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.

COVID-19 influences lung microbiota dynamics and favors the emergence of rare infectious diseases: A case report of Hafnia Alvei pneumonia.

The coronavirus disease 2019 causes a wide degree of organ dysfunction and is associated with bacterial secondary infections. We reported lung microbiota dynamics in a critically ill patient with coronavirus disease 2019, who developed severe Hafnia alvei ventilator-associated pneumonia and required extracorporeal membrane oxygenation support.

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.

Sinusitis caused by a rare organism, Cedecea lapagei.

A 45-year-old man presented with acute sinusitis. He was treated with a 10-day course of trimethoprim/sulfamethoxazole, and a subsequent 14-day course of amoxicillin-clavulanate with no improvement in symptoms. Culture of purulent nasal secretions revealed the rare enterobacter Cedecea lapagei The patient had complete resolution of his symptoms after a 14-day course of gentamicin/dexamethasone nasal rinses. Emerging pathogens have been a timeless concern for physicians, as witnessed by the current SARS-CoV-2 outbreak. C. lapagei has been reported to cause human infection only a dozen times since its discovery, all in severely compromised patients. This is the first documented case of sinusitis reported with C. lapagei and may portend a rising prevalence of disease burden in the general population. This case demonstrates the necessity of obtaining cultures when standard antibiotics result in treatment failure.