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1.
Sci Rep ; 12(1): 8763, 2022 05 24.
Article in English | MEDLINE | ID: covidwho-1873545

ABSTRACT

Cefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore antibiotic approved to treat complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-acquired pneumonia (HAP/VAP). Previous work determined that albumin-rich human fluids increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems. This latter effect may contribute to the need for higher concentrations of CFDC to inhibit growth. The presence of human urine (HU), which contains low albumin concentrations, did not modify MIC values of two carbapenem-resistant A. baumannii. Levels of resistance to CFDC were not modified by HU in strain AMA40 but were reduced in strain AB5075. Expanding the studies to other carbapenem-resistant A. baumannii isolates showed that the presence of HU resulted in unmodified or reduced MIC of CDFC values. The expression of piuA, pirA, bauA, and bfnH determined by qRT-PCR was enhanced in A. baumannii AMA40 and AB5075 by the presence of HU in the culture medium. All four tested genes code for functions related to recognition and transport of ferric-siderophore complexes. The effect of HU on expression of pbp1, pbp3, blaOXA-51-like, blaADC, and blaNDM-1, genes associated with resistance to ß-lactams, as well as genes coding for efflux pumps and porins was variable, showing dependence with the strain analyzed. We conclude that the lack of significant concentrations of albumin and free iron in HU makes this fluid behave differently from others we tested. Unlike other albumin rich fluids, the presence of HU does not impact the antibacterial activity of CFDC when tested against A. baumannii.


Subject(s)
Acinetobacter baumannii , Albumins/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenems/pharmacology , Cephalosporins , Humans , Iron/pharmacology , Microbial Sensitivity Tests , Siderophores , beta-Lactamases/genetics
2.
Am J Infect Control ; 50(5): 477-481, 2022 05.
Article in English | MEDLINE | ID: covidwho-1838507

ABSTRACT

BACKGROUND: A carbapenem-resistant Acinetobacter baumannii outbreak in the COVID intensive care unit of a community hospital was contained using multidrug resistant organism guidelines. The purpose of this study is to report on an outbreak investigation and containment strategy that was used, and to discuss prevention strategy. METHODS: A multidisciplinary approach contained the spread of infection. Strategies implemented included consultation with experts, screening, and reversal of personal protective equipment conservation. Ensuring infection control best practices are maintained remain important efforts to reduce the spread of multidrug resistant organisms. RESULTS: Five patients with carbapenem-resistant Acinetobacter baumannii were identified from routine clinical cultures within one week and one patient was identified from active surveillance cultures. DISCUSSION: Personal protective equipment conservation, strategies to prevent health care personnel exposure, and patient surge staffing protocols may have increased the likelihood of multidrug resistant organism transmission. Environmental and behavioral infection control regulations with effective administrative guidance, active surveillance cultures, and antimicrobial stewardship are critical to prevent future outbreaks. CONCLUSIONS: After outbreak containment strategies were implemented, no additional patients were identified with carbapenem-resistant Acinetobacter baumannii. Conventional infection prevention and control strategies were re-instituted. A multidisciplinary approach with continued focus on hand hygiene, environmental cleaning, and correct use of personal protective equipment needs to be put in place to successfully contain and prevent the spread of carbapenem resistant infections.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , COVID-19 , Cross Infection , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , Carbapenems/pharmacology , Carbapenems/therapeutic use , Cross Infection/epidemiology , Cross Infection/prevention & control , Disease Outbreaks/prevention & control , Drug Resistance, Multiple, Bacterial , Humans , Intensive Care Units
3.
Drugs ; 82(5): 533-557, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1827389

ABSTRACT

Sulopenem (formerly known as CP-70,429, and CP-65,207 when a component of a racemic mixture with its R isomer) is an intravenous and oral penem that possesses in vitro activity against fluoroquinolone-resistant, extended spectrum ß-lactamases (ESBL)-producing, multidrug-resistant (MDR) Enterobacterales. Sulopenem is being developed to treat patients with uncomplicated and complicated urinary tract infections (UTIs) as well as intra-abdominal infections. This review will focus mainly on its use in UTIs. The chemical structure of sulopenem shares properties of penicillins, cephalosporins, and carbapenems. Sulopenem is available as an oral prodrug formulation, sulopenem etzadroxil, which is hydrolyzed by intestinal esterases, resulting in active sulopenem. In early studies, the S isomer of CP-65,207, later developed as sulopenem, demonstrated greater absorption, higher drug concentrations in the urine, and increased stability against the renal enzyme dehydropeptidase-1 compared with the R isomer, which set the stage for its further development as a UTI antimicrobial. Sulopenem is active against both Gram-negative and Gram-positive microorganisms. Sulopenem's ß-lactam ring alkylates the serine residues of penicillin-binding protein (PBP), which inhibits peptidoglycan cross-linking. Due to its ionization and low molecular weight, sulopenem passes through outer membrane proteins to reach PBPs of Gram-negative bacteria. While sulopenem activity is unaffected by many ß-lactamases, resistance arises from alterations in PBPs (e.g., methicillin-resistant Staphylococcus aureus [MRSA]), expression of carbapenemases (e.g., carbapenemase-producing Enterobacterales and in Stenotrophomonas maltophilia), reduction in the expression of outer membrane proteins (e.g., some Klebsiella spp.), and the presence of efflux pumps (e.g., MexAB-OprM in Pseudomonas aeruginosa), or a combination of these mechanisms. In vitro studies have reported that sulopenem demonstrates greater activity than meropenem and ertapenem against Enterococcus faecalis, Listeria monocytogenes, methicillin-susceptible S. aureus (MSSA), and Staphylococcus epidermidis, as well as similar activity to carbapenems against Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes. With some exceptions, sulopenem activity against Gram-negative aerobes was less than ertapenem and meropenem but greater than imipenem. Sulopenem activity against Escherichia coli carrying ESBL, CTX-M, or Amp-C enzymes, or demonstrating MDR phenotypes, as well as against ESBL-producing Klebsiella pneumoniae, was nearly identical to ertapenem and meropenem and greater than imipenem. Sulopenem exhibited identical or slightly greater activity than imipenem against many Gram-positive and Gram-negative anaerobes, including Bacteroides fragilis. The pharmacokinetics of intravenous sulopenem appear similar to carbapenems such as imipenem-cilastatin, meropenem, and doripenem. In healthy subjects, reported volumes of distribution (Vd) ranged from 15.8 to 27.6 L, total drug clearances (CLT) of 18.9-24.9 L/h, protein binding of approximately 10%, and elimination half-lives (t½) of 0.88-1.03 h. The estimated renal clearance (CLR) of sulopenem is 8.0-10.6 L/h, with 35.5% ± 6.7% of a 1000 mg dose recovered unchanged in the urine. An ester prodrug, sulopenem etzadroxil, has been developed for oral administration. Initial investigations reported a variable oral bioavailability of 20-34% under fasted conditions, however subsequent work showed that bioavailability is significantly improved by administering sulopenem with food to increase its oral absorption or with probenecid to reduce its renal tubular secretion. Food consumption increases the area under the curve (AUC) of oral sulopenem (500 mg twice daily) by 23.6% when administered alone and 62% when administered with 500 mg of probenecid. Like carbapenems, sulopenem demonstrates bactericidal activity that is associated with the percentage of time that free concentrations exceed the MIC (%f T > MIC). In animal models, bacteriostasis was associated with %f T > MICs ranging from 8.6 to 17%, whereas 2-log10 kill was seen at values ranging from 12 to 28%. No pharmacodynamic targets have been documented for suppression of resistance. Sulopenem concentrations in urine are variable, ranging from 21.8 to 420.0 mg/L (median 84.4 mg/L) in fasted subjects and 28.8 to 609.0 mg/L (median 87.3 mg/L) in those who were fed. Sulopenem has been compared with carbapenems and cephalosporins in guinea pig and murine systemic and lung infection animal models. Studied pathogens included Acinetobacter calcoaceticus, B. fragilis, Citrobacter freundii, Enterobacter cloacae, E. coli, K. pneumoniae, Proteus vulgaris, and Serratia marcescens. These studies reported that overall, sulopenem was non-inferior to carbapenems but appeared to be superior to cephalosporins. A phase III clinical trial (SURE-1) reported that sulopenem was not non-inferior to ciprofloxacin in women infected with fluoroquinolone-susceptible pathogens, due to a higher rate of asymptomatic bacteriuria in sulopenem-treated patients at the test-of-cure visit. However, the researchers reported superiority of sulopenem etzadroxil/probenecid over ciprofloxacin for the treatment of uncomplicated UTIs in women infected with fluoroquinolone/non-susceptible pathogens, and non-inferiority in all patients with a positive urine culture. A phase III clinical trial (SURE-2) compared intravenous sulopenem followed by oral sulopenem etzadroxil/probenecid with ertapenem in the treatment of complicated UTIs. No difference in overall success was noted at the end of therapy. However, intravenous sulopenem followed by oral sulopenem etzadroxil was not non-inferior to ertapenem followed by oral stepdown therapy in overall success at test-of-cure due to a higher rate of asymptomatic bacteriuria in the sulopenem arm. After a meeting with the US FDA, Iterum stated that they are currently evaluating the optimal design for an additional phase III uncomplicated UTI study to be conducted prior to the potential resubmission of the New Drug Application (NDA). It is unclear at this time whether Iterum intends to apply for EMA or Japanese regulatory approval. The safety and tolerability of sulopenem has been reported in various phase I pharmacokinetic studies and phase III clinical trials. Sulopenem (intravenous and oral) appears to be well tolerated in healthy subjects, with and without the coadministration of probenecid, with few serious drug-related treatment-emergent adverse events (TEAEs) reported to date. Reported TEAEs affecting ≥1% of patients were (from most to least common) diarrhea, nausea, headache, vomiting and dizziness. Discontinuation rates were low and were not different than comparator agents. Sulopenem administered orally and/or intravenously represents a potentially well tolerated and effective option for treating uncomplicated and complicated UTIs, especially in patients with documented or highly suspected antimicrobial pathogens to commonly used agents (e.g. fluoroquinolone-resistant E. coli), and in patients with documented microbiological or clinical failure or patients who demonstrate intolerance/adverse effects to first-line agents. This agent will likely be used orally in the outpatient setting, and intravenously followed by oral stepdown in the hospital setting. Sulopenem also allows for oral stepdown therapy in the hospital setting from intravenous non-sulopenem therapy. More clinical data are required to fully assess the clinical efficacy and safety of sulopenem, especially in patients with complicated UTIs caused by resistant pathogens such as ESBL-producing, Amp-C, MDR E. coli. Antimicrobial stewardship programs will need to create guidelines for when this oral and intravenous penem should be used.


Subject(s)
Bacteriuria , Methicillin-Resistant Staphylococcus aureus , Prodrugs , Urinary Tract Infections , Adenosine Monophosphate/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteriuria/chemically induced , Bacteriuria/drug therapy , Carbapenems/pharmacology , Cephalosporins/pharmacology , Ciprofloxacin/pharmacology , Ertapenem , Escherichia coli , Female , Fluoroquinolones/pharmacology , Gram-Negative Bacteria , Guinea Pigs , Humans , Imipenem/pharmacology , Lactams , Male , Membrane Proteins/pharmacology , Meropenem/pharmacology , Mice , Probenecid/pharmacology , Prodrugs/pharmacology , Staphylococcus aureus , Urinary Tract Infections/drug therapy , beta-Lactamases/pharmacology
4.
J Antimicrob Chemother ; 77(3): 625-632, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1713678

ABSTRACT

OBJECTIVES: Tigecycline is a last-resort antibiotic used to treat lethal infections caused by carbapenem-resistant Enterobacterales; however, plasmid-borne tigecycline resistance tmexCD-toprJ gene clusters can confer tigecycline resistance. The aim of the study was to identify novel subtypes and the spread of tmexCD-toprJ. METHODS: Five non-duplicate isolates of different species, carrying tmexCD-toprJ gene clusters or novel subtypes, were isolated from patients across China between November 2018 and June 2019. WGS was performed using Illumina and Nanopore platforms. A phylogenetic tree was constructed using a dataset of 77 sequences carrying the tmexCD-toprJ gene clusters, 72 of which were downloaded from NCBI with a blastn identity cut-off of 95%. RESULTS: We detected six different transfer units and two novel subtypes (tmexC1D1.2-toprJ1 and tmexC2D2.2-toprJ2) of the tmexCD-toprJ gene clusters. Among the six transfer units, three were mediated by IS26, while the rest were presumably mediated by Tn5393, hypothetical integrases (xerD-hp clusters-umuC-integrases-tnfxB2-tmexC2D2-toprJ2-umuC) and hypothetical units (hp-hp-hp-tnfxB2-tmexC2D2.2-toprJ2-ΔTn5393-Tn6292). Moreover, two tmexCD-toprJ-like gene clusters co-located on the same plasmid with blaNDM in five isolates. Phylogenetic analysis revealed that tmexCD-toprJ gene clusters may have originated in Pseudomonas spp., being mainly distributed in Pseudomonas spp. and Klebsiella spp. (64/77). Most tmexCD-toprJ gene clusters in Enterobacterales were located on plasmids, indicating that the gene clusters have a high inter-species transfer risk after transfer to Enterobacterales. CONCLUSIONS: In summary, to the best of our knowledge, this is the first report of tmexCD-toprJ gene clusters being isolated from Enterobacter cloacae and Klebsiella oxytoca, revealing that these multiple transfer units should be further studied because of their clinical significance.


Subject(s)
Enterobacter cloacae , Klebsiella oxytoca , Carbapenems/pharmacology , Enterobacter cloacae/genetics , Humans , Klebsiella oxytoca/genetics , Microbial Sensitivity Tests , Multigene Family , Phylogeny , beta-Lactamases/genetics
5.
Microbiol Spectr ; 10(1): e0108021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1673361

ABSTRACT

The spread of carbapenem-resistant Pseudomonas aeruginosa and carbapenemase-producing Enterobacterales (CPE) has dramatically impacted morbidity and mortality. COVID-19 pandemic has favored the selection of these microorganisms because of the excessive and prolonged use of broad-spectrum antibiotics and the outbreaks related to patient transfer between hospitals and inadequate personal protective equipment. Therefore, early CPE detection is considered essential for their control. We aimed to compare conventional phenotypic synergy tests and two lateral flow immunoassays for detecting carbapenemases in Enterobacterales and P. aeruginosa. We analyzed 100 carbapenem-resistant Gram-negative bacilli isolates, 80 Enterobacterales, and 20 P. aeruginosa (86 isolates producing KPC, NDM, OXA-48, IMP, and VIM carbapenemases and 14 non-carbapenemase-producing isolates). We performed a modified Hodge test, boronic acid and ethylenediaminetetraacetic acid (EDTA) synergy tests, and two lateral flow immunoassays: RESIST-4 O.K.N.V. (Coris Bioconcept) and NG Test Carba 5 (NG Biotech). In total, 76 KPC, seven VIM, one NDM, one OXA-48, and one isolate coproducing KPC + NDM enzymes were included. The concordance of different methods estimated by the Kappa index was 0.432 (standard error: 0.117), thus showing a high variability with the synergy tests with boronic acid and EDTA and reporting 16 false negatives that were detected by the two immunochromatographic methods. Co-production was only detected using immunoassays. Conventional phenotypic synergy tests with boronic acid and EDTA for detecting carbapenemases are suboptimal, and their routine use should be reconsidered. These tests depend on the degree of enzyme expression and the distance between disks. Lateral flow immunoassay tests are a rapid and cost-effective tool to detect and differentiate carbapenemases, improving clinical outcomes through targeted therapy and promoting infection prevention measures. IMPORTANCE Infections due to multidrug-resistant pathogens are a growing problem worldwide. The production of carbapenemases in Pseudomonas aeruginosa and Enterobacterales cause a high impact on the mortality of infected patients. Therefore, it is of great importance to have methods that allow the early detection of these multi-resistant microorganisms, achieving the confirmation of the type of carbapenemase present, with high sensitivity and specificity, with the aim of improving epidemiological control, dissemination, the clinical course to through targeted antibiotic therapy and promoting infection control in hospitals.


Subject(s)
Gammaproteobacteria/enzymology , Immunoassay/methods , Pseudomonas aeruginosa/enzymology , Carbapenems/metabolism , Carbapenems/pharmacology , Carbon-Nitrogen Ligases/metabolism , Drug Resistance , Immunoassay/standards , Phenotype , Pseudomonas aeruginosa/drug effects
6.
Antimicrob Resist Infect Control ; 11(1): 12, 2022 01 21.
Article in English | MEDLINE | ID: covidwho-1643184

ABSTRACT

BACKGROUND: Despite the adoption of strict infection prevention and control measures, many hospitals have reported outbreaks of multidrug-resistant organisms (MDRO) during the Coronavirus 2019 (COVID-19) pandemic. Following an outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) in our institution, we sought to systematically analyse characteristics of MDRO outbreaks in times of COVID-19, focussing on contributing factors and specific challenges in controlling these outbreaks. METHODS: We describe results of our own CRAB outbreak investigation and performed a systematic literature review for MDRO (including Candida auris) outbreaks which occurred during the COVID-19 pandemic (between December 2019 and March 2021). Search terms were related to pathogens/resistance mechanisms AND COVID-19. We summarized outbreak characteristics in a narrative synthesis and contrasted contributing factors with implemented control measures. RESULTS: The CRAB outbreak occurred in our intensive care units between September and December 2020 and comprised 10 patients (thereof seven with COVID-19) within two distinct genetic clusters (both ST2 carrying OXA-23). Both clusters presumably originated from COVID-19 patients transferred from the Balkans. Including our outbreak, we identified 17 reports, mostly caused by Candida auris (n = 6) or CRAB (n = 5), with an overall patient mortality of 35% (68/193). All outbreaks involved intensive care settings. Non-adherence to personal protective equipment (PPE) or hand hygiene (n = 11), PPE shortage (n = 8) and high antibiotic use (n = 8) were most commonly reported as contributing factors, followed by environmental contamination (n = 7), prolonged critical illness (n = 7) and lack of trained HCW (n = 7). Implemented measures mainly focussed on PPE/hand hygiene audits (n = 9), environmental cleaning/disinfection (n = 9) and enhanced patient screening (n = 8). Comparing potentially modifiable risk factors and control measures, we found the largest discrepancies in the areas of PPE shortage (risk factor in 8 studies, addressed in 2 studies) and patient overcrowding (risk factor in 5 studies, addressed in 0 studies). CONCLUSIONS: Reported MDRO outbreaks during the COVID-19 pandemic were most often caused by CRAB (including our outbreak) and C. auris. Inadequate PPE/hand hygiene adherence, PPE shortage, and high antibiotic use were the most commonly reported potentially modifiable factors contributing to the outbreaks. These findings should be considered for the prevention of MDRO outbreaks during future COVID-19 waves.


Subject(s)
Acinetobacter Infections/prevention & control , Acinetobacter baumannii , COVID-19/complications , COVID-19/epidemiology , Candidiasis/prevention & control , Pandemics , SARS-CoV-2 , Acinetobacter Infections/complications , Acinetobacter baumannii/drug effects , Aged , Candidiasis/complications , Carbapenems/pharmacology , Cross Infection/prevention & control , Disease Outbreaks/prevention & control , Drug Resistance, Multiple, Bacterial , Female , Humans , Infection Control/methods , Male , Middle Aged , Retrospective Studies , Switzerland/epidemiology
7.
Int J Mol Sci ; 22(22)2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1534089

ABSTRACT

Carbapenem-resistant A. baumannii (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Drug Resistance, Bacterial/genetics , Peptides/pharmacology , Acinetobacter Infections/genetics , Acinetobacter Infections/microbiology , Acinetobacter baumannii/pathogenicity , Anti-Infective Agents, Local/pharmacology , Biofilms/drug effects , Carbapenems/adverse effects , Carbapenems/pharmacology , Humans , Microbial Sensitivity Tests
8.
BMC Infect Dis ; 21(1): 927, 2021 Sep 08.
Article in English | MEDLINE | ID: covidwho-1403227

ABSTRACT

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is among the most concerning cause of healthcare-associated infections (HAI) due to its high level of antibiotic resistance and high mortality. In the era of the COVID-19 pandemic, the key priority of infection control committees is to contain the dissemination of antibiotic resistant Gram-negative bacteria. Here, we aimed to timely recognize the emergence of CRAB in COVID-19 cases admitted to the wards of a tertiary referral hospital and to identify the genetic relatedness of the isolates. METHODS: From 30 March to 30 May 2020, a total of 242 clinical samples from COVID-19 cases were screened for CRAB isolates using standard microbiologic and antibiotic susceptibility tests. The PCRs targeting oxa23, oxa24, oxa58, blaTEM and blaNDM-1 genes were performed. Two multiplex PCRs for identifying the global clones (GC) of A. baumannii were also performed. The sequence type of CRABs was determined using Institut Pasteur (IP) multilocus sequence typing (MLST) scheme. RESULTS: Eighteen CRAB isolates were recovered from COVID-19 patients with the mean age of 63.94 ± 13.8 years. All but 4 COVID-19 patients co-infected with CRAB were suffering from an underlying disease. Death was recorded as the outcome in ICUs for 9 (50%) COVID-19 patients co-infected with CRAB. The CRAB isolates belong to GC2 and ST2IP and carried the oxa23 carbapenem resistance gene. CONCLUSION: This study demonstrated the co-infection of CRAB isolates and SARS-CoV-2 in the patients admitted to different ICUs at a referral hospital in Tehran. The CRAB isolates were found to belong to ST2IP, share the oxa23 gene and to have caused several outbreaks in the wards admitting COVID-19 patients.


Subject(s)
Acinetobacter Infections , COVID-19 , Coinfection , Acinetobacter Infections/epidemiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Aged , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , COVID-19/epidemiology , COVID-19/microbiology , Carbapenems/pharmacology , Coinfection/epidemiology , Humans , Iran/epidemiology , Microbial Sensitivity Tests , Middle Aged , Multilocus Sequence Typing , Pandemics , Tertiary Care Centers , beta-Lactamases/genetics
9.
Infect Control Hosp Epidemiol ; 43(4): 461-466, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1349624

ABSTRACT

OBJECTIVE: To assess the incidence of colonization and infection with carbapenemase-producing Enterobacteriaceae (CPE) and carbapenem-resistant Acinetobacter baumannii (CR-Ab) in the ICUs of our city hospitals before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a multicenter, before-and-after, cross-sectional study to compare the rates of colonization and infection with CPE and/or CR-Ab in 2 study periods, period 1 (January-April 2019) and period 2 (January-April 2020). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of weekly colonization and infection rates for each period were compared for the 2 study periods using Poisson regression. Weekly trends in the incidence of colonization or infection for each study period were summarized using local weighted (Loess) regression. RESULTS: We detected no significant change in either IRR and weekly trend in CPE colonization and infection during the 2 study periods. A shift from KPC to other CPE mechanisms (OXA-48 and VIM) was observed during period 2. Compared to period 1, during period 2 the IRR of colonization and infection with CR-Ab increased 7.5- and 5.5-fold, respectively. Genome sequencing showed that all CR-Ab strains belonged to the CC92/IC2 clonal lineage. Clinical strains clustered closely into a single monophyletic group in 1 of the 3 centers, whereas they segregated in 2 different clusters in the other 2 centers, which strongly indicates horizontal transmission. CONCLUSIONS: Our findings indicate the need to conduct infection control activities targeted against the spread of antimicrobial resistance between and within hospitals during the COVID-19 pandemic, and if necessary, remodulating them according to the new organizational structures imposed by the pandemic.


Subject(s)
Acinetobacter baumannii , COVID-19 , Carbapenem-Resistant Enterobacteriaceae , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins , COVID-19/epidemiology , Carbapenems/pharmacology , Cross-Sectional Studies , Humans , Intensive Care Units , Pandemics , beta-Lactamases
10.
Am J Infect Control ; 49(6): 792-799, 2021 06.
Article in English | MEDLINE | ID: covidwho-1269213

ABSTRACT

BACKGROUND: Antibiotic-resistant Acinetobacter species are a growing public health threat, yet are not nationally notifiable, and most states do not mandate reporting. Additionally, there are no standardized methods to detect Acinetobacter species colonization. METHODS: An outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) was identified at a Utah ventilator unit in a skilled nursing facility. An investigation was conducted to identify transmission modes in order to control spread of CRAB. Culture-based methods were used to identify patient colonization and environmental contamination in the facility. RESULTS: Of the 47 patients screened, OXA-23-producing CRAB were detected in 10 patients (21%), with 7 patients (15%) having been transferred from out-of-state facilities. Of patients who screened positive, 60% did not exhibit any signs or symptoms of active infection by chart review. A total of 38 environmental samples were collected and CRAB was recovered from 37% of those samples. Whole genome sequencing analyses of patient and environmental isolates suggested repeated CRAB introduction into the facility and highlighted the role of shared equipment in transmission. CONCLUSIONS: The investigation demonstrated this ventilated skilled nursing facility was an important reservoir for CRAB in the community and highlights the need for improved surveillance, strengthened infection control and inter-facility communication within and across states.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Cross Infection , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter Infections/prevention & control , Acinetobacter baumannii/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins , Carbapenems/pharmacology , Cross Infection/drug therapy , Cross Infection/epidemiology , Cross Infection/prevention & control , Disease Outbreaks , Humans , Infection Control , Microbial Sensitivity Tests , Skilled Nursing Facilities , Utah/epidemiology , beta-Lactamases/genetics
11.
MMWR Morb Mortal Wkly Rep ; 69(48): 1827-1831, 2020 Dec 04.
Article in English | MEDLINE | ID: covidwho-1000679

ABSTRACT

Carbapenem-resistant Acinetobacter baumannii (CRAB), an opportunistic pathogen primarily associated with hospital-acquired infections, is an urgent public health threat (1). In health care facilities, CRAB readily contaminates the patient care environment and health care providers' hands, survives for extended periods on dry surfaces, and can be spread by asymptomatically colonized persons; these factors make CRAB outbreaks in acute care hospitals difficult to control (2,3). On May 28, 2020, a New Jersey hospital (hospital A) reported a cluster of CRAB infections during a surge in patients hospitalized with coronavirus disease 2019 (COVID-19). Hospital A and the New Jersey Department of Health (NJDOH) conducted an investigation, and identified 34 patients with hospital-acquired multidrug-resistant CRAB infection or colonization during February-July 2020, including 21 (62%) who were admitted to two intensive care units (ICUs) dedicated to caring for COVID-19 patients. In late March, increasing COVID-19-related hospitalizations led to shortages in personnel, personal protective equipment (PPE), and medical equipment, resulting in changes to conventional infection prevention and control (IPC) practices. In late May, hospital A resumed normal operations, including standard IPC measures, as COVID-19 hospitalizations decreased, lessening the impact of personnel and supply chain shortages on hospital functions. CRAB cases subsequently returned to a pre-COVID-19 baseline of none to two cases monthly. The occurrence of this cluster underscores the potential for multidrug-resistant organisms (MDROs) to spread during events when standard hospital practices might be disrupted; conventional IPC strategies should be reinstated as soon as capacity and resources allow.


Subject(s)
Acinetobacter Infections/epidemiology , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Carbapenems/pharmacology , Cross Infection/epidemiology , Drug Resistance, Bacterial , COVID-19/epidemiology , COVID-19/therapy , Female , Hospitals , Humans , Male , Middle Aged , New Jersey/epidemiology , Patient Admission/statistics & numerical data
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