The context of blaOXA-23 gene in Iraqi carbapenem-resistant Acinetobacter baumannii isolates belonging to global clone 1 and global clone 2.

BACKGROUND AND OBJECTIVES: Of the genes conferring resistance to carbapenems in Acinetobacter baumannii, the blaOXA-23 gene is the most widely found across the world. The gene carrying blaOXA-23 transposons in A. baumannii isolates of global clones GC1 and GC2 is found worldwide. Here, we examined whether transposons play a role in the dissemination of the blaOXA-23 in globally distributed clones, GC1 and GC2 A. baumannii isolates from Iraq. MATERIALS AND METHODS: The 119 non-repetitive A. baumannii isolates including 94 recovered from clinical specimens and 25 isolates from hospital environment between September 2021 and April 2022 from different medical centers located at various regions in Baghdad, Iraq. The global clones (GC) and the genes encoding carbapenem resistance, including blaOXA-23, blaOXA-24, and blaOXA-58 were identified using multiplex PCR assays. Antibiotic susceptibility testing was performed by the Kirby-Bauer disk diffusion susceptibility method. The transposons carrying blaOXA-23 were examined using PCR mapping. In cases when carbapenem susceptible A. baumannii isolates were found, they were subjected to E test, full length sequencing of blaOXA-Ab (blaOXA-51-like) and Institut Pasteur multi-locus sequence typing scheme. RESULTS: All but two isolates (92 clinical and 25 environmental) were identified carbapenem-resistant A. baumannii (CRAB). Of 117 CRAB isolates, 20 belong to GC1, 19 contained blaOXA-23; of them, 17 isolates harbored the blaOXA-23 located on Tn2006. Among the 46 CRAB belonging to GC2, 39 contained blaOXA-23; of them, 34 carried the blaOXA-23 located on Tn2006. The remaining GC1 and GC2 isolates, one GC1 as well as one GC2 isolate, were susceptible to imipenem, doripenem, and meropenem and considered carbapenem-susceptible A. baumannii (CSAB). Full-length sequencing of the blaOXA-Ab and MLST for the two CSAB isolates belonging to GC1 and GC2 confirmed that the GC1 isolate belongs to ST 623 and contained an allele that encodes an blaOXA-69 variant of the blaOXA-Ab while the GC2 belong to ST2 and carried an blaOXA-66 variant. CONCLUSION: This study provides evidence for the dissemination of blaOXA-23 on the Tn2006 in CRAB isolates in Baghdad, Iraq. It appears that this transposon is widespread in GC1 and 2 isolates as in the other parts of the world. Interestingly, one GC1 and one GC2 isolate from Iraq were found to be susceptible to carbapenem while the isolates belonging to GC1 and GC2 have so far rarely been found to be susceptible to carbapenem globally.

Cost-effectiveness analysis of polymyxin B versus colistin for treating patients with carbapenem-resistant gram-negative bacterial infections.

The prevalence of carbapenem-resistant gram-negative bacterial (CRGNB) infection is continuously increasing, and polymyxin B and colistin are considered last-resort drugs. This study compared the cost-effectiveness of polymyxin B with that of colistin for the treatment of intensive care unit patients with CRGNB infection from the Chinese healthcare perspective. A decision-analytic Markov model was constructed to assess the cost-effectiveness of polymyxin B compared with colistin over a period of 5 years using evidence from phase trials and other publicly available studies. The model was developed in Treeage Pro 2022 and comprises a decision tree depicting initial hospitalization and a Markov model with four states projecting long-term health and economic impacts following discharge. Uncertainty was tested with one-way sensitivity analyses and probabilistic sensitivity analyses. The quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratio (ICER) were estimated at willingness-to-pay (WTP) thresholds of $12,674 to $38,024 per QALY. According to the base analyses, the cost incurred by patients receiving colistin treatment was $12,244.77, leading to a gain of 1.35 QALYs. In contrast, patients treated with polymyxin B had a lower cost of $7,306.71 but yielded 1.07 QALYs. The ICRE of colistin was $18032.25/QALY. At a $12,674/QALY threshold, the results were sensitive to several variables, including the probability of cure with polymyxin B, the cost of drugs, the utility of discharge to home, the utility of discharge to long-term care, and the cost of nephrotoxicity with renal replacement therapy. After all model inputs varied across a wide range of reasonable values, only the probability of being cured with polymyxin B resulted in an ICER above the $38,024/QALY threshold. According to the probabilistic sensitivity analyses, colistin was the optimal strategy in 38.2% and 62.8% of the simulations, at $12,674/QALY and $38,024/QALY, respectively. Our study findings suggest that, when considering the Chinese healthcare perspective, colistin is likely to be more cost-effective than polymyxin B for patients with CRGNB infection, especially when the WTP threshold is set at one-time the per capita GDP. However, as the WTP threshold increases from one to three times the per capita GDP, the cost-effectiveness acceptability of colistin improves, increasing from 38.2 to 62.8%.

Virulence plasmid with IroBCDN deletion promoted cross-regional transmission of ST11-KL64 carbapenem-resistant hypervirulent Klebsiella pneumoniae in central China.

BACKGROUND: Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) caused infections of high mortality and brought a serious impact on public health. This study aims to evaluate the epidemiology, resistance and virulence characteristics of CR-hvKP and to identify potential drivers of cross-regional transmission in different regions of China, in order to provide a basis for developing targeted prevention measures. METHODS: Clinical K. pneumoniae strains were collected from Jiujiang and Nanchang in Jiangxi province between November 2021 to June 2022. Clinical data of patients (age, sex, source of infection, and diagnosis) were also gathered. We characterized these strains for their genetic relatedness using PFGE, antimicrobial and virulence plasmid structures using whole-genome sequencing, and toxicity using Galleria mellonella infection model. RESULTS: Among 609 strains, 45 (7.4%) CR-hvKP were identified, while the strains. isolated from Nanchang and Jiujiang accounted for 10.05% (36/358) and 3.59% (9/251). We observed that ST11-KL64 CR-hvKP had an overwhelming epidemic dominance in these two regions. Significant genetic diversity was identified among all ST11-KL64 CR-hvKP cross-regional transmission between Nanchang and Jiujiang and this diversity served as the primary driver of the dissemination of clonal groups. Virulence genes profile revealed that ST11-KL64 CR-hvKP might harbour incomplete pLVPK-like plasmids and primarily evolved from CRKP by acquiring the hypervirulence plasmid. We found the predominance of truncated-IncFIB/IncHI1B type virulence plasmids with a 25 kb fragment deletion that encoded iroBCDN clusters. CONCLUSION: ST11-KL64 is the most cross-regional prevalent type CR-hvKPs in Jiangxi province, which mainly evolved from CRKPs by acquiring a truncated-IncHI1B/IncFIB virulence plasmid with the deletion of iroBCDN. Stricter surveillance and control measures are urgently needed to prevent the epidemic transmission of ST11-KL64 CR-hvKP.

Clinical experience with ceftazidime/avibactam for the treatment of extensively drug-resistant or pandrug-resistant Klebsiella pneumoniae in neonates and children.

PURPOSE: Klebsiella pneumoniae is a significant cause of healthcare-associated infections, resulting in high morbidity and mortality rates due to limited treatment options. In this study, we aimed to evaluate the treatment outcomes and the safety of Ceftazidime-avibactam in infections caused by extensively drug-resistant or pandrug-resistant Klebsiella pneumoniae in pediatric patients. METHODS: This study included pediatric patients who received ceftazidime-avibactam treatment due to extensively drug-resistant or pandrug-resistant Klebsiella pneumoniae infections, monitored in the pediatric intensive care, neonatal intensive care, and pediatric wards of Cukurova University Faculty of Medicine between 2022 and 2023. Patients' microbiological responses, clinical responses, medication side effects, and 30-day survival rates were evaluated. RESULTS: Eleven pediatric patients were included in the study, of whom nine were male (81.8%). The median age at the initiation of ceftazidime-avibactam treatment was 15 months (range: 14 days-183 months). Sepsis was diagnosed in 9 patients (81.8%). Two premature infants (27 and 35 weeks) were admitted to the neonatal ICU. Regarding the Klebsiella pneumoniae strains, 10 (91%) were extensively drug-resistant (XDR), and 1 (9%) was pandrug-resistant (PDR). Eight strains (72.7%) were carbapenem-resistant, and 9 (81.8%) were colistin-resistant. Microbiological response was noted in 8 patients (72.7%), clinical response was evident in 6 patients (54.5%). The 30-day survival rate was 54.5%, with six patients surviving. CONCLUSION: In our study, ceftazidime-avibactam has been identified as a significant treatment option for resistant Klebsiella pneumoniae infection in critically ill children and premature infants with sepsis and organ failure, and it has been found to be well tolerated.

Navigating the Current Treatment Landscape of Metallo-ß-Lactamase-Producing Gram-Negative Infections: What are the Limitations?

The spread of carbapenemase-producing gram-negative pathogens, especially those producing metallo-ß-lactamases (MBLs), has become a major health concern. MBLs are molecularly the most diverse carbapenemases, produced by a wide spectrum of gram-negative organisms, including the Enterobacterales, Pseudomonas spp., Acinetobacter baumannii, and Stenotrophomonas maltophilia, and can hydrolyze most ß-lactams using metal ion cofactors in their active sites. Over the years, the prevalence of MBL-carrying isolates has increased globally, particularly in Asia. MBL infections are associated with adverse clinical outcomes including longer length of hospital stay, ICU admission, and increased mortality across the globe. The optimal treatment for MBL infections not only depends on the pathogen but also on the underlying resistance mechanisms. Currently, there are only few drugs or drug combinations that can efficiently offset MBL-mediated resistance, which makes the treatment of MBL infections challenging. The rising concern of MBLs along with the limited treatment options has led to the need and development of drugs that are specifically targeted towards MBLs. This review discusses the prevalence of MBLs, their clinical impact, and the current treatment options for MBL infections and their limitations. Furthermore, this review will discuss agents currently in the pipeline for treatment of MBL infections.

Design, synthesis, and bioactivity investigation of novel cyclic lipopeptide antibiotics targeting top-priority multidrug-resistant gram-negative bacteria.

OBJECTIVES: Polymyxins are the last-line therapy for top-priority multidrug-resistant (MDR) gram-negative bacteria. However, polymyxin nephrotoxicity impedes its clinical application. This study aimed to design, synthesize, and identify a novel and promising polymyxin derivative with high efficacy and low toxicity. METHODS: To design polymyxin derivatives, we reduced the hydrophobicity of the two hydrophobic domains (fatty acyl chain and D-Phe6-L-Leu7) and modified the positive charged L-2,4-diaminobutyric acid (Dab) residues. Twenty-five derivatives were synthesized, and their antibacterial activities in vitro and renal cytotoxicities were determined. The nephrotoxicity and pharmacokinetic parameters of compound 12 were examined in rats. Antibacterial efficacy in vivo was evaluated using a mouse systemic infection model. Surface plasmon resonance analysis, compound 12-rifampicin combination therapy, and scanning electron microscopy were used to study the mechanism of action of compound 12. RESULTS: This research found a new compound, identified as compound 12, which showed similar or increased antibacterial activity against all tested sensitive and carbapenem-resistant gram-negative bacteria. It exhibited reduced renal cytotoxicity and nephrotoxicity, a favorable pharmacokinetic profile, and maintained or improved antibacterial efficacy in vivo. Importantly, its anti-Pseudomonas aeruginosa activity significantly improved. Compound 12, when combined with rifampicin, enhanced the activity of rifampin against gram-negative bacteria. Compound 12 also showed a high affinity for lipopolysaccharide and disrupted cell membrane integrity. CONCLUSION: Reducing the hydrophobicity of the two domains reduced renal cytotoxicity and nephrotoxicity. Shortening the side chain of Dab3 by one carbon maintained or increased its antibacterial activity both in vitro and in vivo. Furthermore, only the length of the side chain of Dab9 could be shortened by one carbon among the Dab1,5 and Dab8,9 residues. The bactericidal effects of compound 12 were related to the disruption of cell membrane integrity. Compound 12 may be a promising candidate for combating sensitive and carbapenem-resistant gram-negative bacterial infections, especially Pseudomonas aeruginosa.

Molecular Detection of Carbapenemases in Acinetobacter baumannii Strains of Portugal and Association With Sequence Types, Capsular Types, and Virulence.

PURPOSE: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important nosocomial pathogen. The capsular type (K-type) is considered a major virulence factor, contributing to the evasion of host defenses. The global spread and dissemination dynamics between K-types, sequence types (ST), antibiotic resistance genes, and virulence factors remain largely unknown in Portugal. METHODS: A collection of 96 CRAB clinical samples collected between 2005 and 2019 in the northern region of Portugal were tested for antimicrobial susceptibility profile and screened by polymerase chain reaction for resistance genetic determinants. A subset of 26 representative isolates was subjected to whole-genome sequencing to assess K types, ST types, and genomic relatedness. The pathogenicity of distinct K-types was also tested using Galleria mellonella model. FINDINGS: For the 96 CRAB isolates analyzed, high antimicrobial resistance (>90%) was observed to the carbapenems, fluoroquinolones, and miscellaneous agents. Greater antimicrobial susceptibility (∼30%-57%) was observed for aminoglycosides, particularly tobramycin, and amikacin. Genotypically, 75 strains (78.5%) carried blaOXA-23-like, 18 strains (18.8%) carried blaIMP-like, and 11 strains (14.9%) carried blaOXA-40-like carbapenem resistance genes, respectively. Associations between OXA and ST/capsular locus (KL) types were observed over the years (eg, OXA-40-like/ST46Past/KL120 and OXA-23-like/ST2Past/KL2). ST2Past of clonal complex II was present in most strains, a dominant drug-resistant lineage in the United States and Europe. KL7 was also the most prevalent KL-type (38.5%), followed by KL2 (34.6%), KL120 (23.1%), and KL9 (3.8%). Virulence assessment for different K-types in a Galleria mellonella model revealed a significantly increased virulence for KL120 when compared with KL7, KL9, and KL2. IMPLICATIONS: There are specific CRAB serotypes circulating in Portugal, accounting by the low diversity of acquired carbapenemase genes (OXA-23-like and OXA-40-like), ST types (ST2 and ST46) and KL types (KL2, KL7, KL9, and KL120) identified. The high prevalent of ST2, especially when associated with KL2 and blaOXA-23-like, suggest that antibiotic resistance has been driven by clonal expansion of clonal complex II. Such findings provide useful information on the diversity of multidrug-resistant bacterium that might be relevant for antibacterial interventions.

High frequency of acquired virulence factors in carbapenemase-producing Klebsiella pneumoniae isolates from a large German university hospital, 2013-2021.

Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) isolates are a public health concern as they can cause severe hospital-acquired infections that are difficult to treat. It has recently been shown that CP-Kp can take up virulence factors from hypervirulent K. pneumoniae lineages. In this study, 109 clinical CP-Kp isolates from the University Hospital Cologne were examined for the presence of acquired virulence factors using whole-genome sequencing and phenotypic tests, and results were linked to clinical data. The virulence factor iuc was present in 18/109 of the CP-Kp isolates. Other acquired virulence factors, such as ybt, cbt, iro, rmpA/rmpA2, peg-344, and hypervirulence-associated capsule types were detected in various combinations among these isolates. The iuc-positive isolates produced OXA-232 (n = 7), OXA-48 (n = 6), OXA-48+NDM (n = 3), NDM, and KPC (each n = 1), and 7/18 isolates were resistant to ceftazidime-avibactam, colistin, and/or cefiderocol. Four isolates carried hybrid plasmids that harbored acquired virulence factors alongside the carbapenemase genes blaNDM-1/5 or blaOXA-48. In 15/18 patients, iuc-positive CP-Kp were isolated from a clinically manifest infection site. Among these, four patients had osteomyelitis, and four patients died from pneumonia with OXA-232-producing ST231 isolates, three of them as part of an outbreak. In conclusion, acquired virulence factors are frequently detected in various combinations in carbapenemase-producing K. pneumoniae isolates in Germany, warranting continuous monitoring of infections caused by these strains.

Potentially effective antimicrobial treatment for pneumonia caused by isolates of carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii complex species: what can we expect in the future?

INTRODUCTION: Acinetobacter baumannii complex (Abc) is currently a significant cause of difficult-to-treat pneumonia. Due to the high prevalence rates of carbapenem- and extensively drug-resistant (CR, XDR) phenotypes, limited antibiotic options are available for the effective treatment of pneumonia caused by CR/XDR-Abc. AREAS COVERED: In vitro susceptibility data, relevant pharmacokinetic profiles (especially the penetration ratios from plasma into epithelial-lining fluid), and pharmacodynamic indices of key antibiotics against CR/XDR-Abc are reviewed. EXPERT OPINION: Doubling the routine intravenous maintenance dosages of conventional tigecycline (100 mg every 12 h) and minocycline (200 mg every 12 h) might be recommended for the effective treatment of pneumonia caused by CR/XDR-Abc. Nebulized polymyxin E, novel parenteral rifabutin BV100, and new polymyxin derivatives (SPR206, MRX-8, and QPX9003) could be considered supplementary combination options with other antibiotic classes. Regarding other novel antibiotics, the potency of sulbactam-durlobactam (1 g/1 g infused over 3 h every 6 h intravenously) combined with imipenem-cilastatin, and the ß-lactamase inhibitor xeruborbactam, is promising. Continuous infusion of full-dose cefiderocol is likely an effective treatment regimen for CR/XDR-Abc pneumonia. Zosurabalpin exhibits potent anti-CR/XDR-Abc activity in vitro, but its practical use in clinical therapy remains to be evaluated. The clinical application of antimicrobial peptides and bacteriophages requires validation.

Ceftazidime/avibactam combined with colistimethate sodium successfully cures carbapenem-resistant Pseudomonas aeruginosa-induced brain abscess in a child post-craniotomy: a case report.

The treatment of brain abscess induced by carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a clinical challenge around the world. Apart from novel ß-lactam/ß-lactamase inhibitors and polymyxins, there are few sufficiently powerful antibiotics that are effective against CRPA-induced infections. Considering the blood-brain barrier factor, there are even fewer drugs that can be used to treat intracranial CRPA-induced infections. In this article, we reported a case of CRPA-induced brain abscess that was successfully treated with intravenous ceftazidime/avibactam and intrathecal colistimethate sodium in a child after intracranial tumor resection.

Nosocomial carbapenem-drug resistant Acinetobacter baumannii, related factors and clinical outcomes in Northeast Iran.

BACKGROUND AND OBJECTIVES: Nosocomial infections, including drug-resistant Acinetobacter baumannii infections, continue to impact the health of hospitalized patients. This study sought to determine the prevalence of these infections and assess the associated risk factors and clinical outcomes in Gorgan, Iran. METHODS: A retrospective cross-sectional study was conducted on 143 infected patients with Acinetobacter baumannii in two educational hospitals in Gorgan city, Iran between 2016 and 2018. Patient information including age, gender, reason and duration of hospitalization, background of diseases, type of sample culture, symptoms, laboratory findings, prescribed antibiotics, and antibiogram were collected and analyzed. The Logistic regression and survival statistical methods were used by software of SPSS 26. RESULTS: A total of 37 patients (25.87%) died during hospitalization. The less than one year and 45-65 years age groups demonstrated more deaths (29.7%; p-value < 0.001). Being single (not being married) was found to be a risk factor in increasing the chance of death among patients (OR = 2.154, 95% CI: 1.02-4.53; p = 0.048). Hospitalization in intensive care units (ICUs) was a risk factor for the death of patients (OR = 4.655, 95% CI: 7.6-83.2). The resistance to carbapenems was reported to be an important risk factor for the death of patients. CONCLUSIONS: Acinetobacter baumannii infections, particularly those resistant to carbapenems, are a significant risk for patients in ICUs and can lead to higher mortality rates.

Mobile Genetic Elements Contributing to Horizontal Gene Transfer of blaNDM among Escherichia coli in the community setting.

OBJECTIVE: To investigate the distribution of carbapenem-resistant Enterobacterales (CRE) in the community and to describe the genomic characteristics. METHODS: CRE screened from fecal samples in healthy people at the health examination center of a tertiary hospital in China underwent Whole genome sequencing (WGS) to analyze genotypic characteristics of CRE. The flanking DNA sequence of blaNDM-5 and mcr1.1 genes were analyzed by Gcluster software. RESULTS: A total of 7187 fecal samples were screened, and CRE carriage was detected in 0.4% of the sampled population. In total, 30 Escherichia coli, one Citrobacter freundii and one Klebsiella aerogene were screened. The 30 carbapenem-resistant Escherichia coli (CREC) isolates displayed slight resistance to amikacin (13.3%) and aztreonam (20.0%). All the CRE isolates contained blaNDM, and blaNDM-5 (84.4%) was the most common one. B1 (n=11) and A (n=7) were predominant phylogroups. Furthermore, 34 distinct plasmid replicons, 67 different VFs, 22 distinct STs, 17 different FimH types, 26 O:H serotypes as well as 74 MGEs including 61 insertion sequences and 13 transposons were identified. The flanking DNA sequence analysis of blaNDM-5 and mcr1.1 genes indicates the key role of horizontal transfer of blaNDM-5 in the CRE development evidenced by diverse STs and phylogenetic tree. CONCLUSION: E. coli was the most predominant CRE isolates in community setting, and blaNDM (blaNDM-5) was the main CHßL encoding genes. The high prevalence of ARGs was associated with high resistance to commonly used antimicrobials. Besides, the genetic diversity of these isolates suggested the key role of blaNDM horizontal transfer in the CRE development. Thus, active screening of blaNDM in communities is particularly important for the prevention and control of CRE.

Effectiveness of combination therapy with intrathecal or intraventricular administration of polymyxin B for hospital-acquired central nervous system infections caused by carbapenem-resistant Acinetobacter baumannii: a retrospective study.

OBJECTIVES: To evaluate the therapeutic regimen, efficacy and safety of intrathecal or intraventricular (ITH/IVT) administration of polymyxin B for hospital-acquired central nervous system (CNS) infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: A retrospective study was performed on patients with CNS infections caused by CRAB treated with ITH/IVT combination therapy. The primary study outcome was the clinical efficacy after treatment. Secondary outcomes were bacterial clearance rate and safety of therapy. RESULTS: In total, 35 patients who received ITH (13[37.1%]) or IVT (22[62.9%]) polymyxin B as combination therapy were included. The median duration of ITH/IVT polymyxin B therapy was 9 days (interquartile ranges, 7-11). The overall clinical cure and bacterial clearance rate was 77.1% and 85.7%, respectively. No adverse effects deemed related with ITH/IVT polymyxin B were recorded. Clinical failure was independently associated with the initial Acute Physiology and Chronic Health Evaluation II (≥ 15) (odds ratio [OR], 1.24; 95% confidence interval [CI]: 1.05-1.42; P = 0.038) and Glasgow Coma Scale scores (≤ 8) (OR, 0.69; 95% CI: 0.49-0.88; P = 0.029). Early administration (within 4 days) of ITH/IVT polymyxin B therapy can support significantly higher clinical cure rate (OR, 0.65; 95% CI: 0.49-1.12; P < 0.001), and potentially reduce the length of treatment and the adverse effects. CONCLUSIONS: ITH/IVT administration of polymyxin B is a valid alternative for the treatment of CNS infections caused by CRAB. Early use of ITH/IVT polymyxin B can lead to higher clinical success.

Ceftazidime-avibactam: Combination therapy versus monotherapy in the challenge of pneumonia caused by carbapenem-resistant Klebsiella pneumoniae.

This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime-avibactam (CZA) alone or in combination with other antibiotics. From January 2020 to December 2023, we retrospectively analyzed CRKP-related pneumonia patients treated in two Chinese tertiary hospitals. Mortality was measured at 14 and 30 days as the primary outcome. Secondary outcomes included the 14-day microbiological cure rate and the 14-day clinical cure rate. Factors contributing to clinical failure were evaluated via both univariate analysis and multivariate logistic regression. To account for confounding factors, propensity score matching (PSM) was utilized. Among the 195 patients with CRKP infections, 103 (52.8 %) received CZA combination therapy, and 92 (47.2 %) patients received CZA monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % (P = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % (P = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P = 0.066). Even after using PSM, the group treated with the CZA combination continued to had a lower mortality rate at 14 days (5.9 % vs. 17.6 %, P = 0.039). The 14-day clinical cure rate for the combination therapy group was 63.2 %, and the 14-day microbial cure rate was 77.9 %. Both of these statistics were notably greater than those observed in the monotherapy group. Furthermore, the multivariate logistic regression model indicated a significant link between combination therapy and a decrease in clinical failure. Carbapenems were noted to be the most effective class of concomitant agents. Our findings indicate that patients with pneumonia due to CRKP benefit from combination treatment of CZA rather than monotherapy; administering carbapenem in combination with CZA in the early stages could provide considerable survival benefits.

Molecular epidemiology, microbiological features and infection control strategies for carbapenem-resistant Acinetobacter baumannii in a German burn and plastic surgery center (2020-2022).

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) frequently causes both healthcare-associated infections and nosocomial outbreaks in burn medicine/plastic surgery and beyond. Owing to the high antibiotic resistance, infections are difficult to treat, and patient outcomes are often compromised. The environmental persistence capability of CRAB favors its transmission in hospitals. A comprehensive analysis and understanding of CRAB epidemiology and microbiology are essential for guiding management. METHODS: A three-year retrospective cohort study (2020-2022) was conducted in a German tertiary burn and plastic surgery center. In addition to epidemiological analyses, microbiological and molecular techniques, including whole-genome sequencing, were applied for the comprehensive examination of isolates from CRAB-positive patients. RESULTS: During the study period, eight CRAB cases were found, corresponding to an overall incidence of 0.2 CRAB cases per 100 cases and an incidence density of 0.35 CRAB cases per 1000 patient-days. Six cases (75%) were treated in the burn intensive care unit, and four cases (50%) acquired CRAB in the hospital. Molecular analyses comprising 74 isolates supported the epidemiologic assumption that hospital acquisitions occurred within two separate clusters. In one of these clusters, environmental CRAB contamination of anesthesia equipment may have enabled transmission. Furthermore, molecular diversity of CRAB isolates within patients was observed. CONCLUSIONS: CRAB can pose a challenge in terms of infection prevention and control, especially if cases are clustered in time and space on a ward. Our study demonstrates that high-resolution phylogenetic analysis of several bacterial isolates from single patients can greatly aid in understanding transmission chains and helps to take precision control measures.

Clinical outcomes and risk factors of Acinetobacter baumannii meningitis in pediatric patients at a tertiary hospital in China.

Objectives: To summarize the clinical characteristics, outcomes and identify risk factors of Acinetobacter baumannii (AB) meningitis in children. Methods: This was a single-center, retrospective study. Children hospitalized between January 2016 and December 2021 who were diagnosed with AB meningitis were included. The clinical characteristics and outcomes were reviewed. Risk factors were determined using univariate analyses (chi-square and Mann-Whitney U tests). Results: Seventeen patients were included; 15 cases were secondary to neurosurgery, and two were neonates with primary bacterial meningitis. Common symptoms included fever, convulsions and nervous system abnormalities. Cerebrospinal fluid (CSF) tests typically showed increased white blood cell counts dominated by neutrophils, reduced glucose levels and elevated protein levels. Ten patients were successfully treated (successful treatment [ST] group); seven had failed treatment (failed treatment [FT] group). Univariate analyses revealed that mechanical ventilation, routine white cell counts in the peripheral blood, procalcitonin, protein in the CSF, septic shock and carbapenem-resistant AB (CRAB) differed significantly between the groups. Conclusion: AB meningitis in children has a high mortality rate. FT was associated with mechanical ventilation, septic shock, CRAB, lower peripheral leukocyte counts, higher protein levels in the CSF and procalcitonin. Larger studies are needed to identify independent risk factors for adverse outcomes.

The effect of combinations of a glyphosate-based herbicide with various clinically used antibiotics on phenotypic traits of Gram-negative species from the ESKAPEE group.

The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-ß-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity.

Systematic Review and Meta-Analysis of Clinical Efficacy and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability to develop structural modifications and produce antibiotic-degrading enzymes, leading to high resistance levels, we sought to summarize the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MV) versus the best available therapy (BAT). Articles related to our objective were searched in the PubMed and Scopus databases inception to July 2024. To assess the quality of the studies, we used the Cochrane risk-of-bias tool, RoB2. The outcomes were pooled as a risk ratio (RR) and a 95% confidence interval (95%CI). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam). No significant difference in the clinical response rate was observed between MV and the comparators at the TOC (RR = 1.29, 95%CI [0.92, 1.80], p = 0.14) and EOT (RR = 1.66, 95%CI [0.58, 4.76], p = 0.34) visits. MV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], p = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], p = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], p = 0.03). MV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], p = 0.23). Additionally, MV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], p = 0.002). MV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], p = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], p = 0.09) as the comparators. In conclusion, MV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs.

Risk factors for infection after carbapenem-resistant Acinetobacter baumannii colonization.

PURPOSE: Predicting infection risk in carbapenem-resistant Acinetobacter baumannii (CRAB) colonized patients may help in improving timely appropriate antibiotic therapy. This study aims to explore risk factors for developing infections in hospitalized patients with previous CRAB colonization. METHODS: We performed an observational retrospective cohort study at ASST Sette Laghi-Varese Hospital between January 2020 and December 2022. All consecutive adult (> 18 years old) hospitalized patients with documented colonization by CRAB at any anatomical site or with CRAB infections preceded by CRAB colonization were included. Univariate and multivariate analyses were performed to investigate infection risk factors. RESULTS: Overall, 144 patients were included in the study: 104 colonized only and 40 infected patients. Colonization and infection rates significantly changed over the years (2020-2022, p < 0.001). The incidence of infections in CRAB carriers was 27.8% (40/144). Median time from colonization to infection was 4 days (IQR 1-8.5). Overall, inhospital mortality was 32.7% and 55.0% in colonized only and infected patients, respectively. At the multivariable logistic regression cardiovascular disease (OR 5.83, 95% CI 1.12-30.43, p = 0.037), COVID-19 (OR 3.72, 95% CI 1.16-11.91, p = 0.027) and intensive care unit (ICU) admission (OR 8.83, 95% CI 2.94-26.51, p < 0.001) were risk factors independently associated with cardiovascular disease CRAB infection after colonization. CONCLUSIONS: We observed an increased infection risk in patients colonized with CRAB with cardiovascular disease, COVID-19 and admitted in ICU setting. Additional evidence is needed to identify predictors of infection in colonized patients.

Innovative Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Pneumonia with Carrimycin: A Case Report.

Carbapenem-resistant Pseudomonas aeruginosa is a common multidrug-resistant bacterium encountered in clinical practice. This pathogen causes pneumonia, which is difficult to treat owing to the limited choice of antimicrobial drugs, resulting in a relatively high mortality rate. Carrimycin is a new macrolide antibiotic with broad-spectrum antibacterial and potential immunomodulatory effects. Herein, we report a case of severe pneumonia caused by carbapenem-resistant Pseudomonas aeruginosa that presented with septic shock and Acute Respiratory Distress Syndrome (ARDS). Initially, we used piperacillin-tazobactam and ceftazidime-avibactam but without satisfactory results. Finally, we administered carrimycin in combination with piperacillin-tazobactam; the patient's condition improved, and he was successfully weaned off the ventilator. Therefore, the combined use of carrimycin should be considered for patients infected with carbapenem-resistant Pseudomonas aeruginosa who do not respond to conventional anti-infection treatments.