Antimicrobial susceptibility patterns of respiratory Gram-negative bacterial isolates from COVID-19 patients in Switzerland.

BACKGROUND: Bacterial superinfections associated with COVID-19 are common in ventilated ICU patients and impact morbidity and lethality. However, the contribution of antimicrobial resistance to the manifestation of bacterial infections in these patients has yet to be elucidated. METHODS: We collected 70 Gram-negative bacterial strains, isolated from the lower respiratory tract of ventilated COVID-19 patients in Zurich, Switzerland between March and May 2020. Species identification was performed using MALDI-TOF; antibiotic susceptibility profiles were determined by EUCAST disk diffusion and CLSI broth microdilution assays. Selected Pseudomonas aeruginosa isolates were analyzed by whole-genome sequencing. RESULTS: Pseudomonas aeruginosa (46%) and Enterobacterales (36%) comprised the two largest etiologic groups. Drug resistance in P. aeruginosa isolates was high for piperacillin/tazobactam (65.6%), cefepime (56.3%), ceftazidime (46.9%) and meropenem (50.0%). Enterobacterales isolates showed slightly lower levels of resistance to piperacillin/tazobactam (32%), ceftriaxone (32%), and ceftazidime (36%). All P. aeruginosa isolates and 96% of Enterobacterales isolates were susceptible to aminoglycosides, with apramycin found to provide best-in-class coverage. Genotypic analysis of consecutive P. aeruginosa isolates in one patient revealed a frameshift mutation in the transcriptional regulator nalC that coincided with a phenotypic shift in susceptibility to ß-lactams and quinolones. CONCLUSIONS: Considerable levels of antimicrobial resistance may have contributed to the manifestation of bacterial superinfections in ventilated COVID-19 patients, and may in some cases mandate consecutive adaptation of antibiotic therapy. High susceptibility to amikacin and apramycin suggests that aminoglycosides may remain an effective second-line treatment of ventilator-associated bacterial pneumonia, provided efficacious drug exposure in lungs can be achieved.

Pathogenic characteristics of sputum and bronchoalveolar lavage fluid samples from patients with lower respiratory tract infection in a large teaching hospital in China: a retrospective study.

BACKGROUND: Lower respiratory tract infection (LRIs) is very common both in terms of community-acquired infection and hospital-acquired infection. Sputum and bronchoalveolar lavage fluid (BALF) are the most important specimens obtained from patients with LRI. The choice of antibiotic with which to treat LRI usually depends on the antimicrobial sensitivity of bacteria isolated from sputum and BALF. However, differences in the antimicrobial sensitivity of pathogens isolated from sputum and BALF have not been evaluated. METHODS: A retrospective study was conducted to analyze the differences between sputum and BALF samples in terms of pathogen isolation and antimicrobial sensitivity in hospitalized patients with LRI. RESULTS: Between 2013 and 2015, quality evaluation of sputum samples was not conducted before performing sputum culture; however, between 2016 and 2018, quality evaluation of sputum samples was conducted first, and only quality-assured samples were cultured. The numbers of sputum and BALF in 2013-2015 were 15,549 and 1671, while those in 2016-2018 were 12,055 and 3735, respectively. The results of pathogen culture showed that Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Hemophilus influenzae, Escherichia coli, Stenotrophomonas maltophilia, and Streptococcus pneumoniae were in the top ten pathogens isolated from sputum and BALF. An antimicrobial susceptibility test showed that the susceptibility of BALF isolates to most antibiotics was higher compared with the susceptibility of sputum isolates, especially after quality control of sputum samples (2016-2018). CONCLUSIONS: Our findings suggest that caution is needed in making therapeutic choices for patients with LRI when using antimicrobial sensitivity results from sputum isolates as opposed to BALF isolates.

Secondary bacterial infection in COVID-19 patients is a stronger predictor for death compared to influenza patients.

Secondary bacterial infections are a potentially fatal complication of influenza infection. We aimed to define the impact of secondary bacterial infections on the clinical course and mortality in coronavirus disease 2019 (COVID-19) patients by comparison with influenza patients. COVID-19 (n = 642) and influenza (n = 742) patients, admitted to a large tertiary center in Israel and for whom blood or sputum culture had been taken were selected for this study. Bacterial culture results, clinical parameters, and death rates were compared. COVID-19 patients had higher rates of bacterial infections than influenza patients (12.6% vs. 8.7%). Notably, the time from admission to bacterial growth was longer in COVID-19 compared to influenza patients (4 (1-8) vs. 1 (1-3) days). Late infections (> 48 h after admission) with gram-positive bacteria were more common in COVID-19 patients (28% vs. 9.5%). Secondary infection was associated with a higher risk of death in both patient groups 2.7-fold (1.22-5.83) for COVID-19, and 3.09-fold (1.11-7.38) for Influenza). The association with death remained significant upon adjustment to age and clinical parameters in COVID-19 but not in influenza infection. Secondary bacterial infection is a notable complication associated with worse outcomes in COVID-19 than influenza patients. Careful surveillance and prompt antibiotic treatment may benefit selected patients.

Clinical characteristics and risk factors for the isolation of multi-drug-resistant Gram-negative bacteria from critically ill patients with COVID-19.

BACKGROUND: We investigated the clinical characteristics and risk factors for the isolation of multi-drug-resistant (MDR) Gram-negative bacteria (GNB) from critically ill COVID-19 patients. METHODS: We retrospectively matched (1:2) critical COVID-19 patients with one or more MDR GNB from any clinical specimen (cases), with those with no MDR GNB isolates (controls). RESULTS: Seventy-eight cases were identified (4.5 per 1000 intensive care unit (ICU) days, 95% confidence interval (CI) 3.6-5.7). Of 98 MDR GNB isolates, the most frequent species were Stenotrophomonas maltophilia (24, 24.5%), and Klebsiella pneumoniae (23, 23.5%). Two (8.7%) K. pneumoniae, and six (85.7%) Pseudomonas aeruginosa isolates were carbapenem resistant. A total of 24 (24.5%) isolates were not considered to be associated with active infection. Those with active infection received appropriate antimicrobial agents within a median of one day. The case group had significantly longer median central venous line days, mechanical ventilation days, and hospital length of stay (P<0.001 for each). All-cause mortality at 28 days was not significantly different between the two groups (P=0.19). Mechanical ventilation days (adjusted odds ratio 1.062, 95% CI 1.012-1.114; P=0.015), but not receipt of corticosteroids or tocilizumab, was independently associated with the isolation of MDR GNB. There was no association between MDR GNB and 28-day all-cause mortality (adjusted odds ratio 2.426, 95% CI 0.833-7.069; P= 0.104). CONCLUSION: In critically ill COVID-19 patients, prevention of MDR GNB colonization and infections requires minimizing the use of invasive devices, and to remove them as soon as their presence is no longer necessary.

A multicenter analysis of the clinical microbiology and antimicrobial usage in hospitalized patients in the US with or without COVID-19.

BACKGROUND: Past respiratory viral epidemics suggest that bacterial infections impact clinical outcomes. There is minimal information on potential co-pathogens in patients with coronavirus disease-2019 (COVID-19) in the US. We analyzed pathogens, antimicrobial use, and healthcare utilization in hospitalized US patients with and without severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). METHODS: This multicenter retrospective study included patients with > 1 day of inpatient admission and discharge/death between March 1 and May 31, 2020 at 241 US acute care hospitals in the BD Insights Research Database. We assessed microbiological testing data, antimicrobial utilization in admitted patients with ≥24 h of antimicrobial therapy, and length of stay (LOS). RESULTS: A total of 141,621 patients were tested for SARS-CoV-2 (17,003 [12.0%] positive) and 449,339 patients were not tested. Most (> 90%) patients tested for SARS-CoV-2 had additional microbiologic testing performed compared with 41.9% of SARS-CoV-2-untested patients. Non-SARS-CoV-2 pathogen rates were 20.9% for SARS-CoV-2-positive patients compared with 21.3 and 27.9% for SARS-CoV-2-negative and -untested patients, respectively. Gram-negative bacteria were the most common pathogens (45.5, 44.1, and 43.5% for SARS-CoV-2-positive, -negative, and -untested patients). SARS-CoV-2-positive patients had higher rates of hospital-onset (versus admission-onset) non-SARS-CoV-2 pathogens compared with SARS-CoV-2-negative or -untested patients (42.4, 22.2, and 19.5%, respectively), more antimicrobial usage (68.0, 45.2, and 25.1% of patients), and longer hospital LOS (mean [standard deviation (SD)] of 8.6 [11.4], 5.1 [8.9], and 4.2 [8.0] days) and intensive care unit (ICU) LOS (mean [SD] of 7.8 [8.5], 3.6 [6.2], and 3.6 [5.9] days). For all groups, the presence of a non-SARS-CoV-2 pathogen was associated with increased hospital LOS (mean [SD] days for patients with versus without a non-SARS-CoV-2 pathogen: 13.7 [15.7] vs 7.3 [9.6] days for SARS-CoV-2-positive patients, 8.2 [11.5] vs 4.3 [7.9] days for SARS-CoV-2-negative patients, and 7.1 [11.0] vs 3.9 [7.4] days for SARS-CoV-2-untested patients). CONCLUSIONS: Despite similar rates of non-SARS-CoV-2 pathogens in SARS-CoV-2-positive, -negative, and -untested patients, SARS-CoV-2 was associated with higher rates of hospital-onset infections, greater antimicrobial usage, and extended hospital and ICU LOS. This finding highlights the heavy burden of the COVID-19 pandemic on healthcare systems and suggests possible opportunities for diagnostic and antimicrobial stewardship.

Rapid Spread and Control of Multidrug-Resistant Gram-Negative Bacteria in COVID-19 Patient Care Units.

We describe rapid spread of multidrug-resistant gram-negative bacteria among patients in dedicated coronavirus disease care units in a hospital in Maryland, USA, during May-June 2020. Critical illness, high antibiotic use, double occupancy of single rooms, and modified infection prevention practices were key contributing factors. Surveillance culturing aided in outbreak recognition and control.

Etiology and antimicrobial resistance of secondary bacterial infections in patients hospitalized with COVID-19 in Wuhan, China: a retrospective analysis.

BACKGROUND: A considerable proportion of patients hospitalized with coronavirus disease 2019 (COVID-19) acquired secondary bacterial infections (SBIs). The etiology and antimicrobial resistance of bacteria were reported and used to provide a theoretical basis for appropriate infection therapy. METHODS: This retrospective study reviewed electronic medical records of all the patients hospitalized with COVID-19 in the Wuhan Union Hospital between January 27 and March 17, 2020. According to the inclusion and exclusion criteria, patients who acquired SBIs were enrolled. Demographic, clinical course, etiology, and antimicrobial resistance data of the SBIs were collected. Outcomes were also compared between patients who were classified as severe and critical on admission. RESULTS: Among 1495 patients hospitalized with COVID-19, 102 (6.8%) patients had acquired SBIs, and almost half of them (49.0%, 50/102) died during hospitalization. Compared with severe patients, critical patients had a higher chance of SBIs. Among the 159 strains of bacteria isolated from the SBIs, 136 strains (85.5%) were Gram-negative bacteria. The top three bacteria of SBIs were A. baumannii (35.8%, 57/159), K. pneumoniae (30.8%, 49/159), and S. maltophilia (6.3%, 10/159). The isolation rates of carbapenem-resistant A. baumannii and K. pneumoniae were 91.2 and 75.5%, respectively. Meticillin resistance was present in 100% of Staphylococcus aureus and Coagulase negative staphylococci, and vancomycin resistance was not found. CONCLUSIONS: SBIs may occur in patients hospitalized with COVID-19 and lead to high mortality. The incidence of SBIs was associated with the severity of illness on admission. Gram-negative bacteria, especially A. baumannii and K. pneumoniae, were the main bacteria, and the resistance rates of the major isolated bacteria were generally high. This was a single-center study; thus, our results should be externally examined when applied in other institutions.