Ampicillin-Sulbactam for Carbapenem-Susceptible Acinetobacter baumannii Pneumonia: A Case for High-Dose, Continuous Infusion Dosing Strategy in the Trauma ICU.

Background: The optimal ampicillin-sulbactam dosing regimen for carbapenem-susceptible Acinetobacter baumannii isolates in critically ill trauma patients has not been clearly defined. One strategy to provide the adequate sulbactam dose includes high-dose continuous infusion. Case(s) Description: We present three cases of critically ill trauma patients with augmented renal clearance treated with high-dose ampicillin-sulbactam through an intravenous continuous infusion for ventilator-associated pneumonia. All A. baumannii isolates were susceptible to sulbactam with low minimum inhibitory concentrations. All achieved clinical cure at the end of therapy and no recurrent pneumonia was noted. No clinically substantial adverse effect attributable to ampicillin-sulbactam therapy occurred. Discussion: There is limited evidence to endorse high-dose, continuous infusion ampicillin-sulbactam for treatment of infections caused by carbapenem-susceptible A. baumannii. This report presents three critically ill trauma patients with augmented renal clearance that achieved positive clinical outcomes with higher doses of ampicillin-sulbactam administered through a continuous infusion.

Structure modeling-based characterization of ChnD, the 6-hydroxyhexanoate dehydrogenase from Acinetobacter sp. strain NCIMB 9871.

α,ω-Dicarboxylic acids, ω-aminoalkanoic acids, and α,ω-diaminoalkanes are valuable building blocks for the production of biopolyesters and biopolyamides. One of the key steps in producing these chemicals is the oxidation of ω-hydroxycarboxylic acids using alcohol dehydrogenases (e.g., ChnD of Acinetobacter sp. NCIMB 9871). However, the reaction and structural features of these enzymes remain mostly undiscovered. Thereby, we have investigated characteristics of ChnD based on enzyme kinetics, substrate-docking simulations, and mutation studies. Kinetic analysis revealed a distinct preference of ChnD for medium chain ω-hydroxycarboxylic acids, with the highest catalytic efficiency of 18.0 mM-1s-1 for 12-hydroxydodecanoic acid among C6 to C12 ω-hydroxycarboxylic acids. The high catalytic efficiency was attributed to the positive interactions between the carboxyl group of the substrates and the guanidino group of two arginine residues (i.e., Arg62 and Arg266) in the substrate binding site. The ChnD_R62L variant showed the increased efficiency and affinity, particularly for fatty alcohols (i.e., C6-C10) and branched-chain fatty alcohols, such as 3-methyl-2-buten-1-ol. Overall, this study contributes to the deeper understanding of medium-chain primary aliphatic alcohol dehydrogenases and their applications for the production of industrially relevant chemicals such as α,ω-dicarboxylic acids, ω-aminoalkanoic acids, and α,ω-diaminoalkanes from renewable biomass.

A case of treatment for pulmonary infection caused by multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a major pathogen in hospital-acquired infections notorious for its strong acquired resistance and complex drug resistance mechanisms. Owing to the lack of effective drugs, the mortality rate of extensively drug-resistant A. baumannii pneumonia can reach as high as 65%. This article analyzes a case where a combination of cefoperazone-sulbactam, polymyxin B, and minocycline with rifampicin successfully treated XDR-AB pulmonary infection. Combination therapy is effective and has a particular clinical value.

Competitive inhibition and mutualistic growth in co-infections: deciphering Staphylococcus aureus-Acinetobacter baumannii interaction dynamics.

Staphylococcus aureus (Sa) and Acinetobacter baumannii (Ab) are frequently co-isolated from polymicrobial infections that are severe and refractory to therapy. Here, we apply a combination of wet-lab experiments and in silico modeling to unveil the intricate nature of the Ab/Sa interaction using both, representative laboratory strains and strains co-isolated from clinical samples. This comprehensive methodology allowed uncovering Sa's capability to exert a partial interference on Ab by the expression of phenol-soluble modulins. In addition, we observed a cross-feeding mechanism by which Sa supports the growth of Ab by providing acetoin as an alternative carbon source. This study is the first to dissect the Ab/Sa interaction dynamics wherein competitive and cooperative strategies can intertwine. Through our findings, we illuminate the ecological mechanisms supporting their coexistence in the context of polymicrobial infections. Our research not only enriches our understanding but also opens doors to potential therapeutic avenues in managing these challenging infections.

Evaluation of the in vitro activity of ampicillin-sulbactam and cefoperazone-sulbactam against A. Baumannii by the broth disk elution test.

To evaluate the in vitro activity of ampicillin-sulbactam and cefoperazone-sulbactam against A. baumannii using the broth disk elution testing, a total of 150 A. baumannii isolates were collected from across China between January 2019 and January 2021, including 51 carbapenem-susceptible and 99 carbapenem-resistant isolates. Broth disk elution (BDE) and the broth microdilution (BMD) method were performed for all strains. The concentration range of the BDE was 10/10 µg/mL, 20/20 µg/mL, and 30/30 µg/mL for ampicillin-sulbactam, and 37.5/15 µg/mL, 75/30 µg/mL, 112.5/45 µg/mL, and 150/60 µg/mL for cefoperazone-sulbactam, respectively. Compared with BMD, the BDE results of ampicillin-sulbactam and cefoperazone-sulbactam showed a categorical agreement of 83.3% (125/150) and 95.3% (143/150), with minor errors of 16.7% (25/150) and 4.7% (7/150), respectively. No major error or very major errors were detected. The sensitivity differences by BDE of carbapenem-resistant A. baumannii (CRAb) to different concentrations of ampicillin-sulbactam showed statistically significant (p < 0.017), while those to cefoperazone-sulbactam at 37.5/15 µg/mL, 75/30 µg/mL, and 112.5/45 µg/mL were significant (p < 0.008). However, no significant difference in sensitivity was observed between 112.5/45 µg/mL and 150/60 µg/mL (p > 0.008). In conclusion, the BDE is a reliable and convenient method to detect the in vitro activity of cefoperazone-sulbactam against A. baumannii, and the results could serve as a clinical reference value when deciding whether or not to use high-dose sulbactam for the treatment of A. baumannii infections.

Transcriptomic analysis reveals zinc-mediated virulence and pathogenicity in multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a gram-negative bacterium well known for its multidrug resistance and connection to nosocomial infections under ESKAPE pathogens. This opportunistic pathogen is ubiquitously associated with nosocomial infections, posing significant threats within healthcare environments. Its critical clinical symptoms, namely, meningitis, urinary tract infections, bloodstream infections, ventilator-associated pneumonia, and pneumonia, catalyze the imperative demand for innovative therapeutic interventions. The proposed research focuses on delineating the role of Zinc, a crucial metallo-binding protein and micronutrient integral to bacterial metabolism and virulence, to enhance understanding of the pathogenicity of A. baumannii. RNA sequencing and subsequent DESeq2 analytical methods were used to identify differential gene expressions influenced by zinc exposure. Exploiting the STRING database for functional enrichment analysis has demonstrated the complex molecular mechanisms underlying the enhancement of pathogenicity prompted by Zinc. Moreover, hub genes like gltB, ribD, AIL77834.1, sdhB, nuoI, acsA_1, acoC, accA, accD were predicted using the cytohubba tool in Cytoscape. This investigation underscores the pivotal role of Zinc in the virulence of A. baumannii elucidates the underlying molecular pathways responsible for its pathogenicity. The research further accentuates the need for innovative therapeutic strategies to combat A. baumannii infections, particularly those induced by multidrug-resistant strains.

Current and novel therapies for management of Acinetobacter baumannii-associated pneumonia.

Acinetobacter baumannii is a common pathogen associated with hospital-acquired pneumonia showing increased resistance to carbapenem and colistin antibiotics nowadays. Infections with A. baumannii cause high patient fatalities due to their capability to evade current antimicrobial therapies, emphasizing the urgency of developing viable therapeutics to treat A. baumannii-associated pneumonia. In this review, we explore current and novel therapeutic options for overcoming therapeutic failure when dealing with A. baumannii-associated pneumonia. Among them, antibiotic combination therapy administering several drugs simultaneously or alternately, is one promising approach for optimizing therapeutic success. However, it has been associated with inconsistent and inconclusive therapeutic outcomes across different studies. Therefore, it is critical to undertake additional clinical trials to ascertain the clinical effectiveness of different antibiotic combinations. We also discuss the prospective roles of novel antimicrobial therapies including antimicrobial peptides, bacteriophage-based therapy, repurposed drugs, naturally-occurring compounds, nanoparticle-based therapy, anti-virulence strategies, immunotherapy, photodynamic and sonodynamic therapy, for utilizing them as additional alternative therapy while tackling A. baumannii-associated pneumonia. Importantly, these innovative therapies further require pharmacokinetic and pharmacodynamic evaluation for safety, stability, immunogenicity, toxicity, and tolerability before they can be clinically approved as an alternative rescue therapy for A. baumannii-associated pulmonary infections.

Evolving resistance landscape in gram-negative pathogens: An update on ß-lactam and ß-lactam-inhibitor treatment combinations for carbapenem-resistant organisms.

Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of ß-lactamases diminishing the activity of classic ß-lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of ß-lactamase inhibitors (BLIs) with activity against extended-spectrum ß-lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo-ß-lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem-resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various ß-lactamases including MBL and OXA-enzymes.

Coexistence of ß-lactamase genes and biofilm forming potential among carbapenem-resistant Acinetobacter baumannii in Lahore, Pakistan.

INTRODUCTION: Our goal was to investigate the antimicrobial resistance due to beta-lactamase genes and virulent determinants (biofilm-forming ability) expressed by Acinetobacter collected from health settings in Pakistan. A cross-sectional study was conducted for the molecular characterization of carbapenemases and biofilm-producing strains of Acinetobacter spp. METHODOLOGY: Two twenty-three imipenem-resistant Acinetobacter isolates were analyzed from 2020 to 2023.The combination disk test and modified hodge test were performed. Biofilm forming ability was determined by polystyrene tube assay. Multiplex polymerase chain reaction (PCR) for virulent and biofilm-forming genes, and 16S rRNA sequencing were performed. RESULTS: 118 (52.9%) carbapenem-resistant Acinetobacter (CR-AB) were isolated from wounds and pus, 121 (54.2%) from males, and 92 (41.2%) from 26-50-years-olds. More than 80% of strains produced ß-lactamases and carbapenemases. Based on the PCR amplification of the ITS gene, 174 (78.0%) CR-AB strains were identified from CR-Acinetobacter non-baumannii (ANB). Most CR-AB were strong and moderate biofilm producers. Genetic analysis revealed the blaOXA-23, blaTEM, blaCTX-M blaNDM-1 and blaVIM were prevalent in CR-AB with frequencies 91 (94.8%), 68 (70.8%), 19 (19.7%), 53 (55.2%), 2 (2.0%) respectively. Among virulence genes, OmpA was dominant in CR-AB isolates from wound (83, 86.4%), csuE 63 (80.7%) from non-wound specimens and significantly correlated with blaNDM and blaOXA genes. Phylogenetic analysis revealed three different clades for strains based on specimens. CONCLUSIONS: CR-AB was highly prevalent in Pakistan and associated with wound infections. The genes, blaOXA-23, blaTEM, blaCTX-M, and blaNDM-1 were detected in CR-AB. Most CR-AB were strong biofilm producers with virulent genes OmpA and csuE.

An Ancient Drug for a Modern Era: Minocycline for the Treatment of Multi-Drug-Resistant Acinetobacter baumannii.

INTRODUCTION: Infections caused by Acinetobacter baumannii are a major cause of health concerns in the hospital setting. Moreover, the presence of extreme drug resistance in A. baumannii has made the scenario more challenging due to limited treatment options thereby encouraging the researchers to explore the existing antimicrobial agents to combat the infections caused by them. This study focuses on the susceptibility of multi-drug-resistant A. baumannii (MDR-AB) strains to minocycline and also to colistin. METHODOLOGY: A cross-sectional study was conducted from June 2022 to June 2023. One hundred isolates of​​​​​​ A. baumannii â€‹â€‹â€‹obtained from various clinical samples were sent to Central Laboratory, Department of Microbiology, Sree Balaji Medical College and Hospital, Chrompet, Chennai, India. The antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines, 2022. For the standard antibiotics, the disc diffusion method was performed. For minocycline and colistin, the minimum inhibitory concentration (MIC) was determined using an epsilometer strip (E-strip) test. RESULTS: In this study, 100 isolates of A. baumannii were obtained, and 83% of the isolates were multi-drug-resistant. Among the MDR-AB, 50 (60%) were susceptible to minocycline and 40 (48%) were susceptible to colistin. Out of the 40 colistin-susceptible A. baumannii strains, 29 (73%) were susceptible to minocycline with a statistically significant P-value of <0.05. Among the 43 colistin-resistant A. baumannii strains, 21 (53%) were susceptible to minocycline with a statistically significant P-value of <0.05. CONCLUSIONS: When taking into account the expense of treating carbapenemase-producing Gram-negative bacteria, colistin and minocycline can be used as an alternative drug as they have fewer side effects and are more affordable. Minocycline can be used as an alternative to colistin because it is feasible to convert from an injectable to an oral formulation.

Effective Treatment of Acinetobacter baumannii Ventriculitis With Interventricular Colistin: A Case Report.

Cerebrospinal fluid shunts are the primary treatment for hydrocephalus. However, prolonged external ventricular drain (EVD) use can lead to central nervous system (CNS) infections such as ventriculitis. In the ICU setting, nosocomial infections with gram-negative, multi-drug resistant (MDR) organisms such as Acinetobacter baumannii (AB) prevail, leading to poor outcomes. AB infections are notably challenging due to their genetic drug resistance. Colistin has been reintroduced for use against gram-negative MDR pathogens but has limitations in CNS penetration when administered intravenously. Therefore, intraventricular (IVT) or intrathecal administration of colistin is recommended to enhance its therapeutic reach within the CNS. We present a case of a 22-year-old male admitted after an electric scooter accident with head trauma and hydrocephalus. A ventriculoperitoneal (VP) shunt was inserted, complicated by a nosocomial neuroinfection. Empiric IV therapy with meropenem and vancomycin was initiated. The VP shunt culture identified AB susceptible only to colistin. Intravenous (IV) colistin was added to meropenem with no significant improvement. The addition of IVT colistin significantly improved the patient's neurological condition and reduced inflammatory markers. The patient experienced one myoclonic seizure during IVT colistin treatment, managed with antiepileptics. After multiple unrelated nosocomial complications, the patient was discharged in good condition to rehabilitation. This case suggests that IVT colistin, combined with IV administration, may be preferable over IV colistin alone. Medical staff should be informed about the correct prevention and care of EVD-associated infections.

Fully closed conformation of penicillin-binding protein revealed by structure of PBP2 from Acinetobacter baumannii.

Penicillin-binding protein 2 (PBP2), a vital protein involved in bacterial cell-wall synthesis, serves a target for ß-lactam antibiotics. Acinetobacter baumannii is a pathogen notorious for multidrug resistance; therefore, exploration of PBPs is pivotal in the development of new antimicrobial strategies. In this study, the tertiary structure of PBP2 from A. baumannii (abPBP2) was elucidated using X-ray crystallography. The structural analysis demonstrated notable movement in the head domain, potentially critical for its glycosyltransferase function, suggesting that abPBP2 assumes a fully closed conformation. Our findings offer valuable information for developing novel antimicrobial agents targeting abPBP2 that are applicable in combating multidrug-resistant infections.

Temporal evolution of bacterial species and their antimicrobial resistance characteristics in wound infections of war-related injuries in Ukraine from 2014 to 2023.

BACKGROUND: This study continues surveillance of antimicrobial resistance associated with combat injuries in Ukraine. AIM: To compare species composition, antibiotic resistance profiles, and emergence of new resistance genes between 2014-2020 and 2022-2023. METHODS: Retrospective multicentre microbiological survey in Ukrainian hospitals. Antibiotic susceptibility, whole genome sequencing, and MLST typing were conducted on 154 organisms obtained from 125 casualties from 2022-2023. FINDINGS: The data reveals a predominance of gram-negative bacteria, particularly Acinetobacter baumannii (35.7%), Pseudomonas aeruginosa (14.9%), and Klebsiella pneumoniae (20.7%). High levels of carbapenem resistance was observed among A. baumannii (meropenem 72,2% [(39/54) 95% CI 58.4-83.5], imipenem 66.7% [(36/54) 95% CI 52.5-78.9]), Klebsiella (meropenem 90.6% [(29/32) 95% CI 75.0-98.0], imipenem 81.2% [(26/32) 95% CI 63.6-92.8]), and P. aeruginosa (meropenem 47.8% [(11/23) 95% CI 26.8-69.4], imipenem 60.8% [(14/23) 95% CI 38.5-80.3]) strains. A. baumannii ST-78 and ST-400 were prevalent from 2014 to 2020, while 5 strains of ST-1077 were newly identified. Pseudomonas aeruginosa strains showed diversity across 16 sequence types (STs), with ST-773 increasing in frequency and new STs emerging, but lacking carbapenemase genes. K. pneumoniae exhibited increased genetic diversity over time, with three STs from 2014 to 2020 and six new STs, including blaNDM-1, blaOXA-48, and blaKPC2 carriers, in recent years. CONCLUSION: There is a growing prevalence of multidrug resistant isolates from globally distributed sequence types.

A comprehensive investigation of the anion inhibition profile of a ß-carbonic anhydrase from Acinetobacter baumannii for crafting innovative antimicrobial treatments.

This study refers to the intricate world of Acinetobacter baumannii, a resilient pathogenic bacterium notorious for its propensity at antibiotic resistance in nosocomial infections. Expanding upon previous findings that emphasised the bifunctional enzyme PaaY, revealing unexpected γ-carbonic anhydrase (CA) activity, our research focuses on a different class of CA identified within the A. baumannii genome, the ß-CA, designated as 𝛽-AbauCA (also indicated as CanB), which plays a crucial role in the resistance mechanism mediated by AmpC beta-lactamase. Here, we cloned, expressed, and purified the recombinant 𝛽-AbauCA, unveiling its distinctive kinetic properties and inhibition profile with inorganic anions (classical CA inhibitors). The exploration of 𝛽-AbauCA not only enhances our understanding of the CA repertoire of A. baumannii but also establishes a foundation for targeted therapeutic interventions against this resilient pathogen, promising advancements in combating its adaptability and antibiotic resistance.

Inside-out, antimicrobial resistance mediated by efflux pumps in clinical strains of Acinetobacter baumannii isolated from burn wound infections.

Acinetobacter baumannii belongs to the ESKAPE group. It is classified as a critical priority group by the World Health Organization and a global concern on account of its capacity to acquire and develop resistance mechanisms to multiple antibiotics. Data from the United States indicates 500 deaths annually. Resistance mechanisms of this bacterium include enzymatic pathways such as ß-lactamases, carbapenemases, and aminoglycoside-modifying enzymes, decreased permeability, and overexpression of efflux pumps. A. baumannii has been demonstrated to possess efflux pumps, which are classified as members of the MATE family, RND and MFS superfamilies, and SMR transporters. The aim of our work was to assess the distribution of efflux pumps and their regulatory gene expression in clinical strains of A. baumannii isolated from burned patients. METHODS: From the Clinical Microbiology Laboratory at the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra collection in Mexico, 199 strains were selected. Antibiotics susceptibilities were performed by broth microdilutions to determine minimal inhibitory concentrations. Phenotypic assays with efflux pump inhibitors were conducted using carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and phenylalanine-arginine ß-naphthylamide (PAßN) in conjunction with amikacin, ceftazidime, imipenem, meropenem and levofloxacin. A search was conducted for structural genes that are linked to efflux pumps, and the relative expression of the adeR, adeS, and adeL genes was analyzed. RESULTS: Among a total of 199 strains, 186 exhibited multidrug resistance (MDR). Fluoroquinolones demonstrated the highest resistance rates, while minocycline and amikacin displayed comparatively reduced resistance rates (1.5 and 28.1, respectively). The efflux activity of fluorquinolones exhibited the highest phenotypic detection (from 85 to 100%), while IMP demonstrated the lowest activity of 27% with PAßN and 43.3% with CCCP. Overexpression was observed in adeS and adeL, with adeR exhibiting overexpression. Concluding that clinical strains of A. baumannii from our institution exhibited efflux pumps as one of the resistance mechanisms.

Molecular epidemiology of Acinetobacter baumannii during COVID-19 at a hospital in northern China.

BACKGROUND: The wide spread of carbapenem-resistance clones of Acinetobacter baumannii has made it a global public problem. Some studies have shown that the prevalence of Acinetobacter baumannii clones can change over time. However, few studies with respect to the change of epidemiological clones in Acinetobacter baumannii during Corona Virus Disease 2019 (COVID-19) were reported. This study aims to investigate the molecular epidemiology and resistance mechanisms of Acinetobacter baumannii during COVID-19. RESULTS: A total of 95 non-replicated Acinetobacter baumannii isolates were enrolled in this study, of which 60.0% (n = 57) were identified as carbapenem-resistant Acinetobacter baumannii (CRAB). The positive rate of the blaOXA-23 gene in CRAB isolates was 100%. A total of 28 Oxford sequence types (STs) were identified, of which the most prevalent STs were ST540 (n = 13, 13.7%), ST469 (n = 13, 13.7%), ST373 (n = 8, 8.4%), ST938 (n = 7, 7.4%) and ST208 (n = 6, 6.3%). Differently, the most widespread clone of Acinetobacter baumannii in China during COVID-19 was ST208 (22.1%). Further study of multidrug-resistant ST540 showed that all of them were carrying blaOXA-23, blaOXA-66, blaADC-25 and blaTEM-1D, simultaneously, and first detected Tn2009 in ST540. The blaOXA-23 gene was located on transposons Tn2006 or Tn2009. In addition, the ST540 strain also contains a drug-resistant plasmid with msr(E), armA, sul1 and mph(E) genes. CONCLUSION: The prevalent clones of Acinetobacter baumannii in our organization have changed during COVID-19, which was different from that of China. ST540 strains which carried multiple drug-resistant mobile elements was spreading, indicating that it is essential to strengthen the molecular epidemiology of Acinetobacter baumannii.

Unveiling the Secrets of Acinetobacter baumannii: Resistance, Current Treatments, and Future Innovations.

Acinetobacter baumannii represents a significant concern in nosocomial settings, particularly in critically ill patients who are forced to remain in hospital for extended periods. The challenge of managing and preventing this organism is further compounded by its increasing ability to develop resistance due to its extraordinary genomic plasticity, particularly in response to adverse environmental conditions. Its recognition as a significant public health risk has provided a significant impetus for the identification of new therapeutic approaches and infection control strategies. Indeed, currently used antimicrobial agents are gradually losing their efficacy, neutralized by newer and newer mechanisms of bacterial resistance, especially to carbapenem antibiotics. A deep understanding of the underlying molecular mechanisms is urgently needed to shed light on the properties that allow A. baumannii enormous resilience against standard therapies. Among the most promising alternatives under investigation are the combination sulbactam/durlobactam, cefepime/zidebactam, imipenem/funobactam, xeruborbactam, and the newest molecules such as novel polymyxins or zosurabalpin. Furthermore, the potential of phage therapy, as well as deep learning and artificial intelligence, offer a complementary approach that could be particularly useful in cases where traditional strategies fail. The fight against A. baumannii is not confined to the microcosm of microbiological research or hospital wards; instead, it is a broader public health dilemma that demands a coordinated, global response.

The Microbiological Characteristics of Acinetobacter Baumannii Associated With Early Mortality in Patients With Bloodstream Infection.

Background: Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM. Methods: Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5-30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model. Results: Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS+, and bauA- isolates showed higher virulence than non-ST191, bfmS-, and bauA+ isolates, respectively. Conclusions: ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management.

Evaluation of antibiotic resistance changes in Acinetobacter baumannii in the era of COVID-19 in Northern Iran.

Background and Objectives: During the coronavirus pandemic, the overuse of antibiotics to reduce coinfections and mortality may be contributing to the rise of antimicrobial resistance. In this study, we aim to investigate the antibiotic resistance changes of Acinetobacter baumannii post-COVID-19 pandemic in Northern Iran. Materials and Methods: The current study is a cross-sectional study. Between 2022 and 2023, 2190 clinical samples were collected from patients with healthcare-associated infections (HAIs) at four hospitals in Sari, which served as corona centers after the COVID-19 pandemic. Antimicrobial sensitivity was determined using standard broth macro-dilution, and resistance genes were detected using multiplex PCR. Results: Based on the results co-amoxiclav had a resistance rate of 100%, while piperacillin/tazobactam showed the least resistance rate of 29.82%. In terms of GM MIC values, colistin was the most potent against multi-drug resistant isolates. The frequency of bla OXA-51 , ampC, aphA6, and bla NDM genes were 100%, 99.12%, 90.35%, and 69.30% respectively. Conclusion: Our study revealed high multi-drug resistance rates. Piperacillin/tazobactam recommended for treating multi-drug resistant Acinetobacter baumannii infections in Northern Iran.

Secondary bacterial infections in post-COVID-19 mucormycosis cases: a retrospective study at Imam Khomeini Hospital Complex, March 2020-April 2021.

Background and Objectives: To explore the prevalence and characteristics of secondary bacterial infections among patients suffering from mucormycosis following COVID-19 infection. Materials and Methods: We conducted a cross-sectional, retrospective analysis from March 2020 to April 2022 at Imam Khomeini Hospital Complex in Tehran. The study included patients with histopathologically confirmed mucormycosis and documented secondary bacterial infections. We extracted and analyzed data from hospital records using SPSS software, version 26. Results: The study comprised 27 patients, with a predominance of females (70.4%) and an average age of 56 years. The majority of these patients (63%) had pre-existing diabetes mellitus. The severity of their COVID-19 infections varied. Treatment regimens included immunosuppressive drugs and antibiotics. Rhinocerebral mucormycosis was the most common form observed. The predominant secondary infections involved the urinary tract, respiratory system, bloodstream (bacteremia), and soft tissues, with resistant strains of Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae being the most frequently identified microorganisms. Notably, cases of bacteremia and pneumonia exhibited a higher mortality rate. Ultimately, 55.6% of patients were discharged, while 44.4% succumbed to their infections. Conclusion: Patients recovering from COVID-19 with mucormycosis are significantly susceptible to secondary bacterial infections, particularly those with diabetes mellitus or those undergoing immunosuppressive therapy. Such infections compound the morbidity and mortality risks in this vulnerable patient cohort.