Nationwide Outbreak of Candida auris Infections Driven by COVID-19 Hospitalizations, Israel, 2021-2022

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

Multiplex lateral flow immunochromatographic assay is an effective method to detect carbapenemases without risk of OXA-48-like cross reactivity.

BACKGROUND: It is essential to detect carriers of carbapenemase-producing Enterobacterales in order to implement infection control measures. The objectives of this study was to evaluate the NG-Test® CARBA 5 (CARBA 5) assay for detection of five carbapenemases and to assess the cross reactivity of other OXA-type carbapenemases with the OXA-48-like specific antibodies. METHODS: A total of 197 Enterobacterales isolates were tested. To evaluate the cross reactivity, 73 carbapenem-resistant A. baumannii, harboring OXA-type variants, were tested. Polymerase chain reaction (PCR) served as gold standard for carbapenemase identification. RESULTS: Excellent agreement was found between PCR and CARBA 5, for all but one isolate. The single false positive result (a blaSME positive S. marcescens isolate) was incorrectly positive for blaOXA-48 by CARBA 5. No cross reactivity was observed. The sensitivity and specificity were 100.0% and 98.0%, respectively. CONCLUSIONS: The CARBA 5 assay is highly sensitive and specific and is recommended as a tool for the detection of the main carbapenemases of interest in clinical microbiology laboratories.

Colistin Resistance Development Following Colistin-Meropenem Combination Therapy Versus Colistin Monotherapy in Patients With Infections Caused by Carbapenem-Resistant Organisms.

BACKGROUND: We evaluated whether carbapenem-colistin combination therapy reduces the emergence of colistin resistance, compared to colistin monotherapy, when given to patients with infections due to carbapenem-resistant Gram-negative organisms. METHODS: This is a pre-planned analysis of a secondary outcome from a randomized, controlled trial comparing colistin monotherapy with colistin-meropenem combination for the treatment of severe infections caused by carbapenem-resistant, colistin-susceptible Gram-negative bacteria. We evaluated rectal swabs taken on Day 7 or later for the presence of new colistin-resistant (ColR) isolates. We evaluated the emergence of any ColR isolate and the emergence of ColR Enterobacteriaceae (ColR-E). RESULTS: Data were available for 214 patients for the primary analysis; emergent ColR organisms were detected in 22 (10.3%). No difference was observed between patients randomized to treatment with colistin monotherapy (10/106, 9.4%) versus patients randomized to colistin-meropenem combination therapy (12/108, 11.1%; P = .669). ColR-E organisms were detected in 18/249 (7.2%) patients available for analysis. No difference was observed between the 2 treatment arms (colistin monotherapy 6/128 [4.7%] vs combination therapy 12/121 [9.9%]; P = .111). Enterobacteriaceae, as the index isolate, was found to be associated with development of ColR-E (hazard ratio, 3.875; 95% confidence interval, 1.475-10.184; P = .006). CONCLUSIONS: Carbapenem-colistin combination therapy did not reduce the incidence of colistin resistance emergence in patients with infections due to carbapenem-resistant organisms. Further studies are necessary to elucidate the development of colistin resistance and methods for its prevention.

Fourier Transform Infrared Spectroscopy Is a New Option for Outbreak Investigation: a Retrospective Analysis of an Extended-Spectrum-Beta-Lactamase-Producing Klebsiella pneumoniae Outbreak in a Neonatal Intensive Care Unit.

The IR Biotyper is a new automated typing system based on Fourier-transform infrared (FT-IR) spectroscopy that gives results within 4 h. We aimed (i) to use the IR Biotyper to retrospectively analyze an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) in a neonatal intensive care unit and to compare results to BOX-PCR and whole-genome sequencing (WGS) results as the gold standard and (ii) to assess how the cutoff values used to define clusters affect the discriminatory power of the IR Biotyper. The sample consisted of 18 isolates from 14 patients. Specimens were analyzed in the IR Biotyper using the default analysis settings, and spectra were analyzed using OPUS 7.5 software. The software contains a feature that automatically proposes a cutoff value to define clusters; the cutoff value defines up to which distance the spectra are considered to be in the same cluster. Based on FT-IR, the outbreak represented 1 dominant clone, 1 secondary clone, and several unrelated clones. FT-IR results, using the cutoff value generated by the accompanying software after 4 replicates, were concordant with WGS for all but 1 isolate. BOX-PCR was underdiscriminatory compared to the other two methods. Using the cutoff value generated after 12 replicates, the results of FT-IR and WGS were completely concordant. The IR Biotyper can achieve the same typeability and discriminatory power as genome-based methods. However, to attain this high performance requires either previous, strain-dependent knowledge about the optimal technical parameters to be used or validation by a second method.

Performance of Rapid Polymyxin™ NP and Rapid Polymyxin™ Acinetobacter for the detection of polymyxin resistance in carbapenem-resistant Acinetobacter baumannii and Enterobacterales.

BACKGROUND: The global spread of carbapenem-resistant Enterobacterales (CRE) and Acinetobacter baumannii (CRAB) has prompted the reintroduction of colistin as a last-resort treatment. Although the recommended method for colistin susceptibility testing is broth microdilution (BMD), methods that are more rapid and easy to use are needed. OBJECTIVES: To evaluate the performance of two commercial kits for colistin susceptibility testing: Rapid Polymyxin™ NP (RP-NP) for CRE and Rapid Polymyxin™ Acinetobacter (RP-AB) for CRAB. METHODS: A total of 76 CRE and 87 CRAB isolates were collected from hospitalized patients in Europe and Israel. The isolates were subcultured twice on 5% sheep blood in tryptic soy agar. We tested colistin susceptibility using the RP-NP and RP-AB kits and compared the results with those from BMD. RESULTS: Of the CRE isolates, 25% (19/76) were resistant to colistin using BMD. Categorical agreement between RP-NP and BMD was 93.4% (71/76), major errors 1.8% (1/57) and very major errors 21.1% (4/19). Sensitivity was 78.9% and specificity was 98.2%. Of the CRAB isolates, 58.6% (51/87) were resistant to colistin by BMD. Categorical agreement between RP-AB and BMD was 59.8% (52/87), major errors 13.9% (5/36) and very major errors 58.8% (30/51). Sensitivity of RP-AB was 41.2% and specificity was 86.1%. CONCLUSIONS: In many of the tested isolates, weak or inconclusive colour changes in the test wells caused difficulty in interpretation, resulting in an unacceptable rate of very major errors.

Rapid identification of capsulated Acinetobacter baumannii using a density-dependent gradient test.

BACKGROUND: Gram-negative bacterial capsules are associated with production of carbohydrates, frequently resulting in a mucoid phenotype. Infections caused by capsulated or mucoid A. baumannii are associated with increased clinical severity. Therefore, it is clinically and epidemiologically important to identify capsulated A. baumannii. Here, we describe a density-dependent gradient test to distinguish between capsulated and thin/non-capsulated A. baumannii. RESULTS: Thirty-one of 57 A. baumannii isolates displayed a mucoid phenotype. The density-dependent gradient test was comprised of two phases, with silica concentrations of 30% (top phase) and 50% (bottom phase). Twenty-three isolates migrated to the bottom phase, indicating thin or non-capsulated strains, and 34 migrated to the top phase, suggesting strains suspected to be capsulated. There was agreement between the mucoid and the non-mucoid phenotypes and the density-dependent gradient test for all but three isolates. Total carbohydrates extracted from strains suspected to be capsulated were significantly higher. Transmission electron microscopy confirmed the presence of a capsule in the six representative strains suspected to be capsulated. CONCLUSIONS: The density-dependent gradient test can be used to verify capsule presence in mucoid-appearing A. baumannii strains. Identifying capsulated strains can be useful for directing infection control measures to reduce the spread of hypervirulent strains.

Treatment Outcomes of Colistin- and Carbapenem-resistant Acinetobacter baumannii Infections: An Exploratory Subgroup Analysis of a Randomized Clinical Trial.

BACKGROUND: We evaluated the association between mortality and colistin resistance in Acinetobacter baumannii infections and the interaction with antibiotic therapy. METHODS: This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) identified as colistin susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed as CoS with those whose isolates were retrospectively identified as colistin resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality. RESULTS: Data were available for 266 patients (214 CoS and 52 CoR isolates). Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (P = .174). After adjusting for variables associated with mortality, the mortality rate was lower among patients with CoR isolates (odds ratio [OR], 0.285 [95% confidence interval {CI}, .118-.686]). This difference was associated with treatment arm: Mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination therapy compared to colistin monotherapy (OR, 3.065 [95% CI, 1.021-9.202]). CONCLUSIONS: Colistin resistance determined by BMD was associated with lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy. CLINICAL TRIALS REGISTRATION: NCT01732250.

Carbapenem-resistant Acinetobacter baumannii carrier detection: a simple and efficient protocol.

Timely detection of carbapenem-resistant Acinetobacter baumannii (CRAB) carriers is essential to direct infection control measures. In this work, we aimed to develop a practical protocol to detect CRAB from screening samples. To choose a selective medium that detects CRAB with high sensitivity and specificity, 111 A. baumannii clinical isolates were inoculated on three types of agar: mSuperCARBA (SC), CHROMagar Acinetobacter (CaA), and modified CHROMagar Acinetobacter (mCaA) containing 4.5 mg/mL meropenem. SC was non-selective, CaA was the most sensitive (100%), but only moderately specific (72%), and mCaA was highly specific (97%) and sensitive (98%). Confirmation of the carbapenem-resistant phenotype using PCR-based detection of blaOXA-23, blaOXA-24, and blaOXA-58 genes was specific but not sensitive, detecting only 58% of CRAB isolates. Identification of A. baumannii using either gyrB or blaOXA-51 PCR was excellent. Next, we used the same methodology in routine screening for CRAB carriage. mCaA had the best yield, with high sensitivity but moderate specificity to differentiate between CRAB and other carbapenem-resistant organisms. Skin sampling using sponges and 6 hour enrichment was highly sensitive (98%), while other body sites had poor sensitivity (27%- 41%). Shorter incubation had slightly lower yield, and longer incubation did not improve the detection. Performing PCR for blaOXA-51 and gyrB on colonies growing on modified mCaA differentiated between CRAB and other species with high accuracy (98% and 99%, respectively). Based on our results, we present a procedure for easy and reliable detection of CRAB carriage using skin sampling, short enrichment, selection on mCaA, and PCR-based identification. IMPORTANCE: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a substantial cause of nosocomial infections, classified among the most significant multidrug-resistant pathogens by the World Health Organization and by the US Centers for Disease Control. Limiting the spread of CRAB is an important goal of infection control, but laboratory methods for identification of CRAB carriers are not standardized. In this work, we compared different selective agar plates, tested the efficiency of A. baumannii identification by PCR for species-specific genes, and used PCR-based detection of common resistance genes to confirm the carbapenem-resistant phenotype. During a prospective study, we also determined the optimal sample enrichment time. Based on our results, we propose a simple and efficient protocol for the detection of CRAB carriage using skin sampling, short enrichment, selection on appropriate agar plates, and PCR-based identification, resulting in a turn-around time of 24 hours.

Integration of individual preclinical and clinical anti-infective PKPD data to predict clinical study outcomes.

The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination therapy in carbapenem-resistant Gram-negative infections. The aim of this reverse translational study was to integrate all individual preclinical and clinical pharmacokinetic-pharmacodynamic (PKPD) data from the AIDA trial in a pharmacometric framework to explore whether individualized predictions of bacterial burden were associated with the trial outcomes. The compiled dataset included for each of the 207 patients was (i) information on the infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, and fitness in a murine model), (ii) colistin plasma concentrations and colistin and meropenem dosing history, and (iii) disease scores and demographics. The individual information was integrated into PKPD models, and the predicted change in bacterial count at 24 h for each patient, as well as patient characteristics, was correlated with clinical outcomes using logistic regression. The in vivo fitness was the most important factor for change in bacterial count. A model-predicted growth at 24 h of ≥2-log10 (164/207) correlated positively with clinical failure (adjusted odds ratio, aOR = 2.01). The aOR for one unit increase of other significant predictors were 1.24 for SOFA score, 1.19 for Charlson comorbidity index, and 1.01 for age. This study exemplifies how preclinical and clinical anti-infective PKPD data can be integrated through pharmacodynamic modeling and identify patient- and pathogen-specific factors related to clinical outcomes - an approach that may improve understanding of study outcomes.

Comparing the efficacy of antimicrobial pocket-irrigation protocols in an in vivo breast implant infection model.

BACKGROUND: Breast implant infection and biofilm formation are major concerns in reconstructive and esthetic breast surgery, with significant medical and economic consequences. Staphylococcus is the common pathogen, with rapidly increasing rates of methicillin-resistant Staphylococcus aureus (MRSA). There is no consensus on prevention practices. This study compares the effect of several pocket irrigation and antibiotic prophylaxis regimens on implant colonization and biofilm formation in an established rat model of MRSA-infected silicone breast implants. METHODS: Silicone discs were inserted in a sub-pectoral pocket in 57 rats (114 implants). Implant infection was induced by injection of free planktonic MRSA into the surgical pocket. Rats were allocated to study groups treated by different antimicrobial protocols: pocket irrigation with vancomycin, povidone-iodine, or saline. Each group was divided into subgroups treated with or without additional peri-operative systemic vancomycin. Implant colonization or overt infection was assessed at post-operative day 14 both clinically and by cultures. RESULTS: Pocket irrigation with vancomycin prevented contamination in 87% of implants. Irrigation and systemic vancomycin prevented contamination in 100% of implants with no difference between a single preoperative dose and a 48-h regimen. Systemic vancomycin alone or irrigation with povidone-iodine alone resulted in 100% contamination rates. CONCLUSIONS: In this in vivo model, combination of systemic vancomycin with vancomycin pocket irrigation was the most effective regimen, preventing contamination in 100% of implants. Continuation of post-operative antibiotic treatment showed no added advantage.

Carriage of vancomycin-resistant Enterococcus faecium in infants following an outbreak in the neonatal intensive care unit: time to clearance of carriage and use of molecular methods to detect colonization.

Among 46 infants colonized with vancomycin-resistant Enterococcus faecium during an outbreak in a neonatal intensive care unit, the estimated time until half had achieved clearance was 217 days. All 40 infants who completed follow-up cleared carriage by 1 year. No predictors of prolonged carriage (> 6 months) were identified.

Prevalence and Clinical Consequences of Colistin Heteroresistance and Evolution into Full Resistance in Carbapenem-Resistant Acinetobacter baumannii.

Colistin heteroresistance (HR) refers to a bacterial population comprised of several subpopulations with different levels of resistance to colistin. In this study, we discuss the classic form of HR, in which a resistant subpopulation exists within a predominantly susceptible population. We investigated the prevalence of colistin HR and its evolution into full resistance among 173 clinical carbapenem-resistant Acinetobacter baumannii isolates and examined the effect of HR on clinical outcomes. To determine HR, we performed population analysis profiling. Our results showed a high prevalence of HR (67.1%). To examine evolution of HR strains into full resistance, the HR strains were grown in colistin-containing broth, transferred onto colistin-containing plates, and colonies on these plates were transferred into colistin-free broth. Many of the HR strains (80.2%) evolved into full resistance, 17.2% reverted to HR, and 2.6% were borderline. We used logistic regression to compare 14-day clinical failure and 14-day mortality between patients infected by HR versus susceptible non-HR carbapenem-resistant A. baumannii. In the subgroup of patients with bacteremia, HR was significantly associated with 14-day mortality. IMPORTANCE To our knowledge, this is the first large-scale study to report on HR in Gram-negative bacteria. We described the prevalence of colistin HR in a large sample of carbapenem-resistant A. baumannii isolates, the evolution of many colistin HR isolates to a resistant phenotype following colistin exposure and withdrawal, and the clinical consequences of colistin HR. We found a high prevalence of HR among clinical carbapenem-resistant A. baumannii isolates; most evolved into a resistant phenotype following colistin exposure and withdrawal. In patients treated with colistin, evolution of HR A. baumannii into full resistance could lead to higher rates of treatment failure and contribute to the reservoir of colistin-resistant pathogens in health care settings.

Understanding the antibacterial mechanism of CuO nanoparticles: revealing the route of induced oxidative stress.

To date, there is still a lack of definite knowledge regarding the interaction of CuO nanoparticles with bacteria and the possible permeation of the nanoparticles into bacterial cells. This study was aimed at shedding light on the size-dependent (from the microscale down to the small nanoscale) antibacterial activity of CuO. The potent antibacterial activity of CuO nanoparticles was found to be due to ROS-generation by the nanoparticles attached to the bacterial cells, which in turn provoked an enhancement of the intracellular oxidative stress. This paradigm was confirmed by several assays such as lipid peroxidation and reporter strains of oxidative stress. Furthermore, electron microscopy indicated that the small nanoparticles of CuO penetrated the cells. Collectively, the results reported herein may reconcile conflicting concepts in the literature concerning the antibacterial mechanism of CuO nanoparticles, as well as highlight the potential for developing sustainable CuO nanoparticles-based devices for inhibiting bacterial infections.

Sonochemical coatings of ZnO and CuO nanoparticles inhibit Streptococcus mutans biofilm formation on teeth model.

Antibiotic resistance has prompted the search for new agents that can inhibit bacterial growth. We recently reported on the antibiofilm activities of nanosized ZnO and CuO nanoparticles (NPs) synthesized by using sonochemical irradiation. In this study, we examined the antibacterial activity of ZnO and CuO NPs in a powder form and also examined the antibiofilm behavior of teeth surfaces that were coated with ZnO and CuO NPs using sonochemistry. Free ZnO and CuO NPs inhibited biofilm formation of Streptococcus mutans . Furthermore, by using the sonochemical procedure, we were able to coat teeth surfaces that inhibited bacterial colonization.

Improved antibacterial and antibiofilm activity of magnesium fluoride nanoparticles obtained by water-based ultrasound chemistry.

Antibiotic resistance has prompted the search for new agents that can inhibit bacterial growth. We recently reported on the antimicrobial and antibiofilm activities of nanosized magnesium fluoride (MgF(2)) nanoparticles (NPs) synthesized in ionic liquid using microwave chemistry. In this article, we describe a novel water-based synthesis of MgF(2) NPs using sonochemistry. The sonochemical irradiation of an aqueous solution of [Mg(OAc)(2)⋅(H(2)O)(4)] containing acidic HF as the fluorine ion source afforded crystalline well-shaped spherical MgF(2) NPs that showed much improved antibacterial properties against two common bacterial pathogens (Escherichia coli and Staphylococcus aureus). We were also able to demonstrate that the antimicrobial activity was dependent on the size of the NPs. In addition, using the described sonochemical process, we coated glass surfaces and demonstrated inhibition of bacterial colonization for 7 days. Finally, the antimicrobial activity of MgF(2) NPs against established biofilms was also examined. Taken together our results highlight the potential to further develop the concept of utilizing these metal fluoride NPs as novel antimicrobial and antibiofilm agents. FROM THE CLINICAL EDITOR: In this article, the authors describe a novel aqueous synthesis of magnesium fluoride NPs using sonochemistry. These nanoparticles have improved antibacterial and antibiofilm activity compared to their counterparts with traditional synthesis methods.

Pandora's box in the dental clinic.

BACKGROUND: In June 2018, the Ministry of Health received notification from 2 hospitals about 2 patients who presented with overwhelming Enterobacter kobei sepsis that developed within 24 hours after a dental procedure. We describe the investigation of this outbreak. METHODS: The epidemiologic investigation included site visits in 2 dental clinics and interviews with all involved healthcare workers. Chart reviews were conducted for case and control subjects. Samples were taken from medications and antiseptics, environmental surfaces, dental water systems, and from the involved healthcare professionals. Isolate similarity was assessed using repetitive element sequence-based polymerase chain reaction (REP-PCR). RESULTS: The 2 procedures were conducted in different dental clinics by different surgeons and dental technicians. A single anesthesiologist administered the systemic anesthetic in both cases. Cultures from medications, fluids and healthcare workers' hands were negative, but E. kobei was detected from the anesthesiologist's portable medication cart. The 2 human isolates and the environmental isolate shared the same REP-PCR fingerprinting profile. None of the 21 patients treated by the anesthesiologist in a general hospital during the same period, using the hospital's medications, developed infection following surgery. CONCLUSIONS: An outbreak of post-dental-procedure sepsis was linked to a contaminated medication cart, emphasizing the importance of medication storage standards and strict aseptic technique when preparing intravenous drugs during anesthesia. Immediate reporting of sepsis following these outpatient procedures enabled early identification and termination of the outbreak.

High rate of bacterial respiratory tract co-infections upon admission amongst moderate to severe COVID-19 patients.

BACKGROUND: The role of bacterial and viral co-infection in the current COVID-19 pandemic remains elusive. The aim of this study was to describe the rates and features of co-infection on admission of COVID-19 patients, based on molecular and routine laboratory methods. METHODS: A retrospective study of COVID-19 and non-COVID-19 patients undergoing Biofire®, FilmArray® Pneumonia Panel, bioMérieux, and routine cultures during the first 3 days from admission, between June 2019 and March 2021. RESULTS: FilmArray tests were performed in 115 COVID-19 and in 61 non-COVID-19 patients. Most (>99%) COVID-19 patients had moderate-critical illness, 37% required mechanical ventilation. Sputa and endotracheal aspirates were the main samples analyzed. Positive FilmArray tests were found in 60% (70/116) of the tests amongst COVID-19 patients and 62.5% (40/64) amongst non-COVID-19 patients. All 70 cases were positive for bacterial targets, while one concomitant virus (Rhinovirus/Enterovirus) and one Legionella spp. were detected. The most common bacterial targets were Haemophilus influenzae (36%), Staphylococcus aureus (23%), Streptococcus pneumoniae (10%) and Enterobacter cloacae (10%). Correlation between FilmArray and cultures was found in 81% and 44% of negative and positive FA tests, respectively. Positive FilmArray results typically (81%) triggered the administration of antibiotic therapy and negative results resulted in antimicrobials to be withheld in 56% of cases and stopped in 8%. Bacterial cultures of COVID-19 patients were positive in 30/88 (34%) of cases. CONCLUSIONS: Bacterial co-infection is common amongst moderate-critical COVID-19 patients on admission while viral and atypical bacteria were exceedingly rare. Positive FilmArray results could trigger potentially unnecessary antibiotic treatment.KEY POINTWe found high rates of on-admission bacterial co-infection amongst hospitalized moderate to severe COVID-19 patients. Molecular tests (Biofire, FilmArray) and routine microbiological tests revealed 60% and 34% bacterial co-infection, respectively, while viral and fungal co-infections were rare.

In vivo fitness of carbapenem-resistant Acinetobacter baumannii strains in murine infection is associated with treatment failure in human infections.

OBJECTIVES: Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections. METHODS: Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 105 CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes. RESULTS: The sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04-2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03-2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95-2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09-3.25). CONCLUSIONS: In vivo CRAB fitness was associated with clinical failure in patients with CRAB infection.

An outbreak of carbapenem-resistant Acinetobacter baumannii in a COVID-19 dedicated hospital.

We describe an outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) in a COVID-19 dedicated hospital. The suspected mechanism of transfer was an environmental source that persisted despite evacuation and terminal cleaning of the entire hospital, and transmitted through healthcare workers' hands or equipment. This outbreak demonstrates that practices to prevent the spread of multidrug-resistant organisms must not be neglected during the COVID-19 pandemic.

Occurrence of BNT162b2 Vaccine Adverse Reactions Is Associated with Enhanced SARS-CoV-2 IgG Antibody Response.

Promoting SARS-CoV-2 vaccination has been a global mission since the first vaccines were approved for emergency use. Alongside the excitement following the possibility of eradicating SARS-CoV-2 and ending the COVID-19 pandemic, there has been ample vaccine hesitancy, some due to the abundant reporting of adverse reactions. We report here that the occurrence of BNT162b2 vaccine adverse reactions is associated with enhanced antibody response. We found a statistically significant correlation between having an adverse reaction, whether local or systemic, and higher antibody levels. No sex difference was observed in antibody levels. However, as was recently reported, the antibody response was found to be lower among older vaccinees. The demonstration of a clear correlation between adverse reactions and antibody levels may help reduce vaccination hesitancy by reassuring that the presence of such reactions is an indication of a well-functioning immune system.