001). A total of 42 (1.7%) participants were colonized with CRE. CRE colonization prevalence was 1.7% overall (6.8% for hospital participants, 0.7% for clinic participants, 0.2% for adult community participants, and 0.5% for child community participants) (P <0.001). ESCrE and CRE prevalence varied substantially across regions and was significantly higher prelockdown versus postlockdown. CONCLUSIONS: ESCrE colonization was high in all settings in Botswana. CRE prevalence in hospitals was also considerable. Colonization prevalence varied by region and clinical setting and decreased after a countrywide lockdown.

Nosocomial outbreak of monoclonal VIM carbapenemase-producing Enterobacter cloacae complex in an intensive care unit during the COVID-19 pandemic: an integrated approach.

BACKGROUND: An outbreak of VIM carbapenemase-expressing Enterobacter cloacae complex occurred between March and October 2020 in an intensive care unit (ICU) of a tertiary care and teaching hospital in France. At the same time, the hospital was facing the COVID-19 first wave. AIM: To describe the management of an outbreak caused by a VIM-producing Enterobacter cloacae complex strain during the COVID-19 pandemic in an ICU and to show the importance of an integrated approach. METHODS: A multi-focal investigation was conducted including descriptive and molecular epidemiology, environmental screening, and assessment of infection prevention and control measures. FINDINGS: A total of 14 cases were identified in this outbreak with a high attributable mortality rate (85.7%). The outbreak management was coordinated by a crisis cell, and involved the implementation of multi-disciplinary actions such as: enhanced hygiene measures, microbiological and molecular analysis of patients and environmental E. cloacae complex strains, and simulation-based teaching. All 23 E. cloacae complex strains isolated from patients and environment samples belonged to multi-locus sequence type ST78 and carried bla-VIM4 gene. Using Fourier transform infrared spectroscopy, all but two isolates were also found to belong to a single cluster. Although the source of this outbreak could not be pinpointed, the spread of the strain was controlled thanks to this multi-focal approach and multi-disciplinary implementation. CONCLUSION: This investigation highlighted the usefulness of Fourier transform infra-red spectroscopy in the rapid typing of outbreak strains as well as the importance of an integrated approach to successfully fight against multidrug-resistant micro-organism dissemination and healthcare-associated infections.

Nosocomial cluster of carbapenemase-producing Enterobacter cloacae in an intensive care unit dedicated COVID-19.

Concomitant prevention of SARS-CoV-2 and extensively drug-resistant bacteria transmission is a difficult challenge in intensive care units dedicated to COVID-19 patients. We report a nosocomial cluster of four patients carrying NDM-1 plasmid-encoded carbapenemase-producing Enterobacter cloacae. Two main factors may have contributed to cross-transmission: misuse of gloves and absence of change of personal protective equipment, in the context of COVID-19-associated shortage. This work highlights the importance of maintaining infection control measures to prevent CPE cross-transmission despite the difficult context and that this type of outbreak can potentially involve several species of Enterobacterales.

Protective effect of SARS-CoV-2 preventive measures against ESKAPE and Escherichia coli infections.

BACKGROUND/OBJECTIVES: We investigated whether behavioral precautions adopted during Coronavirus disease (COVID-19) pandemic also influenced the spreading and multidrug resistance (MDR) of ESKAPEEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii [AB], Pseudomonas aeruginosa, Enterobacter spp and Escherichia Coli, [EC]) among Intensive Care Unit (ICU) patients. SUBJECTS/METHODS: We performed a single-center retrospective study in adult patients admitted to our COVID-19-free surgical ICU. Only patients staying in ICU for more than 48 hours were included. The ESKAPEEc infections recorded during the COVID-19 period (June 1, 2020 - February 28, 2021) and in the corresponding pre-pandemic period (June 1, 2019 - February 28, 2020) were compared. An interrupted time series analysis was performed to rule out possible confounders. RESULTS: Overall, 173 patients in the COVID-19 period and 132 in the pre-COVID-19 period were investigated. The ESKAPEEc infections were documented in 23 (13.3%) and 35 (26.5%) patients in the pandemic and the pre-pandemic periods, respectively (p = 0.005). Demographics, diagnosis, comorbidities, type of surgery, Simplified Acute Physiology Score II, length of mechanical ventilation, hospital and ICU length of stay, ICU death rate, and 28-day hospital mortality were similar in the two groups. In comparison with the pre-pandemic period, no AB was recorded during COVID-19 period, (p = 0.017), while extended-spectrum beta-lactamase-producing EC infections significantly decreased (p = 0.017). Overall, the ESKAPEEc isolates during pandemic less frequently exhibited multidrug-resistant (p = 0.014). CONCLUSIONS: These findings suggest that a robust adherence to hygiene measures together with human contact restrictions in a COVID-19 free ICU might also restrain the transmission of ESKAPEEc pathogens.

Carbapenemase-producing Enterobacterales infections in COVID-19 patients.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) infections have been occasionally described in patients with coronavirus disease-19 (COVID-19). We assess the clinical features and outcome of these infections. METHODS: In this retrospective single-centre, case-control study, we included 54 patients with CPE infection: 30 case-patients (COVID-19) and 24 controls (non-COVID-19), collected between March and May 2020. We compared the epidemiological, clinical features, and outcome between cases and controls. RESULTS: CPE infection was more frequent in COVID-19 patients than in controls (1.1 vs. 0.5%, p = .005). COVID-19 patients were younger, had a lower frequency of underlying diseases (p = .01), and a lower median Charlson score (p = .002). Predisposing factors such as antimicrobial use, mechanical ventilation, or ICU admission, were more frequent in COVID-19 patients (p < .05). There were 73 episodes of infection (42 cases and 31 controls) that were more frequently hospital-acquired and diagnosed at the ICU in COVID-19 patients (p < .001). Urinary tract was the most common source of infection (47.9%), followed by pneumonia (23.3%). The frequency of severe sepsis or shock (p = .01) as well as the median SOFA score (p = .04) was higher in cases than in controls. Klebsiella pneumoniae (80.8%), Serratia marcescens (11%) and Enterobacter cloacae (4.1%) were the most common bacteria in both groups (KPC 56.2%, OXA-48 26% and VIM 17.8%). Overall 30-d mortality rate of COVID-19 patients and controls was 30 and 16.7%, respectively (p = .25). CONCLUSIONS: COVID-19 patients have an increased risk of CPE infections, which usually present as severe, nosocomial infections, appearing in critically-ill patients and associated with a high mortality.

Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital.

BACKGROUND: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE). OBJECTIVES: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19. METHODS: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis. RESULTS: We identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data. CONCLUSIONS: While CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.

Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stewardship.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Carbapenemase-producing Enterobacterales outbreak: Another dark side of COVID-19.

In the hospital department dedicated to COVID-19-patient, infection prevention and control measures were upgraded. Therefore, the cross-transmission of other micro-organisms was thought unlikely to occur. However, we report an outbreak of NDM-5-producing Escherichia. coli in a 12-beds ICU dedicated to COVID-19 patients. This outbreak involved 6 patients of which 5 were asymptomatic carriers and 1 was infected. Several findings might have contributed to cross-transmission including the multiple-bedroom configuration of the department, uncomplete compliance for standard and contact precautions, overwork due to the burden of the disease, lack of training of staff for the care of ICU-patients, and misuse of gloves. Furthermore, as infection prevention and control measures were thought to be applied, contact patients were not screened for eXDR carriage. Applying rigorously standard and contact precautions and performing screening in contact patients when indicated must be the rules in COVID-19 wards.

Bloodstream infections in critically ill patients with COVID-19.

BACKGROUND: Little is known about the incidence and risk of intensive care unit (ICU)-acquired bloodstream infections (BSI) in critically ill patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: This retrospective, single-centre study was conducted in Northern Italy. The primary study objectives were as follows: (a) to assess the incidence rate of ICU-acquired BSI and (b) to assess the cumulative risk of developing ICU-acquired BSI. RESULTS: Overall, 78 critically ill patients with COVID-19 were included in the study. Forty-five episodes of ICU-acquired BSI were registered in 31 patients, with an incidence rate of 47 episodes (95% confidence interval [CI] 35-63) per 1000 patient-days at risk. The estimated cumulative risk of developing at least one BSI episode was of almost 25% after 15 days at risk and possibly surpassing 50% after 30 days at risk. In multivariable analysis, anti-inflammatory treatment was independently associated with the development of BSI (cause-specific hazard ratio [csHR] 1.07 with 95% CI 0.38-3.04 for tocilizumab, csHR 3.95 with 95% CI 1.20-13.03 for methylprednisolone and csHR 10.69 with 95% CI 2.71-42.17 for methylprednisolone plus tocilizumab, with no anti-inflammatory treatment as the reference group; overall P for the dummy variable = 0.003). CONCLUSIONS: The incidence rate of BSI was high, and the cumulative risk of developing BSI increased with ICU stay. Further study will clarify if the increased risk of BSI we detected in COVID-19 patients treated with anti-inflammatory drugs is outweighed by the benefits of reducing any possible pro-inflammatory dysregulation induced by SARS-CoV-2.