Acinetobacter Baumannii Complex Research Articles

Assessing Clinician Utilization of Next-Generation Antibiotics Against Resistant Gram-Negative Infections in U.S. Hospitals : A Retrospective Cohort Study.

The U.S. antibiotic market failure has threatened future innovation and supply. Understanding when and why clinicians underutilize recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development and potential market entry rewards. To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, plazomicin, eravacycline, imipenem-relebactam-cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics). Retrospective cohort. 619 U.S. hospitals. Adult inpatients. Quarterly percentage change in antibiotic use was calculated using weighted linear regression. Machine learning selected candidate variables, and mixed models identified factors associated with new (vs. traditional) antibiotic use in DTR infections. Between quarter 1 of 2016 and quarter 2 of 2021, ceftolozane-tazobactam (approved 2014) and ceftazidime-avibactam (2015) predominated new antibiotic usage whereas subsequently approved gram-negative antibiotics saw relatively sluggish uptake. Among gram-negative infection hospitalizations, 0.7% (2551 [2631 episodes] of 362 142) displayed DTR pathogens. Patients were treated exclusively using traditional agents in 1091 of 2631 DTR episodes (41.5%), including "reserve" antibiotics such as polymyxins, aminoglycosides, and tigecycline in 865 of 1091 episodes (79.3%). Patients with bacteremia and chronic diseases had greater adjusted probabilities and those with do-not-resuscitate status, acute liver failure, and Acinetobacter baumannii complex and other nonpseudomonal nonfermenter pathogens had lower adjusted probabilities of receiving newer (vs. traditional) antibiotics for DTR infections, respectively. Availability of susceptibility testing for new antibiotics increased probability of usage. Residual confounding. Despite FDA approval of 7 next-generation gram-negative antibiotics between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety-efficacy profiles. Future antibiotics with innovative mechanisms targeting untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization. U.S. Food and Drug Administration; NIH Intramural Research Program.

Carbapenem-resistant Acinetobacter baumannii complex in the United States—An epidemiological and molecular description of isolates collected through the Emerging Infections Program, 2019

BackgroundUnderstanding the epidemiology of carbapenem-resistant A. baumannii complex (CRAB) and the patients impacted is an important step towards informing better infection prevention and control practices and improving public health response. MethodsActive, population-based surveillance was conducted for CRAB in 9 U.S. sites from January 1-December 31, 2019. Medical records were reviewed, isolates were collected and characterized including antimicrobial susceptibility testing and whole genome sequencing. ResultsAmong 136 incident cases in 2019, 66 isolates were collected and characterized; 56.5% were from cases who were male, 54.5% were from persons of Black or African American race with non-Hispanic ethnicity, and the median age was 63.5 years. Most isolates, 77.2%, were isolated from urine, and 50.0% were collected in the outpatient setting; 72.7% of isolates harbored an acquired carbapenemase gene (aCP), predominantly blaOXA-23 or blaOXA-24/40; however, an isolate with blaNDM was identified. The antimicrobial agent with the most in vitro activity was cefiderocol (96.9% of isolates were susceptible). ConclusionsOur surveillance found that CRAB isolates in the U.S. commonly harbor an aCP, have an antimicrobial susceptibility profile that is defined as difficult-to-treat resistance, and epidemiologically are similar regardless of the presence of an aCP.

The causes of bacterial bloodstream infections and antimicrobial resistance patterns in children attending a secondary care hospital in Bhaktapur, Nepal, 2017-2022: a retrospective study.

Data on antimicrobial resistance (AMR) among children in Nepal are limited. Here we have characterized the causes of bacterial bloodstream infections (BSIs), antimicrobial resistance patterns and the mechanisms of β-lactamase production in Enterobacterales among children attending outpatient and inpatient departments of a secondary care paediatric hospital in Nepal. We retrospectively collected demographic and clinical data of culture-proven bacterial BSIs between January 2017 and December 2022 among children <18 years attending a 50-bedded paediatric hospital. Stored isolates were subcultured for antimicrobial susceptibility testing against commonly used antimicrobials. Enterobacterales displaying non-susceptibility to β-lactams were phenotypically and genotypically investigated for ESBLs, plasmid-mediated AmpC (pAmpC) β-lactamases and carbapenemases. A total of 377 significant bacteria were isolated from 27 366 blood cultures. Among 91 neonates with a BSI, Klebsiella pneumoniae (n = 39, 42.4%), Pseudomonas aeruginosa (n = 15, 16.3%) and Acinetobacter baumannii complex (n = 13, 14.1%) were most common. In the non-neonates, 275/285 (96.5%) infections were community-acquired including Staphylococcus aureus (n = 89, 32.4%), Salmonella Typhi (n = 54, 19.6%) and Streptococcus pneumoniae (n = 32, 11.6%). Among the 98 S. aureus, 29 (29.6%) were methicillin-resistant Staphylococcus aureus. K. pneumoniae and Escherichia coli demonstrated non-susceptibility to extended-spectrum cephalosporins and carbapenems in both community and hospital-acquired cases. For E. coli and K. pneumoniae, blaCTX-M (45/46), blaEBC (7/10) and blaOXA-48 (5/6) were common among their respective groups. We determined significant levels of AMR among children attending a secondary care paediatric hospital with BSI in Nepal. Nationwide surveillance and implementation of antimicrobial stewardship policies are needed to combat the challenge imposed by AMR.

1449. Evaluation of Cloud-Based Automated Analytic Pipelines for Whole Genome Sequencing Analysis of Multidrug-Resistant Gram-Negative Organism Outbreaks

Abstract Background Clinical implementation of whole genome sequencing (WGS) has been identified as the optimal approach to identify transmission of multidrug-resistant (MDR) organisms in the healthcare setting. Although WGS capabilities are becoming more common in clinical laboratories, analysis and interpretation of results is still a barrier to implementation. The purpose of this study was to evaluate cloud-based automated analytic pipelines to aid with WGS analysis of MDR gram-negative organisms as part of outbreak investigations. Methods A convenience set of MDR Enterobacterales (n: 142), Acinetobacter baumannii complex (n: 14) and Pseudomonas aeruginosa (n:29) isolates were WGS on Illumina sequencing platforms. The FASTQ files were uploaded to AREScloud (Ares Genetics, an OpGen group company) and to EPISEQ CS (bioMérieux) for whole genome or core genome multi-locus sequence typing (wgMLST/cgMLST) with dendrogram creation. Results were compared to traditional 7 gene MLST schema. Ease-of-use and additional tools were compared between pipelines. Results AREScloud and EPISEQ CS generated similar dendrograms for all organisms evaluated (examples provided in Figures 1 &amp; 2). EPISEQ CS provided preset similarity thresholds based on percent relatedness to define clusters simplifying outbreak analysis, whereas AREScloud allowed users to define allelic difference cutoffs. Although the wgMLST/cgMLST clusters aligned with traditional MLST types, not all isolates assigned to a similar MLST were identified as part of a related cluster demonstrating increased resolution of wgMLST and cgMLST phylogenetic assessments. Table 1 compares the features between the two pipelines. Dendrogram generated for Escherichia coli (EPISEQ CS) Dendrogram generated for Escherichia coli (AREScloud) Comparison of features between EPISEQ CS and AREScloud for phylogenetic analysis Conclusion Both cloud-based tools perform comparably for assessing phylogenetic relatedness compared to traditional MLST. Preset similarity thresholds available with EPISEQ CS provide ease-of-use for cluster assessment. Additional features, such as resistome and virulome analysis, are available by both pipelines. Predictive WGS-AST is an additional asset available with AREScloud. Disclosures Karen C. Carroll, MD, Abbott Diagnostics: Board Member|Co-Diagnostics, Inc.: Board Member|Great Basin: Grant/Research Support|Meridian Diagnostics: Grant/Research Support|Pattern Diagnostics: Advisor/Consultant|Pattern Diagnostics: Stocks/Bonds|Qiagen, Inc.: Grant/Research Support|Scanogen: Advisor/Consultant|Scanogen: Grant/Research Support Patricia J. Simner, PhD, Affinity Biosensors: Grant/Research Support|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|Entasis: Advisor/Consultant|GeneCapture: Stocks/Bonds|Merck: Advisor/Consultant|OpGen Inc: Board Member|OpGen Inc: Grant/Research Support|OpGen Inc: Honoraria|Qiagen Sciences Inc: Advisor/Consultant|Qiagen Sciences Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|T2 Biosystems: Grant/Research Support

2458. Carbapenem-resistant Acinetobacter baumannii complex infections and SARS-CoV-2 positivity in 9 U.S. sites, 2020-2022

Abstract Background Reports have shown increases in carbapenem-resistant Acinetobacter baumannii complex (CRAB) infections during the COVID-19 pandemic. To describe the effect of SARS-CoV-2 (SC2) infection on CRAB infection epidemiology, we analyzed data from the Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) population-based CRAB surveillance in 9 U.S. sites. Methods: In 2020–22, among surveillance-area residents, an incident CRAB case was defined as the 1st isolation of A. baumannii complex resistant to ≥1 carbapenem (excluding ertapenem) from a normally sterile site or urine (or lower respiratory tract or wound, as of 2021) in a 30-day period. We included cases that underwent chart review. Cases with a culture collected ≥3 days after hospitalization were considered hospital-onset (HO); all others were community-onset (CO). Cases with a SC2+ test ≤14 days before the incident CRAB culture were compared to other CRAB cases. Results Of 406 CRAB cases representing 344 patients, 26 (6%) cases in 24 patients were SC2+. SC2+ case-patients were more likely to be female than other CRAB case-patients (58% vs 34%, p=0.02); there were no significant differences in race/ethnicity or age distribution. SC2+ cases were more likely to be obese (42% vs. 23%, p=0.03), have bacteremia (23% vs. 10%, p=0.05), and to have died (39% vs. 16%, p=0.003). SC2+ cases were also more likely to require hospitalization (100% vs. 75%, p=0.005) and have HO CRAB (58% vs 29%, p=0.003). Median hospital length of stay was longer in SC2+ cases (19 days, interquartile range [IQR] 8–30) than in other CRAB cases (14 days, IQR 7–26, p=0.42), but there were no significant differences in the percentages with intensive care unit stays or mechanical ventilation in the 7 days before CRAB culture. Culture sources and infection types in SC2+ cases vs. other CRAB cases are shown in the Table. Conclusion A small minority of CRAB patients were infected with SC2+ in the 14 days before CRAB infection but these patients had epidemiological and clinical features that were distinct from other CRAB patients, including higher mortality. Infection control and clinical measures are needed to protect SC2+ patients from secondary bacterial infection and mitigate poor outcomes in those with SC2 and CRAB infection. Disclosures Ghinwa Dumyati, MD, Pfizer: Grant/Research Support Rebecca Tsay, MPH, CDC: Grant/Research Support

Can high procalcitonin levels be a biomarker for detecting multidrug-resistant Gram-negative bacteremia?

Aims: Clinicians prefer broad-spectrum empirical antibiotic therapy in patients with suspected bloodstream infection (BSI) due to long test turnaround times of conventional methods. We aimed to assess the contribution of procalcitonin (PCT) to the selection of antibiotics to be used in empirical treatment.&#x0D; Methods: The results of inpatients whose blood cultures and samples for PCT tests had been sent simultaneously between 2018 and 2022 were analyzed retrospectively. Antibiotic susceptibility results of Enterobacteriaceae, Acinetobacter baumannii complex and Pseudomonas aeruginosa, were evaluated for multidrug-resistance (MDR). &#x0D; Results: Results of 1206 patients who met the inclusion criteria were included in the study. The PCT median value in BSIs caused by the Gram-negative bacteria found to be statistically significantly higher than those caused by the Gram-positive bacteria, fungal and polymicrobial infections (p

Assessment of cefiderocol disk diffusion versus broth microdilution results when tested against Acinetobacter baumannii complex clinical isolates.

The aim of this study was to evaluate the correlation between inhibitory zones and minimum inhibitory concentrations (MICs) when testing cefiderocol against Acinetobacter baumannii complex using disk diffusion and the broth microdilution (BMD) method according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Four-hundred and sixty-eight non-duplicated A. baumannii complex clinical isolates were collected from 56 hospitals of the China Antimicrobial Surveillance Network from 2019 to 2021. BMD using iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) and standard disk diffusion methods were performed according to CLSI guidelines. Results were interpreted according to the CLSI and EUCAST breakpoints. Categorical agreement (CA), minor error (mE), major error (ME), and very major error (VME) were calculated for disk diffusion methods. The susceptibilities of all A. baumannii complex isolates by BMD were 98.7% (CLSI) and 97.6% (EUCAST). For all A. baumannii complex isolates, CA was 98.1% (CLSI) and 97.0% (EUCAST), with 0.9% (CLSI) and 1.9% (EUCAST) of VME, respectively. For the carbapenem-susceptible A. baumannii complex, the CA was 100%, with no mE or VME using both CLSI and EUCAST breakpoints. For carbapenem-resistant A. baumannii complex, CA was 97.5% (CLSI) and 96.2% (EUCAST), with 1.1% (CLSI) and 2.5% (EUCAST) of VME, respectively. Regarding the difficult-to-treat resistance A. baumannii complex isolates, CA was 97.6% (CLSI) and 95.7% (EUCAST), with 1.2% (CLSI) and 3.1% (EUCAST) of VME, respectively. Cefiderocol disk diffusion was difficult to assess in this study. Very few isolates were resistant to cefiderocol by BMD using CLSI breakpoint, and these were categorized as susceptible with the disk diffusion test. This study did, however, show that the main proportion of A. baumannii isolates were susceptible to cefiderocol by BMD, including carbapenem-resistant A. baumannii. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii is a major global health concern due to its high prevalence and limited treatment options. Cefiderocol is the only novel Food and Drug Administration (FDA)-approved β-lactam agent for the salvage treatment of carbapenem-resistant A. baumannii infection. Currently, a commercial automated susceptibility testing panel of cefiderocol is unavailable. Both the preparation of iron-depleted cation-adjusted Mueller-Hinton broth and the performance of broth microdilution are cumbersome in routine microbiology laboratories. A disk diffusion method is convenient for cefiderocol antimicrobial susceptibility testing, but limited data are available specifically for A. baumannii clinical isolates. Moreover, the Clinical and Laboratory Standards Institute published revisions to the A. baumannii cefiderocol disk diffusion breakpoints in 2022. Hence, we evaluated the performance of cefiderocol disk diffusion compared with the reference BMD against A. baumannii clinical isolates, especially those with cefiderocol zone diameters ≤ 14 mm.

Distribution and Drug Resistance of Bacterial Infection in Hospitalized Patients at the Respiratory Department before and after the COVID-19 Pandemic in Guangzhou, China.

Since COVID-19 might have a lasting impact on global public health, it is crucial to analyze its effect on drug-resistant bacterial infections in the respiratory system for the prevention and control of hospital infections. This work aimed to investigate the impact of the COVID-19 outbreak on the clinical distribution and antibiotic resistance of bacterial infection among hospitalized patients in the respiratory unit in order to establish strategies to control antibiotic-resistant infections. Electronic clinical data registry records from 2018 to 2022 were retrospectively analyzed. A total of 36,829 clinical specimens, including sputum, bronchoalveolar lavage fluid, blood, and urine, were collected from 16,073 patients admitted to the Guangzhou First People's Hospital from January 2018 to December 2022. Among them, 2209 samples were culture-positive. The bacterial isolation rates of different types of samples showed a similar trend from 2019 to 2022, with an increase in 2020 and 2022 and a decrease in 2021. Different bacterial species were separated from different types of samples. The most reported pathogens were identified in sputum samples. Gram-positive isolates were prevalent in urine samples, while Gram-negative bacilli were the predominant pathogenic bacteria isolated from respiratory tract and blood samples. Pseudomonas aeruginosa (P. aeruginosa), Acinetobacter baumannii (A. baumannii) complex, and Klebsiella pneumoniae (K. pneumoniae) were the most abundant Gram-negative bacteria in sputum samples, of which A. baumannii complex had the highest resistance to all tested antibiotics except colistin. Notably, there has been a substantial prevalence of carbapenem-resistant P. aeruginosa, A. baumannii, and K. pneumoniae in the past five years. This alarming situation calls for greater attention and precaution with prescribed antibiotics to limit the generation and spread of new multidrug-resistant bacteria and improve therapeutic management.

Aspectos microbiológicos de la colonización/infección respiratoria causada por Serratia marcescens: a propósito de un caso

The case report describes the arrival of a tracheal aspirate sample from a male patient with a history of prior treatment with carbapenems and colistin for several days. The sample was sown, among other media, on Mac Conkey agar and the presence of two types of colonies was identified, one of which produced an intense red pigment. Identification was made using the VITEK 2 identification system, revealing the presence of Serratia marcescens and Acinetobacter baumannii complex in the sample. The importance of adequate antimicrobial identification and use in the investigation of respiratory infections caused by intrinsically resistant bacteria such as Serratia marcescens and Acinetobacter baumannii is emphasized. In addition, resistance to antibiotics and the possible derepression of inducible AmpC-type β-lactamases during treatment are discussed. The presence of pseudohemoptysis and the production of prodigiosin by Serratia marcescens may be useful in the identification and management of respiratory infections.

NON-FERMENTING GRAM-NEGATIVE BACTERIA IN BLOOD CULTURE: A MENACE IN INTENSIVE CARE UNIT SETTINGS

Objective: To know the prevalence of NFGNB isolated from blood culture specimens and their antibiotic sensitivity pattern in intensive care units. Methods: A total of 3393 blood samples during 1 year were received from patients admitted in various ICUs. 5–7 mL blood was aseptically collected and added in BACTEC bottles and then subsequently incubated in BD BACTECTM (FX40) fluorescent series instrument for up to 5 days. After incubation period, positive samples were processed for gram stain and subsequently sub-cultured on blood agar and MacConkey agar. These plates were incubated at 37°C for 24 h. Further identification and antimicrobial susceptibility testing of NFGNB were carried out by Vitek-2 Compact (Biomerieux India) as per the standard operating procedures. Results: Out of 3393 samples 696 samples showed growth, out of which 96 (13.79%) were Gram-positive cocci, 36 (5.17%) were Candida spp., and 564 (81.03%) were Gram-negative bacilli (GNB). Among 564 GNB, 453(80.31%) were lactose fermenter and 111 (19.68%) were non-lactose fermenters. One (0.53%) isolate of Aeromonas hydrophila was excluded from this study. Among 110 NFGNB, Acinetobacter baumannii complex (41.66%) was the most predominant followed by Pseudomonas aeruginosa (32.72%). Amikacin was the most sensitive drug for all the NFGNB isolates followed by Piperacillin/Tazobactam. Stenotrophomonas maltophilia showed excellent susceptibility to minocycline (83.33%) followed by ceftazidime (66.66%). Burkholderia cepacia showed good susceptibility to Trimethoprim/Sulfamethoxazole. Conclusion: Increasing antimicrobial resistance in NFGNB and their intrinsic or acquired resistance to many antibiotics makes them more lethal. It is therefore recommended to have quality guidelines on the “rational use of antibiotics” which need to be implemented strictly

Resistome-based surveillance identifies ESKAPE pathogens as the predominant gram-negative organisms circulating in veterinary hospitals.

Healthcare-associated infections (HCAIs) associated with extended-spectrum cephalosporin-resistant gram-negative (ESC-R GN) bacteria are an emerging concern in veterinary hospitals, especially in companion animal intensive care units (ICUs). To understand the molecular epidemiology of ESC-R GN isolates in two veterinary hospitals (equine and small animal), a 6-month pilot study was performed during which fecal and environmental samples were obtained twice from selected patients, upon ICU admission and after 48 h of hospitalization. In total, 295 ESC-R GNs were analyzed using the Acuitas Resistome® Test (OpGen, Maryland, US), a PCR-based assay screening for 50 antimicrobial resistance gene families encoding for production of extended-spectrum beta-lactamase (ESBLs), TEM/SHV/OXA or AmpC beta-lactamases and carbapenemases. Combining organism identification and antimicrobial susceptibility data to genotyping results, unique "Acuitas profiles" were generated that can be used for fast typing the isolates and tracking transmission events. ESKAPE GN pathogens were the most prevalent ESC-R GN isolates circulating in both the small animal and equine hospitals, consisting of Enterobacter cloacae complex (21.7%), Pseudomonas aeruginosa (20%), Klebsiella pneumoniae (15.9%), and Acinetobacter baumannii complex (13.6%) followed by Escherichia coli (12.2%), most harboring a combination of genes encoding for beta-lactamases and ESBLs. Some ESKAPE genotypes showed likely intra-hospital transmission, including E. cloacae (two genotypes, one carrying SHV4, SHV5, and TEM7 and the other TEM1, TEM3, and TEM7 enzymes) in the equine and K. pneumoniae (SHV1, SHV5, and DHA1-positive) in the small animal ICUs, respectively. Furthermore, P. aeruginosa (carrying OXA-50), A. baumannii complex (OXA-51), and E. coli (CTX-M-1) genotypes were isolated across both hospitals, suggesting possible transfer mediated via movement of staff and students. Importantly, isolates carrying transmissible resistance to last-resort antimicrobials (i.e. carbapenems) were identified within the hospital environments, consisting of three environmental Acinetobacter spp. harboring blaOXA - 23 and one clinical E. coli with blaOXA - 48. We describe the widespread occurrence of ESKAPE gram-negative organisms in veterinary ICU patients and hospital environments. Findings from this project provide baseline data on the epidemiology of ESKAPE pathogens in veterinary settings, which can inform infection control policies to aid in patient management and prevent transmission of nosocomial infections associated with these pathogens.

Suppression of tomato wilt by cell-free supernatants of Acinetobacter baumannii isolates from wild cacao from the Colombian Amazon

Tomato vascular wilt caused by Fusarium oxysporum f. sp. lycopersici (Fol) is one of the most limiting diseases of this crop. The use of fungicides and varieties resistant to the pathogen has not provided adequate control of the disease. In this study, siderophore-producing bacteria isolated from wild cocoa trees from the Colombian Amazon were characterized to identify prominent strategies for plant protection. The isolates were taxonomically classified into five different genera. Eight of the fourteen were identified as bacteria of the Acinetobacter baumannii complex. Isolates CBIO024, CBIO086, CBIO117, CBIO123, and CBIO159 belonging to this complex showed the highest efficiency in siderophore synthesis, producing these molecules in a range of 91–129 µmol/L deferoxamine mesylate equivalents. A reduction in disease severity of up to 45% was obtained when plants were pretreated with CBIO117 siderophore-rich cell-free supernatant (SodSid). Regarding the mechanism of action that caused antagonistic activity against Fol, it was found that plants infected only with Fol and plants pretreated with SodSid CBIO117 and infected with Fol showed higher levels of PR1 and ERF1 gene expression than control plants. In contrast, MYC2 gene expression was not induced by the SodSid CBIO117 application. However, it was upregulated in plants infected with Fol and plants pretreated with SodSid CBIO117 and infected with the pathogen. In addition to the disease suppression exerted by SodSid CBIO117, the results suggest that the mechanism underlying this effect is related to an induction of systemic defense through the salicylic acid, ethylene, and priming defense via the jasmonic acid pathway.Graphical abstract

Phenotypical and molecular characterization of Acinetobacter spp. isolated from a pharmaceutical facility.

Characterizing microorganisms according to different criteria is useful when investigating sources of microbiological contamination in the pharmaceutical industry. The aim of this study was to characterize 38 Acinetobacter baumannii complex strains isolated from a biopharmaceutical industry by 16S rRNA sequencing, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS), multilocus sequence typing (MLST), antimicrobial susceptibility profile, biofilm formation, and sensibility to disinfectants. Thirty-three (86.9%) strains were identified by 16S rRNA gene sequencing as A. seifertii/pitti/nosocomialis/lactucae, four (10.5%) as A. baumannii, and one (2.6%) as A. vivianii/courvalini. MALDI-TOF/MS did not identify one strain, and incorrectly identified 30/37 (81.1%) strains as A. baumannii. Strains were assigned to 12 different STs, of which nine were newly defined in this study (STs 2091-2099). Twenty-six (68.4%) strains showed resistance to amikacin and gentamicin. Thirty-three (86.8%) strains were classified as moderately or strongly adherent on polystyrene. Alcohol 70%/15 min and quaternary ammonium 0.08%/20 min were not able to eliminate the biofilm formed, but sodium hypochlorite 0.1%/15 min was efficient. In conclusion, improved methods are needed to improve the identification of Acinetobacter strains in pharmaceutical industries. This organism is of particular concern as it forms recalcitrant biofilms, leading to persistence in the manufacturing environment and increased risk of product contamination.

Mortality and Outcomes of Patients Infected with Extensively Drug-Resistant Bacteria Admitted to Intensive Care Units

Background: The emergence of antimicrobial-resistant pathogens in intensive care units (ICU) makes treatment of these infections very difficult. Objectives: This study aimed to survey the resistance phenotype, risk factors, and possible treatment options for hospital-acquired infections (HAI) at ICUs in a referral university hospital. Methods: Samples were prepared from ICU patients with HAIs. Pathogens were isolated, and the resistance phenotype, prescribed antibiotics, mortality rate, associated risk factors, and clonal relationship of the isolates were assessed. Results: From 100 patients admitted to ICUs, 76 (76%) showed clinical symptoms of HAIs. The most common sources of infection were lung secretions (51.8%). The isolated bacteria were Gram-negative (77, 90.6%) and Gram-positive (9.4%). The most common isolated microorganism was the Acinetobacter baumannii complex (63.5%). The most effective antimicrobials were colistin (96.1%) and linezolid (100%) for Gram-negative and Gram-positive isolates, respectively. An extensively drug-resistant (XDR) phenotype was documented in all isolates of A. baumannii, Pseudomonas aeruginosa, and Serratia marcescens. The XDR phenotype was a significant risk factor only for mortality. A. baumannii had the highest mortality rate (66.6%) among all the isolates. While A. baumannii strains had limited diversity, the other species were highly divergent. Conclusions: The results revealed a high mortality rate for Gram-negative isolates, especially in adenosine triphosphate-binding cassette (ABC). The high genetic similarities of ABC strains might be an indication of neglecting infection control prevention. The use of cotrimoxazole and colistin instead of carbapenems can be promising for mortality reduction in the studied ICUs.

In vitro activity of cefiderocol against MBL-producing Gram-negative bacteria collected in North America and Europe in five consecutive annual multinational SIDERO-WT surveillance studies (2014-2019).

To evaluate the in vitro antibacterial activity of cefiderocol, a siderophore cephalosporin against MBL-producing clinical isolates. MBL-producing strains were selected from clinical isolates of Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii complex collected in North America and Europe in five consecutive annual multinational SIDERO-WT surveillance studies from 2014 to 2019. MICs of cefiderocol and comparator agents were determined by the broth microdilution method according to the CLSI guideline. A total of 452 MBL-producing strains consisting of 200 Enterobacterales, 227 P. aeruginosa and 25 A. baumannii complex were identified. The highest number of MBL-producing Enterobacterales strains were detected in Greece. MBL-producing strains of both P. aeruginosa and A. baumannii complex were isolated most frequently in Russia. For Enterobacterales, 91.5% or 67.5% of MBL-producing strains had cefiderocol MIC values ≤4 mg/L (CLSI susceptibility breakpoint) or ≤2 mg/L (EUCAST susceptibility breakpoint), respectively. All MIC values of cefiderocol for MBL-producing P. aeruginosa strains were ≤4 mg/L (CLSI susceptibility breakpoint), and 97.4% of them had cefiderocol MIC values ≤2 mg/L (EUCAST susceptibility breakpoint). For A. baumannii complex, 60.0% or 44.0% of MBL-producing strains had cefiderocol MIC values ≤4 mg/L (CLSI susceptibility breakpoint) or ≤2 mg/L (EUCAST pharmacokinetic-pharmacodynamic susceptibility breakpoint), respectively. Against all types of MBL-producing strains, MIC distribution curves of cefiderocol were located in the lowest numerical values, compared with other β-lactams and β-lactam/β-lactamase inhibitor combinations tested and ciprofloxacin. Although the types of MBL-producing strains isolated by country varied, cefiderocol showed potent in vitro activity against all types of MBL-producing Gram-negative bacteria regardless of the bacterial species.

Achieving pre-eminence of antimicrobial resistance among non-fermenting Gram-negative bacilli causing septicemia in intensive care units: A single center study of a tertiary care hospital.

Bloodstream infections in the intensive care unit have always been a global healthcare challenge. The present study was conducted with the aim to evaluate the yearly trend of antibiotic resistance in non-fermenting Gram-negative bacilli (NFGNB) causing septicemia in intensive care units. Blood samples were collected from the patients admitted in various intensive care units and processed for isolation and identification of non-fermenting Gram-negative bacilli. The isolated bacterial strains were subjected to antibiotic susceptibility testing as per standard operating procedures. Out of 3632 blood samples, 977 (26.9%) samples showed microbial growth, of which 10.1% were Gram positive cocci, 8.7% were Gram negative bacilli (Enterobacterales), 7% were NFGNB and 1% were Candida spp. Increasing resistance among Acinetobacter baumannii complex was observed to ceftazidime, cefepime, amikacin, ciprofloxacin, levofloxacin, meropenem and trimethoprim-sulfamethoxazole. Moreover, Pseudomonas aeruginosa strains were found to be associated with increased resistance to ciprofloxacin, levofloxacin, ceftazidime and meropenem. A substantial increase in resistance levels was observed among Stenotrophomonas maltophilia and Sphingomonas paucimobilis as well. An increasing trend of antimicrobial resistance in NFGNB envisages the worst consequences in ICUs in the coming years. Therefore, reviewing and strict implementation of the antimicrobial policies including 'rational use of antibiotics' is recommended.

In Vitro Activity of Cefiderocol Against Meropenem-Nonsusceptible Gram-Negative Bacilli with Defined β-Lactamase Carriage: SIDERO-WT Surveillance Studies, 2014-2019.

We examined the in vitro susceptibility of meropenem-nonsusceptible Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex isolates from five consecutive annual SIDERO-WT surveillance studies (2014-2019) to cefiderocol and comparator agents in the context of their carbapenemase carriage. 1,003 Enterobacterales, 1,758 P. aeruginosa, and 2,809 A. baumannii complex isolates from North America and Europe that were meropenem nonsusceptible (CLSI M100, 2022) were molecularly characterized for β-lactamase content by PCR followed by Sanger sequencing or by whole genome sequencing. Among Enterobacterales, 91.5% of metallo-β-lactamase (MBL)-producing, 98.4% of KPC-producing, 97.3% of OXA-48 group-producing, and 98.7% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Among P. aeruginosa, 100% of MBL-producing, 100% of GES carbapenemase-producing, and 99.8% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Among A. baumannii complex, 60.0% of MBL-producing, 95.6% of OXA-23 group-producing, 89.5% of OXA-24 group-producing, 100% of OXA-58 group-producing, and 95.5% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Cefiderocol was inactive against A. baumannii complex isolates carrying a PER or VEB β-lactamase (n = 103; 15.5% susceptible). Ceftazidime-avibactam and ceftolozane-tazobactam were inactive against MBL-carrying and A. baumannii complex isolates; ceftolozane-tazobactam was also inactive against serine carbapenemase-carrying Enterobacterales and P. aeruginosa. In summary, cefiderocol was highly active in vitro against Gram-negative isolates carrying MBLs and serine carbapenemases, as well as carbapenemase-negative, meropenem-nonsusceptible isolates.

Molecular epidemiology of Acinetobacter baumannii complex causing invasive infections in Korean children during 2001–2020

BackgroundAcinetobacter baumannii (AB) has emerged as one of the most problematic pathogens affecting critically ill patients. This study aimed to investigate the longitudinal epidemiology of AB causing invasive diseases in children.MethodsAcinetobacter spp. cultured from sterile body fluids and identified as Acinetobacter calcoaceticus-baumannii (ACB) complexes by automated systems from children aged below 19 years old were prospectively collected during 2001–2020. The discriminative partial sequence of rpoB gene was sequenced to identify the species, and sequence types (STs) were determined. Temporal changes in antimicrobial susceptibilities and STs were analyzed.ResultsIn total, 108 non-duplicate ACB isolates were obtained from patients with invasive infections. The median age was 1.4 (interquartile range, 0.1–7.9) years, and 60.2% (n = 65) were male. Acinetobacter baumannii comprised 55.6% (n = 60) of the isolates, and the 30-day mortality was higher in patients with isolated AB than in those with non-baumannii Acinetobacter spp. (46.7% vs. 8.3%, P < 0.001). After 2010, complete genotype replacement was observed from non-CC92 genotypes to only CC92 genotypes. Carbapenem resistance rates were highest in AB CC92 (94.2%), followed by AB non-CC92 (12.5%) and non-baumannii Acinetobacter spp. (2.1%). During 2014–2017, which included clustered cases of invasive ST395, colistin resistance increased to 62.5% (n = 10/16), showing a mortality rate of 88% during this period.ConclusionComplete genotype replacement of non-CC92 with CC92 genotypes was observed. AB CC92 was extensively drug-resistant, and pandrug resistance was observed depending on the ST, warranting careful monitoring.

Sternum Defektlerinin Rekonstrüksiyonunda Güvenilir Bir Yöntem: Pektoralis Major Kas Flebi ile Negatif Basınçlı Yara Bakım Kombinasyonu

Objective: Sternotomy defects may present mildly as isolated skin separation or severely as mediastinitis. A combination of treatment options can support treatment. Methods: Patients who were treated with pectoralis major flap with the combination of negative pressure wound therapy (NPWT) between 2016-2020, were retrospectively reviewed. Demographic features, microorganisms causing wound infection, flap reconstruction preference, time of hospitalization, remission, recurrence and associated morbidity and mortality data were evaluated. Results: Thirteen patients were included with a mean age of 65.4 years. All patients previously underwent coronary artery bypass graft surgery. Wound cultures from patients were positive in nine (69%). Isolated microorganisms were Staphylococcus spp. (n=4), Klebsiella pneumoniae (n=3) and Acinetobacter baumannii complex (n=2). The most common comorbidities were hypertension (76%) and diabetes mellitus(46%). The average hospital stay was 23.4 days. One patient died on the seventh postoperative day, two had seromas at the flap donor site, and one had hematoma. Conclusion: Pectoralis major muscle flap and NPWT after complete removal of dead tissues is an effective method to repair and treat sternum defects.

Evaluation of Early Reading of Broth Microdilution Technique for Polymyxin B.

Delay in the results of standard phenotypic susceptibility tests is the main obstacle to adequate antibiotic treatment. For this reason, the European Committee for Antimicrobial Susceptibility Testing has proposed the Rapid Antimicrobial Susceptibility Testing for the disk diffusion method directly from blood culture. However, to date, there are no studies evaluating early readings of polymyxin B broth microdilution (BMD), the only standardized methodology for assessing susceptibility to polymyxins. This study aimed to evaluate modifications in the BMD technique for polymyxin B using fewer antibiotic dilutions and reading after an incubation time of 8-9 hr (early reading) in comparison to 16-20 hr of incubation (standard reading) for isolates of Enterobacterales, Acinetobacter baumannii complex, and Pseudomonas aeruginosa. A total of 192 isolates of gram-negative bacteria were evaluated and the minimum inhibitory concentrations were read after early and standard incubations. The early reading presented 93.2% of essential agreement and 97.9% of categorical agreement with the standard reading of BMD. Only three isolates (2.2%) presented major errors and only one (1.7%) presented a very major error. These results indicate a high agreement between the early and the standard reading times of BMD of polymyxin B.