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Abstract Background Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. Methods We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. Results We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. Conclusions Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.

Objective: To investigate the effectiveness of linezolid and vancomycin for the treatment of nosocomial infections in children under 12 years old. Data sources: This is a systematic review in which five randomized clinical trials about the effectiveness of linezolid and vancomycin, involving a total of 429 children with nosocomial infections, were evaluated. They were searched in scientific databases: PubMed, Bvs, and SciELO. Summary of findings: The main nosocomial infections that affected children were bacteremia, skin, and soft tissue infections followed by nosocomial pneumonia. Most infections were caused by Gram-positive bacteria, which all studies showed infections caused by Staphylococcus aureus, with methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci strains being isolated. Both linezolid and vancomycin showed high therapeutic efficacy against different types of nosocomial infections, ranging from 84.4% to 94% for linezolid and 76.9% to 90% for vancomycin. Patients receiving linezolid had lower rates of rash and red man syndrome compared to those receiving vancomycin. However, despite the adverse reactions, antimicrobials can be safely administered to children to treat nosocomial infections caused by resistant Gram-positive bacteria. Conclusion: Both linezolid and vancomycin showed good efficacy in the treatment of bacterial infections caused by resistant Gram-positive bacteria in hospitalized children. However, linezolid stands out regarding its pharmacological safety. Importantly, to strengthen this conclusion, further clinical trials are needed to provide additional evidence.

Background: Nosocomial infections are considered as the important parts of the treatment challenges in hospitals. The genus Artemisia is widely distributed in Iran. Their species produce antibacterial, antiviral, and antifungal compounds belonging to different groups including phenols, terpenoids, sterols and polyacetylenes. The purpose of the present study is to investigate the in vitro effects of different hydroethanolic extracts of Artemisia species against bacterial strains in nosocomial infection. Methods: 12 different extracts, including 50% and 70% hydroethanolic extracts were prepared from the aerial parts of Artemisia ciniformis, A. turanica, A. kopetdaghensis, A. khorasanica, A. vulgaris, and A. sieberi. The winterization of the extracts produced corresponding defatted extracts. The minimum inhibitory concentration (MIC) values of the extracts against the bacterial strains Staphylococcus aureus, Streptococcus pyogenes, Acinetobacter sp., Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococus epidermidis, Micrococcus luteus, Klebsiella pneumoniae and Escherichia coli were measured using the microdilution broth method. Total phenolic contents were determined by the Folin-Ciocalteu method. Results: Among the extracts analyzed in this experiment, the lowest MIC value was observed for the 50% hydroethanolic extract of A. turanica (0.25 mg/ml) against S. epidermidis. The largest range of bacterial sensitivity (6 strains) was related to the 50% hydroethanolic extracts of A. turanica (defatted and non-defatted) and A. kopetdaghensis (defatted). The growth of S. epidermidis was inhibited by all of the extracts. The highest total phenolic content and yield of extraction were recorded for 70% hydroethanolic extract of A. sieberi and 50% hydroethanolic extract of A. ciniformis, respectively. Conclusion: The 50% hydroethanolic extract of A. turanica was superior to the other extracts in terms of the in vitro antibacterial spectrum and selective potency. A. turanica and A. kopetdaghensis are probably suitable choices for further phytochemical and antibacterial investigations.

Xiaofeng Wang,1,2,* Shuo Li,3,* Da Huo,4,* Zhiyuan Zhu,1,2,* Wenlong Wang,1,2 Hongxia He,1,2 Qian Zhang,1,2 Jiantao Li,2,5 Xu Wang1,2 1Department of Pediatric Intensive Care Unit, National Center for Cardiovascular Disease and Fuwai Hospital, Beijing, People’s Republic of China; 2School of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Infection Control, Peking University First Hospital, Beijing, People’s Republic of China; 4Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 5Department of Infection Control, National Center for Cardiovascular Disease and Fuwai Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu Wang, Department of Pediatric Intensive Care Unit, National Center for Cardiovascular Disease and Fuwai Hospital, No. 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email fwpicu@163.comPurpose: Infection prevention and control (IPC) has a significant impact on the prognosis after pediatric cardiac surgery. This study aimed to provide surveillance data on the incidence and density of various infections during the COVID-19 epidemic and explore the influence of multi-drug resistant organisms (MDRO) on in-hospital prognosis after congenital heart disease surgery.Methods: This single-center retrospective study included pediatric patients who underwent cardiac surgery between 2021 and 2022. The results of the postoperative bacterial and fungal cultures and antimicrobial stewardship were collected. The demographic characteristics (age and weight), operation-related parameters (RACHS-1 grade, duration of cardiopulmonary bypass, and aortic cross clamp), and surgical outcomes (extracorporeal membrane oxygenation, delayed sternal closure, mortality, duration of mechanical ventilation, length of intensive care unit stay and hospital stay, and hospitalization costs) of MDRO and non-MDRO patients were compared.Results: A total of 4776 patients were included. There were 101 infectious culture results after the operation, with a nosocomial infection rate of 2.1%. There were 40 MDRO specimens from 36 patients, 50 non-MDRO specimens from 30 patients, and 11 fungal specimens from 10 patients. The incidence of pneumonia was 1.5%, with a ventilator-associated pneumonia incidence density of 7.2/1000 patient-days. The incidence of sepsis was 0.4%, with a catheter-related bloodstream infection incidence density of 0.24/ 1000 patient-days. The incidence density of catheter-associated tract infection was 0.45/ 1000 patient-days. The incidence of surgical site infection was 0.06%. The culture proportion before commencing antibiotics was 93% and the antibiotic consumption intensity was 30.7 DDD/100 bed-days. The length of intensive care unit stay in MDRO infection patients increased compared with that in non-MDRO infection patients, 30 (18,52) vs 17 (7,62) days, p=0.05).Conclusion: The IPC performance of Fuwai Hospital achieved satisfactory results. MDRO infection can lead to prolonged intensive care unit stay.Plain language summary: Developed countries have advanced infection prevention and control systems and comprehensive postoperative infection monitoring data for congenital heart disease. While developing countries have initiated efforts in infection prevention and control, global attention remains substantial. This study aimed to provide comprehensive infection surveillance data and identify possible implementation for further improvement in the National Center for Cardiovascular Diseases in China (Fuwai Hospital).This was a retrospective single-center study. We included pediatric patients who underwent cardiac surgery at a pediatric surgical center between 2021 and 2022, with an age limit of 14 years. Exclusion criteria included patients undergoing medical therapy, interventional therapy, or surgical therapy in other centers in Fuwai Hospital.This study, for the first time, reports the incidence of comprehensive healthcare-associated infection surveillance and targeted surveillance (encompassing device-associated infection, surgical site infection, and multi-drug resistant organisms) after pediatric cardiac surgery at the National Center for Cardiovascular Diseases in China. In addition, we report the data on antimicrobial stewardship. We compared the surgical outcome and hospitalization costs between patients with multi-drug resistant organism infection and those without multi-drug resistant organism infection and found that multi-drug resistant organism infection can lead to prolonged intensive care unit length of stay.The Fuwai Hospital achieved satisfactory infection prevention and control results. However, because China is a large developing country exhibiting notable variations in medical conditions across its diverse regions, prospective, multicenter, observational studies should be carried out for future research based on existing evidence.Keywords: nosocomial infections, pediatric cardiac surgery, multidrug-resistant organism, surgical outcomes

Serratia marcescens is an environmental gram-negative bacterium that causes invasive disease in rare cases. During 2020–2022, an outbreak of 21 invasive Serratia infections occurred in a prison in California, USA. Most (95%) patients had a history of recent injection drug use (IDU). We performed whole-genome sequencing and found isolates from 8 patients and 2 pieces of IDU equipment were closely related. We also identified social interactions among patients. We recovered S. marcescens from multiple environmental samples throughout the prison, including personal containers storing Cell Block 64 (CB64), a quaternary ammonium disinfectant solution. CB64 preparation and storage conditions were suboptimal for S. marcescens disinfection. The outbreak was likely caused by contaminated CB64 and propagated by shared IDU equipment and social connections. Ensuring appropriate preparation, storage, and availability of disinfectants and enacting interventions to counteract disease spread through IDU can reduce risks for invasive Serratia infections in California prisons.

In 2021, we identified a cluster of Elizabethkingia miricola cases in an intensive care unit in Spain. Because E. miricola is not considered a special surveillance agent in Spain, whole-genome sequencing was not performed. The bacterial source was not identified. All Elizabethkingia species should be listed as special surveillance bacteria.

High rates of resistance to antibiotics are associated with healthcare-related infections, thus demonstrating the urgent need for effective antimicrobials against these maladies. The present study aims to determine the chemical composition of essential oil (EO) from Clausena anisata leaves and evaluate their antibacterial activity against selected nosocomial bacteria. To this end, one kilogram (1 kg) of fresh leaves of C. anisata was washed and boiled with 500 mL of distilled water for 2−4 h using a Clevenger apparatus. The oil was then collected in an Erlenmeyer, dried using anhydrous sodium sulfate, bottled in a tinted glass bottle and refrigerated at 4 °C before analysis. Next, the as-prepared oil was analyzed using gas chromatography-mass spectrometry (GC-MS). The essential oil was further tested against a panel of selected nosocomial bacteria, including Staphylococcus and Klebsiella species, among others, by microdilution using a resazurin assay to determine the minimum inhibitory and minimum bactericidal concentrations (MICs and MBCs, respectively). As a result, 0.77% of EO was extracted from fresh leaves of C. anisata. The GC-MS analysis revealed that the as-prepared essential oil contained E-anethole (70.77%), methyl isoeugenol (13.85%), estragole (4.10%), γ-terpinene (3.33%), myrcene (2.82%) and sabinene (0.77%), with E-anethole being the major constituent. Twenty-two compounds were identified in the EO of C. anisata leaves through gas chromatography. Upon antibacterial testing against selected nosocomial pathogens, the E-anethole-rich essential oil exhibited MIC and MBC values ranging from 3.91 to 125 µg/mL and 7.81 to 125 µg/mL, respectively, indicative of a bactericidal orientation of the plant’s essential oil (MIC/MBC ratio < 4). This novel contribution highlights the scientific validation of the use of C. anisata leaves in the traditional treatment of various infectious diseases. However, toxicity and pharmacokinetic studies, mechanistic bases of the antibacterial action, and in vivo antibacterial experiments of the E-anethole-rich EO of C. anisata should be investigated to successfully use this plant in the treatment of infectious diseases.

Introduction: Carbapenemase-Producing Escherichia coli (CP-Eco) isolates, though less prevalent than other CP-Enterobacterales, have the capacity to rapidly disseminate antibiotic resistance genes (ARGs) and cause serious difficult-to-treat infections. The aim of this study is phenotypically and genotypically characterizing CP-Eco isolates collected from Spain to better understand their resistance mechanisms and population structure. Methods: Ninety representative isolates received from 2015 to 2020 from 25 provinces and 59 hospitals Spanish hospitals were included. Antibiotic susceptibility was determined according to EUCAST guidelines and wholegenome sequencing was performed. Antibiotic resistance and virulenceassociated genes, phylogeny and population structure, and carbapenemase genes-carrying plasmids were analyzed. Results and discussion: The 90 CP-Eco isolates were highly polyclonal, where the most prevalent was ST131, detected in 14 (15.6%) of the isolates. The carbapenemase genes detected were blaOXA-48 (45.6%), blaVIM-1 (23.3%), blaNDM-1 (7.8%), blaKPC-3 (6.7%), and blaNDM-5 (6.7%). Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). Four of the seven cefiderocol-resistant isolates belonged to ST167 and six harbored blaNDM. Five of the plazomicin-resistant isolates harbored rmt. IncL plasmids were the most frequent (45.7%) and eight of these harbored blaVIM-1. blaOXA-48 was found in IncF plasmids in eight isolates. Metallo-β-lactamases were more frequent in isolates with resistance to six or more antibiotic groups, with their genes often present on the same plasmid/integron. ST131 isolates were associated with sat and pap virulence genes. This study highlights the genetic versatility of CP-Eco and its potential to disseminate ARGs and cause community and nosocomial infections. [ABSTRACT FROM AUTHOR]

Background: Pancreatic stone protein (PSP) exhibits potential as a plasma biomarker for infection diagnosis and risk stratification in critically ill patients, but its significance in nosocomial infection and intensive care unit (ICU)-acquired bloodstream infection (BSI) remains unclear. This study explores the temporal responses of PSP in ICU-acquired BSI caused by different pathogens. Methods: From a large cohort of ICU patients, we selected episodes of ICU-acquired BSI caused by Gram-negative rods (GNRs), enterococci, or Candida species. Events were matched on length of ICU stay at infection onset, Severe Organ Failure Assessment (SOFA) score, presence of immune deficiency, and use of renal replacement therapy. PSP concentrations were measured at infection onset (T0) and at 24, 48 and 72 h prior to infection onset as defined by the first occurrence of a positive blood culture. Absolute and trend differences in PSP levels between pathogen groups were analysed using one-way analysis of variance. Sensitivity analyses were performed in events with a new or worsening systematic inflammatory response based on C-reactive protein, white cell count and fever. Results: We analysed 30 BSI cases per pathogen group. Median (IQR) BSI onset was on day 9 (6–12). Overall, PSP levels were high (381 (237–539) ng/ml), with 18% of values exceeding the assay's measurement range. Across all 90 BSI cases, there was no clear trend over time (median change 34 (− 75–189) ng/ml from T-72 to T0). PSP concentrations at infection onset were 406 (229–497), 350 (223–608), and 480 (327–965) ng/ml, for GNR, enterococci, and Candida species, respectively (p = 0.32). At every time point, absolute PSP levels and trends did not differ significantly between pathogens. PSP values at T0 correlated with SOFA scores. Eighteen (20%) of 90 BSI events did not exhibit a systemic inflammatory response, primarily in Candida species. No clear change in PSP concentration before BSI onset or between-group differences were found in sensitivity analyses of 72 cases. Conclusions: Against a background of overall (very) high plasma PSP levels in critically ill patients, we did not find clear temporal patterns or any pathogen-specific differences in PSP response in the days preceding onset of ICU-acquired BSI. [ABSTRACT FROM AUTHOR]

There are few studies comparing proportion, frequency, mortality and mortality rate following antimicrobial-resistant (AMR) infections between tertiary-care hospitals (TCHs) and secondary-care hospitals (SCHs) in low and middle-income countries (LMICs) to inform intervention strategies. The aim of this study is to demonstrate the utility of an offline tool to generate AMR reports and data for a secondary data analysis. We conducted a secondary-data analysis on a retrospective, multicentre data of hospitalised patients in Thailand. Routinely collected microbiology and hospital admission data of 2012 to 2015, from 15 TCHs and 34 SCHs were analysed using the AMASS v2.0 (www.amass.website). We then compared the burden of AMR bloodstream infections (BSI) between those TCHs and SCHs. Of 19,665 patients with AMR BSI caused by pathogens under evaluation, 10,858 (55.2%) and 8,807 (44.8%) were classified as community-origin and hospital-origin BSI, respectively. The burden of AMR BSI was considerably different between TCHs and SCHs, particularly of hospital-origin AMR BSI. The frequencies of hospital-origin AMR BSI per 100,000 patient-days at risk in TCHs were about twice that in SCHs for most pathogens under evaluation (for carbapenem-resistant Acinetobacter baumannii [CRAB]: 18.6 vs. 7.0, incidence rate ratio 2.77; 95%CI 1.72–4.43, p<0.001; for carbapenem-resistant Pseudomonas aeruginosa [CRPA]: 3.8 vs. 2.0, p = 0.0073; third-generation cephalosporin resistant Escherichia coli [3GCREC]: 12.1 vs. 7.0, p<0.001; third-generation cephalosporin resistant Klebsiella pneumoniae [3GCRKP]: 12.2 vs. 5.4, p<0.001; carbapenem-resistant K. pneumoniae [CRKP]: 1.6 vs. 0.7, p = 0.045; and methicillin-resistant Staphylococcus aureus [MRSA]: 5.1 vs. 2.5, p = 0.0091). All-cause in-hospital mortality (%) following hospital-origin AMR BSI was not significantly different between TCHs and SCHs (all p>0.20). Due to the higher frequencies, all-cause in-hospital mortality rates following hospital-origin AMR BSI per 100,000 patient-days at risk were considerably higher in TCHs for most pathogens (for CRAB: 10.2 vs. 3.6,mortality rate ratio 2.77; 95%CI 1.71 to 4.48, p<0.001; CRPA: 1.6 vs. 0.8; p = 0.020; 3GCREC: 4.0 vs. 2.4, p = 0.009; 3GCRKP, 4.0 vs. 1.8, p<0.001; CRKP: 0.8 vs. 0.3, p = 0.042; and MRSA: 2.3 vs. 1.1, p = 0.023). In conclusion, the burden of AMR infections in some LMICs might differ by hospital type and size. In those countries, activities and resources for antimicrobial stewardship and infection control programs might need to be tailored based on hospital setting. The frequency and in-hospital mortality rate of hospital-origin AMR BSI are important indicators and should be routinely measured to monitor the burden of AMR in every hospital with microbiology laboratories in LMICs. [ABSTRACT FROM AUTHOR]

Background: Avoiding excessive antibiotic treatment duration is a fundamental goal in antimicrobial stewardship. Manual collection of data is a time-consuming process, but a semi-automated approach for data extraction has been shown feasible for community-acquired infections (CAI). Extraction of data however may be more challenging in hospital-acquired infections (HAI). The aim of this study is to explore whether semi-automated data extraction of treatment duration is also feasible and accurate for HAI. Methods: Data from a university-affiliated hospital over the period 1-6-2020 until 1-6-2022 was used for this study. From the Electronic Health Record, raw data on prescriptions, registered indications and admissions was extracted and processed to define treatment courses. In addition, clinical notes including prescription instructions were obtained for the purpose of validation. The derived treatment course was compared to the registered indication and the actual length of treatment (LOT) in the clinical notes in a random sample of 5.7% of treatment courses, to assess the accuracy of the data for both CAI and HAI. Results: Included were 10.564 treatment courses of which 73.1% were CAI and 26.8% HAI. The registered indication matched the diagnosis as recorded in the clinical notes in 79% of treatment courses (79.2% CAI, 78.5% HAI). Higher error rates were seen in urinary tract infections (UTIs) (29.0%) and respiratory tract infections (RTIs) (20.5%) compared to intra-abdominal infections (7.4%), or skin or soft tissue infections (11.1%), mainly due to incorrect specification of the type of UTI or RTI. The LOT was accurately extracted in 98.5% of courses (CAI 98.2%, HAI 99.3%) when compared to prescriptions in the EHR. In 21% of cases however the LOT did not match with the clinical notes, mainly if patients received treatment from other health care providers preceding or following the present course. Conclusion: Semi-automatic data extraction can yield reliable information about the indication and LOT in treatment courses of hospitalized patients, for both HAI and CAI. This can provide stewardship programs with a surveillance tool for all in-hospital treated infections, which can be used to achieve stewardship goals. [ABSTRACT FROM AUTHOR]

Background: Extended illness-death models (a specific class of multistate models) are a useful tool to analyse situations like hospital-acquired infections, ventilation-associated pneumonia, and transfers between hospitals. The main components of these models are hazard rates and transition probabilities. Calculation of different measures and their interpretation can be challenging due to their complexity. Methods: By assuming time-constant hazards, the complexity of these models becomes manageable and closed mathematical forms for transition probabilities can be derived. Using these forms, we created a tool in R to visualize transition probabilities via stacked probability plots. Results: In this article, we present this tool and give some insights into its theoretical background. Using published examples, we give guidelines on how this tool can be used. Our goal is to provide an instrument that helps obtain a deeper understanding of a complex multistate setting. Conclusion: While multistate models (in particular extended illness-death models), can be highly complex, this tool can be used in studies to both understand assumptions, which have been made during planning and as a first step in analysing complex data structures. An online version of this tool can be found at https://eidm.imbi.uni-freiburg.de/. [ABSTRACT FROM AUTHOR]

Nosocomial infections represent a major threat within healthcare systems worldwide, underscoring the critical need for materials with antimicrobial properties. This study presents the development of polyurethane foam embedded with silver nanoparticles (PUF/AgNPs) using a rapid, eco-friendly, in situ radiochemical synthesis method. The nanocomposites were characterized by UV–vis and FTIR spectroscopy, scanning electron microscopy coupled with energy dispersive X-ray technique (SEM/EDX), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), tensile and compression strengths, antimicrobial activity, and foam toxicity tests. The resulting PUF/AgNPs demonstrated prolonged stability (over 12 months) and good dispersion of AgNPs. Also, the samples presented higher levels of hardness compared to samples without AgNPs (deformation of 1682 µm for V1 vs. 4307 µm for V0, under a 5 N force), tensile and compression strength of 1.80 MPa and 0.34 Mpa, respectively. Importantly, they exhibited potent antimicrobial activity against a broad range of bacteria (including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis) and a fungal mixture (no fungal growth on the sample surface was observed after 28 days of exposure). Furthermore, these materials were non-toxic to human keratinocytes, which kept their specific morphology after 24 h of incubation, highlighting their potential for safe use in biomedical applications. We envision promising applications for PUF/AgNPs in hospital bed mattresses and antimicrobial mats, offering a practical strategy to reduce nosocomial infections and enhance patient safety within healthcare facilities. [ABSTRACT FROM AUTHOR]

Successful microbial colonization of the gastrointestinal (GI) tract hinges on an organism's ability to overcome the intense competition for nutrients in the gut between the host and the resident gut microbiome. Enteric pathogens can exploit ethanolamine (EA) in the gut to bypass nutrient competition. However, Klebsiella pneumoniae (K. pneumoniae) is an asymptomatic gut colonizer and, unlike well-studied enteric pathogens, harbors two genetically distinct ethanolamine utilization (eut) loci. Our investigation uncovered unique roles for each eut locus depending on EA utilization as a carbon or nitrogen source. Murine gut colonization studies demonstrated the necessity of both eut loci in the presence of intact gut microbiota for robust GI colonization by K. pneumoniae. Additionally, while some Escherichia coli gut isolates could metabolize EA, other commensals were incapable, suggesting that EA metabolism likely provides K. pneumoniae a selective advantage in gut colonization. Molecular and bioinformatic analyses unveiled the conservation of two eut loci among K. pneumoniae and a subset of the related taxa in the K. pneumoniae species complex, with the NtrC-RpoN regulatory cascade playing a pivotal role in regulation. These findings identify EA metabolism as a critical driver of K. pneumoniae niche establishment in the gut and propose microbial metabolism as a potential therapeutic avenue to combat K. pneumoniae infections. Author summary: Klebsiella pneumoniae (K. pneumoniae) is a leading cause of nosocomial infections but is considered a silent gut colonizer. A molecular understanding of how K. pneumoniae colonizes the GI tract and overcomes host- and resident gut microbiota-mediated colonization resistance requires further investigation. A direct mechanism of colonization resistance is through competition for the same nutrient resources. K. pneumoniae can sidestep nutrient competition by metabolizing ethanolamine as an alternative nutrient source, thus overcoming microbiota-mediated colonization resistance. The unique ethanolamine utilization loci of K. pneumoniae are both required for robust gut colonization and are conserved among K. pneumoniae, suggesting that ethanolamine metabolism is an important mediator of gut colonization. [ABSTRACT FROM AUTHOR]

Background: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. Methods: We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. Results: We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. Conclusions: Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one. [ABSTRACT FROM AUTHOR]

A convenient synthetic strategy has been developed for the synthesis of a pentasaccharide related to the cell wall O‐polysaccharide of Acinetobacter baumannii (A. baumannii) 90 in very good yield applying a stereoselective [3+2] block glycosylation reaction. The synthesis of the target pentasaccharide was challenging due to the presence of a rare sugar, 4‐amino‐4‐deoxy‐D‐fucose and several α‐glycosidic linkages in it. The construction of 1,2‐cis glycosyl linkages were achieved using a combination of copper(II) bromide and tetra‐n‐butylammonium bromide (TBAB) or a combination of N‐iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) as thiophilic glycosylation activator. Perchloric acid supported over silica (HClO4‐SiO2) mediated orthogonal glycosylation reaction has been carried out using glycosyl trichloroacetimidate derivative as donor and thioglycoside as acceptor. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa is a common cause of nosocomial infections. However, the emergence of multidrug-resistant strains has complicated the treatment of P. aeruginosa infections. While polymyxins have been the mainstay for treatment, there is a global increase in resistance to these antibiotics. Therefore, our study aimed to determine the prevalence and molecular details of colistin resistance in P. aeruginosa clinical isolates collected between June 2019 and May 2023, as well as the genetic linkage of colistin-resistant P. aeruginosa isolates. Results: The resistance rate to colistin was 9% (n = 18) among P. aeruginosa isolates. All 18 colistin-resistant isolates were biofilm producers and carried genes associated with biofilm formation. Furthermore, the presence of genes encoding efflux pumps, TCSs, and outer membrane porin was observed in all colistin-resistant P. aeruginosa strains, while the mcr-1 gene was not detected. Amino acid substitutions were identified only in the PmrB protein of multidrug- and colistin-resistant strains. The expression levels of mexA, mexC, mexE, mexY, phoP, and pmrA genes in the 18 colistin-resistant P. aeruginosa strains were as follows: 88.8%, 94.4%, 11.1%, 83.3%, 83.3%, and 38.8%, respectively. Additionally, down-regulation of the oprD gene was observed in 44.4% of colistin-resistant P. aeruginosa strains. Conclusion: This study reports the emergence of colistin resistance with various mechanisms among P. aeruginosa strains in Ardabil hospitals. We recommend avoiding unnecessary use of colistin to prevent potential future increases in colistin resistance. [ABSTRACT FROM AUTHOR]

Dental impressions help the stomatologist to obtain a duplicate of the patient's mouth to have a precise idea of its condition, allowing detailed analysis or work on said impression; but the mouth houses an endless number of microorganisms, these adhere to the impression material, so the stomatologist must disinfect these impressions and thus avoid cross infections. Different studies show that microorganisms can adhere to countless objects; in the literature found does not specifically mention what type of microorganisms can adhere to such materials, so the impressions must be disinfected with special liquids. Unfortunately, in universities the high costs of this disinfectants make them unusable in clinics, and in the Facultad de Estomatología de la Benemérita Universidad Autónoma de Puebla (FEBUAP) is no exception, since in the clinic area this disinfectant it is widely used as a material with high disinfection characteristics. Therefore, there are no previous studies at this university that demonstrate that microorganisms adhere to impressions and whether benzalkonium chloride (BC) really works as a disinfectant. The main purpose of this research is to study the presence of microorganisms after the use of BC in dental impressions, and is undertaken with the purpose of establishing an instructive response to the students of the FEBUAP. [ABSTRACT FROM AUTHOR]

Background: Packed red blood cell (PRBC) transfusion has been shown to increase nosocomial infection risk in the injured population; however, the post-traumatic infectious risk profiles of non-PRBC blood products are less clear. We hypothesized that plasma (fresh frozen plasma [FFP]), platelet (PLT), and cryoprecipitate administration would not be associated with increased rates of nosocomial infections. Patients and Methods: We performed a retrospective, matched, case-control study utilizing the American College of Surgeons National Trauma Data Bank data for 2019. We included all patients who received any volume of PRBC within four hours of presentation. Our outcome of interest was any infection. Controls were matched to cases using individual matching with a desired 1:3 case:control ratio. Bivariable analysis according to infection status, and multivariable logistic regression modeling the development of infection were then performed upon the matched data. Results: A total of 1,563 infectious cases were matched to 3,920 non-infectious controls. First four-hour transfusion volumes for FFP, PLT, and cryoprecipitate in the infection group exceeded those in the control group. The first four-hour FFP transfusion volume (per unit odds ratio [OR], 1.02; 95% confidence interval [CI], 0.99–1.04; p = 0.28) and cryoprecipitate transfusion volume (per unit OR, 1.01; 95% CI, 0.99–1.02; p = 0.43) were similar in cases and controls whereas PLT transfusion volume (per unit OR, 0.92; 95% CI, 0.86–0.98; p = 0.01) was lower in cases of infection than in controls. Conclusions: Fresh frozen plasma, PLT, and cryoprecipitate transfusion volumes were not independent risk factors for the development of nosocomial infection in a trauma population. PLT transfusion volume was associated with less infection. [ABSTRACT FROM AUTHOR]

The genus Acinetobacter comprises both environmental and clinically relevant species associated with hospital-acquired infections. Among them, Acinetobacter baumannii is a critical priority bacterial pathogen, for which the research and development of new strategies for antimicrobial treatment are urgently needed. Acinetobacter spp. produce a variety of structurally diverse capsular polysaccharides (CPSs), which surround the bacterial cells with a thick protective layer. These surface structures are primary receptors for capsule-specific bacteriophages, that is, phages carrying tailspikes with CPS-depolymerizing/modifying activities. Phage tailspike proteins (TSPs) exhibit hydrolase, lyase, or esterase activities toward the corresponding CPSs of a certain structure. In this study, the data on all lytic capsule-specific phages infecting Acinetobacter spp. with genomes deposited in the NCBI GenBank database by January 2024 were summarized. Among the 149 identified TSPs encoded in the genomes of 143 phages, the capsular specificity (K specificity) of 46 proteins has been experimentally determined or predicted previously. The specificity of 63 TSPs toward CPSs, produced by various Acinetobacter K types, was predicted in this study using a bioinformatic analysis. A comprehensive phylogenetic analysis confirmed the prediction and revealed the possibility of the genetic exchange of gene regions corresponding to the CPS-recognizing/degrading parts of different TSPs between morphologically and taxonomically distant groups of capsule-specific Acinetobacter phages. [ABSTRACT FROM AUTHOR]

Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high risk of developing hospital-acquired infections, with longer patient stays leading to increased chances of acquiring such drug-resistant infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis are the most common multidrug-resistant (MDR) Gram-negative bacteria identified in burn wound infections (BWIs). BWIs caused by viruses, like herpes simplex and varicella zoster, and fungi-like Candida species appear to occur occasionally. However, the preponderance of infection by opportunistic pathogens is very high in burn patients. Variations in the causative agents of BWIs are due to differences in geographic location and infection control measures. Overall, burn injuries are characterized by elevated serum cytokine levels, systemic immune response, and immunosuppression. Hence, early detection and treatment can accelerate the wound-healing process and reduce the risk of further infections at the site of injury. A multidisciplinary collaboration between burn surgeons and infectious disease specialists is also needed to properly monitor antibiotic resistance in BWI pathogens, help check the super-spread of MDR pathogens, and improve treatment outcomes as a result. Key Words: burn wound infections; biofilm; epidermis; hospital; opportunistic infection [ABSTRACT FROM AUTHOR]

The purpose of this review is both to evaluate the impact of the association of nosocomial infections, dental and somatic pathology in patients with depression, because the presence of comorbidities leads to an increase in health care costs, as well as to evaluate the importance of multidisciplinary care of these patients. Chronic depression correlated, independently, more frequently with the state of somatic health compared to episodic depression thus emphasizing the need for prompt treatment of depression. Nosocomial infections associated with depression are a constant concern in the medical field, despite significant advances in patient care. These infections, occurring within medical institutions, constitute a major problem in the health system, generating significant morbidity and mortality, and involving substantial socio-economic costs. There is a higher prevalence of cardiovascular diseases and strokes in patients suffering from recurrent depressive disorder. It is possible that anxiety through serotonergic dysfunction represents the physio-pathological link that establishes the depressionanxiety-somatic pathology connection. The physical health of patients with depression must also include prevention of oral pathology through oral hygiene advice, management of iatrogenic dry mouth and early dental visits. Osteo-articular diseases increase the risk of suicide, while cardiovascular diseases lead to an increase in the frequency of episodes and hospitalizations. [ABSTRACT FROM AUTHOR]

Background: Hospital-acquired influenza (HAI) is under-recognized despite its high morbidity and poor health outcomes. The early detection of HAI is crucial for curbing its transmission in hospital settings. Aim: This study aimed to investigate factors related to HAI, develop predictive models, and subsequently compare them to identify the best performing machine learning algorithm for predicting the occurrence of HAI. Methods: This retrospective observational study was conducted in 2022 and included 111 HAI and 73,748 non-HAI patients from the 2011–2012 and 2019–2020 influenza seasons. General characteristics, comorbidities, vital signs, laboratory and chest X-ray results, and room information within the electronic medical record were analysed. Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGB), and Artificial Neural Network (ANN) techniques were used to construct the predictive models. Employing randomized allocation, 80% of the dataset constituted the training set, and the remaining 20% comprised the test set. The performance of the developed models was assessed using metrics such as the area under the receiver operating characteristic curve (AUC), the count of false negatives (FN), and the determination of feature importance. Results: Patients with HAI demonstrated notable differences in general characteristics, comorbidities, vital signs, laboratory findings, chest X-ray result, and room status compared to non-HAI patients. Among the developed models, the RF model demonstrated the best performance taking into account both the AUC (83.3%) and the occurrence of FN (four). The most influential factors for prediction were staying in double rooms, followed by vital signs and laboratory results. Conclusion: This study revealed the characteristics of patients with HAI and emphasized the role of ventilation in reducing influenza incidence. These findings can aid hospitals in devising infection prevention strategies, and the application of machine learning-based predictive models especially RF can enable early intervention to mitigate the spread of influenza in healthcare settings. [ABSTRACT FROM AUTHOR]

Background: Ventilator-associated pneumonia (VAP) is defined as infection of lung parenchyma in patients exposed to invasive mechanical ventilation for at least 48 h. VAP is the second most common hospital-acquired infection with a mortality rate up to 40%. Aims and Objectives: To determine the microbiological profile of VAP-related samples, the demographic profile of patients, and associated risk factors. Materials and Methods: VAPrelated samples including endotracheal tube tip, tracheal secretions, and bronchoalveolar lavage (BAL) fluid were collected from 73 patients during the study period from January 2023 to November 2023. Their blood samples were also collected for automated blood culture. Samples were processed as per standard protocol. Results: Out of the total patients, 60.31% were male and 39.68% were female. 61-80 years was the most commonly affected age group. The most commonly isolated micro-organism was Acinetobacter baumannii with the highest sensitivity to polymixin B and tigecycline. Associated blood culture positivity was maximum in patients whose samples of ET tube tip, tracheal secretions, and BAL fluid had isolated A. baumannii and Klebsiella pneumoniae. Two Candida albicans were isolated with sensitivities to voriconazole and amphotericin B. Many patients had associated septicemia. Endotracheal intubation and tracheal suction were the most common risk factors associated. Conclusion: As associated septicemia may increase the mortality rate manifold blood samples should also be collected in suspected VAP patients along with VAP-related samples for early detection of sepsis leading to better patient management. [ABSTRACT FROM AUTHOR]

Background: A national point prevalence survey (PPS) of healthcare-associated infections (HAI) and antibiotic use (AU) was carried out in Germany in 2022 in the framework of the European PPS conducted by the European Centre for Disease Prevention and Control (ECDC). The objective was to determine the prevalence of HAI and AU in German hospitals and to compare the obtained values with those of the most recent previous PPS, which was carried out in 2016. Methods: The German National Reference Center for the Surveillance of Nosocomial Infections was entrusted with the organization of the PPS of 2022. As recommended by the ECDC, each hospital in a representative sample of 50 hospitals was invited to participate, and all other interested hospitals in Germany were also able to participate if desired. The data were collected by specially trained hospital staff in May, June, and July 2022. The definitions and methods put forth by the ECDC were used. Results: Data from 66 586 patients in 252 hospitals were included. The prevalence of HAI in all participating hospitals was 4.9%, and that of AU was 26.9%. The HAI and AU prevalences were essentially unchanged in comparison to 2016. The most common types of HAI were surgical site infection (23.5%), lower respiratory tract infection (21.6%), and urinary tract infection (19.0%). Conclusion: HAI were just as frequent in 2022 as in 2016, affecting approximately one in twenty hospitalized patients on any given day. Cite this as: Aghdassi SJS, Hansen S, Peña Diaz LA, Gropmann A, Saydan S, Geffers C, Gastmeier P, Piening B, Behnke M: Healthcare-associated infections and the use of antibiotics in German hospitals--results of the point prevalence survey of 2022 and comparison with earlier findings. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa is an opportunistic pathogen that represents a global public health threat. Immunocompromised hosts and cystic fibrosis patients are primarily susceptible to high morbidity and mortality due to pulmonary tract colonization with mucoid Pseudomonas aeruginosa. Differentially expressed virulence factors govern Pseudomonas aeruginosa pathogenicity in different sites of infection. Therefore, the detection of site-specific virulence genes in Pseudomonas aeruginosa isolates may potentially predict the level of Pseudomonas aeruginosa pathogenicity and the outcome in infected patients. Objectives: This study aims to phenotypically and genotypically characterize nosocomial Pseudomonas aeruginosa isolates from different clinical specimens to determine the frequency of LasB, ExoS and Nan1 virulence genes in the collected isolates relative to the site and severity of Pseudomonas aeruginosa infection using conventional polymerase chain reaction. Methods: The study was carried out on 30 Pseudomonas aeruginosa isolates collected from hospitalized patients who have been diagnosed with respiratory tract, bloodstream or burn infection in Tanta University Hospitals. Pseudomonas aeruginosa isolates were phenotypically characterized using standard microbiology techniques and genotypically characterized using conventional PCR for the detection of LasB, ExoS and Nan1 virulence genes. Results: Both Nan1 and ExoS genes were detected in Pseudomonas aeruginosa isolates from 30% of respiratory and burn infections but they were undetectable in all isolates from bloodstream infections. While, LasB gene was detected in all types of clinical specimens (100% of respiratory specimens, 90% of pus and 90% of blood specimens). A significant correlation was found between the site, severity of infection and the presence of multiple virulence genes. Conclusion: Our study reveals site and severity specific detection of certain Pseudomonas aeruginosa virulence genes which may suggest site and severity specific pathogenesis of certain Pseudomonas aeruginosa strains. Our data also imply that precision targeting of specific virulence factors detected in certain infection sites and/or severity should improve therapeutic outcomes of Pseudomonas aeruginosa infections. [ABSTRACT FROM AUTHOR]

Background: Pseudomonas (P. aeruginosa) is a worrisome multidrug (MDR) or even extensively drug-resistant (XDR) nosocomial pathogen. Ceftolozane/tazobactam(C/T) and ceftazidime/avibactam (CAZ/AVI), novel combinations, were recently approved for the treatment of MDR Gram-negative pathogens. Objective: To assess the in vitro activity of C/T & CAZ/AVI and against MDR/XDR P. aeruginosa isolates, detect the synergistic activity of CAZ/AVI plus aztreonam (ATM) against metallo-ß-lactamase) MßL(producers and to determine the virulence profile of the studied isolates. Methods: Eighty P. aeruginosa strains were isolated from hospitalized patients and screened for their antimicrobial susceptibility pattern by disk diffusion test. Different resistance mechanisms; beta-lactam hydrolyzing enzymes (ESßLs, AmpC, and class A & B carbapenemases), biofilm production and efflux pump-mediated colistin resistance mechanisms were characterized by the corresponding phenotypic methods. Multiplex PCR verified some resistance (blaVIM, blaKPC, mcr-1 & mcr-2) and virulence (exoU and exoS) genes. We applied E-test strip superposition method to detect synergistic effect between CAZ/AVI and ATM. Results: 32.5% and 52.5% of P. aeruginosa isolates were recovered as MDR and XDR isolates respectively. The frequency of beta-lactamase production reached 12.5% for ESßLs, 46.25% for AmpC, 21.4% for class A and 55.4% for class B carbapenemases. About 81.3% and 63.7% of the isolates proved susceptibility to CAZ/AVI and C/T respectively. While only 36.3% were ATM susceptible. Interestingly, combined use of CAZ/AVI with ATM completely restored susceptibility among MßL strains. Conclusion: Synergistic combination of CAZ/AVI with ATM could be promising therapy against MDR/XDR P. aeruginosa infections with MßL production. [ABSTRACT FROM AUTHOR]

Background: Enterococci, particularly those that produce biofilm, can cause different infections ranging from simple infections to sepsis. This study aims to understand the effect of sub-inhibitory concentrations of antibiotics (ampicillin, vancomycin, ciprofloxacin and tetracycline) on biofilm formation of Enterococcus and its association with virulence genes (asa1, esp and gel E). Methods: This cross-sectional study included Enterococci strains isolated from different microbiological samples. Disk diffusion and microtiter plate techniques were used to examine the isolates antibiotic sensitivity and biofilm production respectively. Isolates were investigated for asa1, esp and gel E genes using multiplex PCR. Minimum inhibitory concentration (MIC) of ampicillin, vancomycin, ciprofloxacin, and tetracycline for strong biofilm forming isolates was determined by broth microdilution then the sub-MIC effect of these antibiotics on their biofilm formation was evaluated. Results: A total of 80 Enterococcus (65 Enterococcus faecalis and 15 Enterococcus faecium) strains were identified. Compared to Enterococcus faecalis, Enterococcus faecium showed higher antibiotics resistance and lower biofilm formation. asa 1, esp and gel E genes were detected in 44.6%, 60.0% and 76.9% of Enterococcus faecalis and 40.0%, 33.3% and 26.7% of Enterococcus faecium respectively with higher frequency of these genes among biofilm forming isolates. Of the four selected antibiotics, sub-inhibitory concentrations of only ampicillin and vancomycin significantly enhanced biofilm density of Enterococcus faecalis while Enterococcus faecium was not significantly affected. Conclusion: Increased biofilm formation in some isolates at different sub-MIC ensures the significance of appropriate antibiotic use to reduce the danger of resistant bacteria selection. [ABSTRACT FROM AUTHOR]

Spontaneous Bacterial Peritonitis (SBP) is a serious complication and a common cause of death in patients with liver cirrhosis. Between January 2017 and March 2024, a retrospective study was conducted involving 302 patients (>18 years old) with ascites treated at a tertiary referral center in south-eastern Poland. Microbiological analysis of the ascitic fluids was performed in all patients. The presence of microorganisms was found in samples from 17 patients, and 21 pathogens were isolated, including 15 Gram-positive bacteria and 6 Gram-negative bacteria. Staphylococcus epidermidis, MRCNS (methicillin-resistant coagulase-negative staphylococci, resistant to all beta-lactam antibiotics: penicillins, penicillins with beta-lactamase inhibitor, cephalosporins and carbapenems) was the main pathogen detected (19.05%, 4/21), followed by Enterococcus faecalis (9.52%, 2/21), Enterococcus faecium (9.52%, 2/21), Staphylococcus haemolyticus, MRCNS (4.76%, 1/21), Streptococcus mitis (9.52%, 2/21), Streptococcus parasanguinis (9.52%, 2/21), Micrococcus luteus (4.76%, 1/21) and Bacillus spp. (4.76%, 1/21). The following Gram-negative bacteria were also found in the specimens examined: Escherichia coli, ESBL (extended-spectrum β-lactamase producing E. coli) (4.76%, 1/21), Escherichia coli (4.76%, 1/21), Pseudomonas aeruginosa (4.76%, 1/21), Klebsiella oxytoca (9.52%, 2/21) and Sphingomonas paucimobilis (4.76%, 1/21). Gram-positive bacteria caused nosocomial infections in nine patients with SBP, Gram-negative bacteria caused nosocomial infections in two patients. In six patients with SBP, community-acquired infections caused by Gram-negative bacteria were found in three cases, Gram-positive bacteria in two cases, and in one case, community-acquired infection was caused by mixed Gram-positive and Gram-negative. Bacteria isolated from patients with hospital-acquired SBP showed higher drug resistance than those found in patients with non-hospital SBP. Bacterial infections in cirrhotic patients with complications may be responsible for their deteriorating health. Prompt intervention is critical to reducing mortality. [ABSTRACT FROM AUTHOR]

Legionella pneumophila can cause a large panel of symptoms besides the classic pneumonia presentation. Here we present a case of fatal nosocomial cellulitis in an immunocompromised patient followed, a year later, by a second case of Legionnaires' disease in the same ward. While the first case was easily assumed as nosocomial based on the date of symptom onset, the second case required clear typing results to be assigned either as nosocomial and related to the same environmental source as the first case, or community acquired. To untangle this specific question, we applied core-genome multilocus typing (MLST), whole-genome single nucleotide polymorphism and whole-genome MLST methods to a collection of 36 Belgian and 41 international sequence-type 1 (ST1) isolates using both thresholds recommended in the literature and tailored threshold based on local epidemiological data. Based on the thresholds applied to cluster isolates together, the three methods gave different results and no firm conclusion about the nosocomial setting of the second case could been drawn. Our data highlight that despite promising results in the study of outbreaks and for large-scale epidemiological investigations, next-generation sequencing typing methods applied to ST1 outbreak investigation still need standardization regarding both wet-lab protocols and bioinformatics. A deeper evaluation of the L. pneumophila evolutionary clock is also required to increase our understanding of genomic differences between isolates sampled during a clinical infection and in the environment. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae (K. pneumoniae) cultures from a hospital-wide outbreak in the UK, which lasted for over 12 months, were sequenced. We sought to sequence and genetically characterise the outbreak strain. Antibiotic Susceptibility Testing (AST) was performed on 65 K. pneumoniae isolates saved from the outbreak. All isolates were sequenced using the Oxford Nanopore Technologies (ONT) MinION flowcell: 10 isolates, including the isolate with the earliest collection date in 2017, were additionally sequenced on the NovaSeq 6000 platform to build high-accuracy nanopore-illumina assemblies. Among the sequenced strains, 60 were typed as ST628. 96.6% (n = 58/60) ST628 strains harboured a large ~247-kb FIB(K) plasmid carrying up to 11 antimicrobial resistance genes, including the extended-spectrum beta-lactamase (ESBL) gene, blaCTX-M-15. Clonality between the outbreak isolates was confirmed using single nucleotide polymorphism (SNP) typing. The outbreak strains were phylogenetically related to clinical ST628 strains identified in 2012, 6 years prior to the outbreak. A rare ESBL K. pneumoniae K2 ST628 strain harbouring a multi-drug resistant (MDR) plasmid encoding the ESBL gene blaCTX-M-15 was detected across multiple independent wards during the protracted nosocomial outbreak. Surveillance of this strain is recommended to prevent future nosocomial outbreaks. [ABSTRACT FROM AUTHOR]

Pneumonia is a global health concern, causing significant morbidity and mortality, particularly among vulnerable populations. This study, conducted at Dr. Soetomo Regional Public Hospital (RSUD Dr. Soetomo), Surabaya, Indonesia, aimed to assess the causative pathogens, antibiotic sensitivity patterns, and the impact of empiric therapy on the clinical outcomes of pneumonia patients. The present study analyzed 324 cases from January to March 2023, categorizing pneumonia as communityacquired (CAP), hospital-acquired (HAP), and ventilator-associated (VAP). Gram-negative bacteria, predominantly Klebsiella pneumoniae, were the primary pathogens, with 44% being multidrug-resistant. Antibiotic sensitivity patterns highlighted the efficacy of amikacin, cefoperazone sulbactam, and meropenem against Gram-negative bacteria. Empiric therapy, mainly monotherapy, showed varied outcomes across pneumonia types. Clinical improvement was observed in 72.5% of CAP patients, while HAP and VAP patients faced challenges, with high mortality rates of 47.2% and 89.1%, respectively. Clinical stability in CAP correlated with age, culture results, multidrug resistance, pneumonia severity, and antibiotic class. In HAP, appropriate empiric therapy and pneumonia severity influenced clinical outcomes. Notably, VAP patients experienced poor outcomes irrespective of the variables studied. This study underscores the importance of local pathogen prevalence awareness and tailored empiric therapy to enhance pneumonia management, especially in HAP and VAP cases. Further research is warranted to refine treatment strategies and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Hospital-acquired infections (HAIs) pose a significant risk to global health, impacting millions of individuals globally. These infections have increased rates of morbidity and mortality due to the prevalence of widespread antimicrobial resistance (AMR). Graphene-based nanoparticles (GBNs) are known to possess extensive antimicrobial properties by inflicting damage to the cell membrane, suppressing virulence, and inhibiting microbial biofilms. Developing alternative therapies for HAIs and addressing AMR can be made easier and more affordable by combining nanoparticles with medicinal plants harboring antimicrobial properties. Hence, this study was undertaken to develop a novel graphene–silver nanocomposite via green synthesis using Trillium govanianum plant extract as a reducing agent. The resulting nanocomposite comprised silver nanoparticles embedded in graphene sheets. The antibacterial and antifungal properties of graphene–silver nanocomposites were investigated against several nosocomial pathogens, namely, Candida auris, Candida glabrata, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The nanocomposite displayed broad-range antimicrobial potential against the test pathogens, with minimum inhibitory concentrations (MICs) ranging between 31.25 and 125.0 µg/mL, and biofilm inhibition up to 80–96%. Moreover, nanocomposite-functionalized urinary catheters demonstrated hemocompatibility towards sheep erythrocytes and imparted anti-fouling activity to the biomaterial, while also displaying biocompatibility towards HEK 293 cells. Collectively, this investigation highlights the possible application of green-synthesized GBNs as an effective alternative to conventional antibiotics for combating multidrug-resistant pathogens. [ABSTRACT FROM AUTHOR]

In an era of increasing antibiotic resistance among pathogens, the treatment options for infectious diseases are diminishing. One of the clinical groups especially vulnerable to this threat are patients who are hospitalized in intensive care units due to ventilator-associated pneumonia caused by multidrug-resistant/extensively drug-resistant Gram-negative bacteria. In order to prevent the exhaustion of therapeutic options for this life-threatening condition, there is an urgent need for new pharmaceuticals. Novel β-lactam antibiotics, including combinations of cephalosporins with β-lactamase inhibitors, are proposed as a solution to this escalating problem. The unique mechanism of action, distinctive to this new group of siderophore cephalosporins, can overcome multidrug resistance, which is raising high expectations. In this review, we present the summarized results of clinical trials, in vitro studies, and case studies on the therapeutic efficacy of cefoperazone-sulbactam, ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol in the treatment of ventilator-associated pneumonia. We demonstrate that treatment strategies based on siderophore cephalosporins and combinations of β-lactams with β-lactamases inhibitors show comparable or higher clinical efficacy than those used with classic pharmaceuticals, like carbapenems, colistin, or tigecycline, and are often associated with a lower risk of adverse events. [ABSTRACT FROM AUTHOR]

Patients hospitalized in ICUs with severe COVID-19 are at risk for developing hospital-acquired infections, especially infections caused by Pseudomonas aeruginosa. We aimed to describe the evolution of P. aeruginosa infections in ICUs at CHRU-Nancy (France) in patients with severe COVID-19 during the three initial waves of COVID-19. The second aims were to analyze P. aeruginosa resistance and to describe the antibiotic treatments. We conducted a retrospective cohort study among adult patients who were hospitalized for acute respiratory distress syndrome due to COVID-19 and who developed a hospital-acquired infection caused by P. aeruginosa during their ICU stay. Among the 51 patients included, most were male (90%) with comorbidities (77%), and the first identification of P. aeruginosa infection occurred after a median ICU stay of 11 days. Several patients acquired infections with MDR (27%) and XDR (8%) P. aeruginosa strains. The agents that strains most commonly exhibited resistance to were penicillin + β-lactamase inhibitors (59%), cephalosporins (42%), monobactams (32%), and carbapenems (27%). Probabilistic antibiotic treatment was prescribed for 49 patients (96%) and was subsequently adapted for 51% of patients after antibiogram and for 33% of patients after noncompliant antibiotic plasma concentration. Hospital-acquired infection is a common and life-threatening complication in critically ill patients. Efforts to minimize the occurrence and improve the treatment of such infections, including infections caused by resistant strains, must be pursued. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii (AB) is a gram-negative bacterium and a main source of nosocomial infection that mainly affect immunocompromised individuals. Methylene blue (MB) is commonly used for staining in microbiology but in this article MB is used as resisting agent against AB. The main aim of this study is to find the most possible cure against A. baunannii. Isolated strains of A. baumannii were subcultured on Muller-Hinton agar (MHA) containing MB and sub-cultured on eosin methylene blue (EMB). Then antibiotic susceptibility testing (AST) and minimum inhibitory concentration (MIC) were determined. The A. baumannii isolates were highly inhibited by EMB medium but showed growth on MHA plates containing MB. The results infer that A. baumannii shows sensitivity against Meropenem. In-vitro studied effect of methylene blue shows inhibition against carbapenem resistance A. baumannii growth was also inhibited by EMB agar. AB strains showed sensitivity against synergistic combinational drugs (Meropenem + Amikacin), (Meropenem + Ciprofloxacin) (Imipenem + Tobramycin), these strains showed resistance against additive combinational drugs (Meropenem + Cefepime) and (Imipenem + Tobramycin), (Ciprofloxacin), (Cefepime) as compared with individually. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effectiveness of linezolid and vancomycin for the treatment of nosocomial infections in children under 12 years old. Data sources: This is a systematic review in which five randomized clinical trials about the effectiveness of linezolid and vancomycin, involving a total of 429 children with nosocomial infections, were evaluated. They were searched in scientific databases: PubMed, Bvs, and SciELO. Summary of findings: The main nosocomial infections that affected children were bacteremia, skin, and soft tissue infections followed by nosocomial pneumonia. Most infections were caused by Gram-positive bacteria, which all studies showed infections caused by Staphylococcus aureus, with methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci strains being isolated. Both linezolid and vancomycin showed high therapeutic efficacy against different types of nosocomial infections, ranging from 84.4% to 94% for linezolid and 76.9% to 90% for vancomycin. Patients receiving linezolid had lower rates of rash and red man syndrome compared to those receiving vancomycin. However, despite the adverse reactions, antimicrobials can be safely administered to children to treat nosocomial infections caused by resistant Gram-positive bacteria. Conclusion: Both linezolid and vancomycin showed good efficacy in the treatment of bacterial infections caused by resistant Gram-positive bacteria in hospitalized children. However, linezolid stands out regarding its pharmacological safety. Importantly, to strengthen this conclusion, further clinical trials are needed to provide additional evidence. [ABSTRACT FROM AUTHOR]

In recent years, antibiotic therapy has encountered significant challenges due to the rapid emergence of multidrug resistance among bacteria responsible for life‐threatening illnesses, creating uncertainty about the future management of infectious diseases. The escalation of antimicrobial resistance in the post‐COVID era compared to the pre‐COVID era has raised global concern. The prevalence of nosocomial‐related infections, especially outbreaks of drug‐resistant strains of Staphylococcus aureus, have been reported worldwide, with India being a notable hotspot for such occurrences. Various virulence factors and mutations characterize nosocomial infections involving S. aureus. The lack of proper alternative treatments leading to increased drug resistance emphasizes the need to investigate and examine recent research to combat future pandemics. In the current genomics era, the application of advanced technologies such as next‐generation sequencing (NGS), machine learning (ML), and quantum computing (QC) for genomic analysis and resistance prediction has significantly increased the pace of diagnosing drug‐resistant pathogens and insights into genetic intricacies. Despite prompt diagnosis, the elimination of drug‐resistant infections remains unattainable in the absence of effective alternative therapies. Researchers are exploring various alternative therapeutic approaches, including phage therapy, antimicrobial peptides, photodynamic therapy, vaccines, host‐directed therapies, and more. The proposed review mainly focuses on the resistance journey of S. aureus over the past decade, detailing its resistance mechanisms, prevalence in the subcontinent, innovations in rapid diagnosis of the drug‐resistant strains, including the applicants of NGS and ML application along with QC, it helps to design alternative novel therapeutics approaches against S. aureus infection. [ABSTRACT FROM AUTHOR]

Medical devices such as venous catheters (VCs) and urinary catheters (UCs) are widely used in the hospital setting. However, the implantation of these devices is often accompanied by complications. About 60 to 70% of nosocomial infections (NIs) are linked to biofilms. The main complication is the ability of microorganisms to adhere to surfaces and form biofilms which protect them and help them to persist in the host. Indeed, by crossing the skin barrier, the insertion of VC inevitably allows skin flora or accidental environmental contaminants to access the underlying tissues and cause fatal complications like bloodstream infections (BSIs). In fact, 80,000 central venous catheters—BSIs (CVC-BSIs)—mainly occur in intensive care units (ICUs) with a death rate of 12 to 25%. Similarly, catheter-associated urinary tract infections (CA-UTIs) are the most commonlyhospital-acquired infections (HAIs) worldwide.These infections represent up to 40% of NIs.In this review, we present a summary of biofilm formation steps. We provide an overview of two main and important infections in clinical settings linked to medical devices, namely the catheter-asociated bloodstream infections (CA-BSIs) and catheter-associated urinary tract infections (CA-UTIs), and highlight also the most multidrug resistant bacteria implicated in these infections. Furthermore, we draw attention toseveral useful prevention strategies, and advanced antimicrobial and antifouling approaches developed to reduce bacterial colonization on catheter surfaces and the incidence of the catheter-related infections. [ABSTRACT FROM AUTHOR]

To compare the epidemiological characteristics and drug resistance of Burkholderia cepacia isolated from blood cultures, and to provide data support and a scientific basis for the clinical treatment and detection of hospital infections. Methods: The Hebei Province Antimicrobial Surveillance Network received 349 B. cepacia strains isolated from blood cultures reported by 83 hospitals, from 2016 to 2021. These strains were identified by MALDI-TOF MS and, the antibiotic sensitivity tests were carried out using the VITEK 2 COMPACT system. The 2023 Institute of Clinical and Laboratory Standardization drug-susceptibility breakpoints were used for drug susceptibility testing and the data were analyzed using WHONET5.6 software. Results: A total of 349 B. cepacia strains were isolated from 2016 to 2021, including 68 strains from secondary hospitals and 281 strains from tertiary hospitals. The ratios of male: female patients with B. cepacia bloodstream infections in all hospitals, secondary hospitals, and tertiary hospitals were 1.49:1 (209/140), 2.09:1 (46/22), and 1.38:1 (163/118), respectively. Most B. cepacia strains were isolated in intensive care units (ICUs), followed by internal medicine departments, accounting for 49.57% (173/349) and 22.92% (80/349), respectively. Regarding the age distribution, most patients were elderly (> 65 years, 57.59%, 201/349), with numbers of patients gradually declining with decreasing of age. The resistance rates for levofloxacin, ceftazidime, and sulfamethoxazole decreased over the 6-year period (P< 0.05), while there were no significant changes in the resistance rates for meropenem, chloramphenicol, and minocycline (P> 0.05). There was no significant difference in drug-resistance rates between secondary and tertiary hospitals (P> 0.05). Conclusion: Attention should be paid to bloodstream infections caused by B. cepacia, especially elderly patients and patients admitted to the ICU. The difficult treatment characteristics of B. cepacia bloodstream infections mean that laboratories and clinicians should pay careful attention to drug resistance to provide a basis for their prevention and empirical treatment. [ABSTRACT FROM AUTHOR]

Background: Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP. Methods: We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events. Results: Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17–0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19–3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00–2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03–2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02–2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin. Conclusions: This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria. Registration PROSPERO CRD42021226603 [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae, a notorious pathogen for causing nosocomial infections has become a major cause of neonatal septicemia, leading to high morbidity and mortality worldwide. This opportunistic bacterium has become highly resistant to antibiotics due to the widespread acquisition of genes encoding a variety of enzymes such as extended-spectrum beta-lactamases (ESBLs) and carbapenemases. We collected Klebsiella pneumoniae isolates from a local tertiary care hospital from February 2019–February 2021. To gain molecular insight into the resistome, virulome, and genetic environment of significant genes of multidrug-resistant K. pneumoniae isolates, we performed the short-read whole-genome sequencing of 10 K. pneumoniae isolates recovered from adult patients, neonates, and hospital tap water samples. Results: The draft genomes of the isolates varied in size, ranging from 5.48 to 5.96 Mbp suggesting the genome plasticity of this pathogen. Various genes conferring resistance to different classes of antibiotics e.g., aminoglycosides, quinolones, sulfonamides, tetracycline, and trimethoprim were identified in all sequenced isolates. The highest resistance was observed towards carbapenems, which has been putatively linked to the presence of both class B and class D carbapenemases, blaNDM, and blaOXA, respectively. Moreover, the biocide resistance gene qacEdelta1 was found in 6/10 of the sequenced strains. The sequenced isolates exhibited a broad range of sequence types and capsular types. The significant antibiotic resistance genes (ARGs) were bracketed by a variety of mobile genetic elements (MGEs). Various spontaneous mutations in genes other than the acquired antibiotic-resistance genes were observed, which play an indirect role in making these bugs resistant to antibiotics. Loss or deficiency of outer membrane porins, combined with ESBL production, played a significant role in carbapenem resistance in our sequenced isolates. Phylogenetic analysis revealed that the study isolates exhibited evolutionary relationships with strains from China, India, and the USA suggesting a shared evolutionary history and potential dissemination of similar genes amongst the isolates of different origins. Conclusions: This study provides valuable insight into the presence of multiple mechanisms of carbapenem resistance in K. pneumoniae strains including the acquisition of multiple antibiotic-resistance genes through mobile genetic elements. Identification of rich mobilome yielded insightful information regarding the crucial role of insertion sequences, transposons, and integrons in shaping the genome of bacteria for the transmission of various resistance-associated genes. Multi-drug resistant isolates that had the fewest resistance genes exhibited a significant number of mutations. K. pneumoniae isolate from water source displayed comparable antibiotic resistance determinants to clinical isolates and the highest number of virulence-associated genes suggesting the possible interplay of ARGs amongst bacteria from different sources. [ABSTRACT FROM AUTHOR]

Nosocomial infections are a significant threat to public health that leads to substantial morbidity and mortality. The emergence and spread of antibiotic-resistant organisms have compounded the complexity of managing these infections, highlighting the urgent need for innovative and effective strategies to combat them. Photostimuli-responsive nanomaterials have emerged as promising tools for coating biomedical devices and tools against nosocomial infections due to their ability to selectively target and kill pathogenic bacteria and fungi. It is feasible to develop antibacterial surfaces by integrating photothermal agents (PTAs), photodynamic agents (PDAs), and both PTAs and PDAs into coatings. When exposed to light, PTAs generate heat that can be used to kill bacteria, while PDAs emit reactive oxygen species (ROS) that can also be used to kill bacteria. The combination of photothermal and photodynamic therapies produces a synergistic effect in which the death of bacteria is boosted in comparison with the use of each individual therapy. These coatings have the potential to provide enhanced bacterial control for a number of biomedical devices, including implants, catheters, meshes, and wound dressings. The utilization of antimicrobial nanomaterials offers a promising approach for reducing the risk of infections associated with the use of these devices. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a major inducement of nosocomial infections and its biofilm formation render the high tolerance to conventional antibiotics, which highlights the requirement to develop new antimicrobial agents urgently. In this study, we identified a fluorinated benzimidazole derivative, TFBZ, with potent antibacterial efficacy toward planktonic MRSA (MIC = 4 µg/mL, MBC = 8 µg/mL) and its persistent biofilms (=99%, MBEC = 8 µg/mL). TFBZ manifested significant irreversible timedependent killing against MRSA as characterized by diminished cell viability, bacterial morphological change and protein leakage. Furthermore, the results from CBD devices, crystal violet assay in conjunction with live/dead staining and scanning electron microscopy confirmed that TFBZ was capable of eradicating preformed MRSA biofilms with high efficiency. Simultaneously, TFBZ reduced the bacterial invasiveness and exerted negligible hemolysis and cytotoxicity toward mammalian cells, which ensuring the robust therapeutic effect on mouse skin abscess model. The transcriptome profiling and quantitative RT-PCR revealed that a set of encoding genes associated with cell adhesion, biofilm formation, translation process, cell wall biosynthesis was consistently downregulated in MRSA biofilms upon exposure to TFBZ. In conclusion, TFBZ holds promise as a valuable candidate for therapeutic applications against MRSA chronic infections. [ABSTRACT FROM AUTHOR]

Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many antimicrobial stewardship programs and is believed to reduce patients' exposure to broad-spectrum antibiotics and prevent resistance. However, the ecological benefits of de-escalation have not been universally observed in clinical studies. This paper conducts computer simulations to assess the ecological effects of de-escalation on the resistance prevalence of Pseudomonas aeruginosa—a frequent pathogen causing nosocomial infections. Synthetic data produced by the models are then used to estimate the sample size and study period needed to observe the predicted effects in clinical trials. Our results show that de-escalation can reduce colonization and infections caused by bacterial strains resistant to the empiric antibiotic, limit the use of broad-spectrum antibiotics, and avoid inappropriate empiric therapies. Further, we show that de-escalation could reduce the overall super-infection incidence, and this benefit becomes more evident under good compliance with hand hygiene protocols among health care workers. Finally, we find that any clinical study aiming to observe the essential effects of de-escalation should involve at least ten arms and last for four years—a size never attained in prior studies. This study explains the controversial findings of de-escalation in previous clinical studies and illustrates how mathematical models can inform outcome expectations and guide the design of clinical studies. [ABSTRACT FROM AUTHOR]

Background: Device-related bacterial infections account for a large proportion of hospital-acquired infections. The ability of bacteria to form a biofilm as a protective shield usually makes treatment impossible without removal of the implant. Topographic surfaces have attracted considerable attention in studies seeking antibacterial properties without the need for additional antimicrobial substances. As there are still no valid rules for the design of antibacterial microstructured surfaces, a fast, reproducible production technique with good resolution is required to produce test surfaces and to examine their effectiveness with regard to their antibacterial properties. Methods: In this work various surfaces, flat and with microcylinders in different dimensions (flat, 1, 3 and 9 μm) with a surface area of 7 × 7 mm were fabricated with a nanoprinter using two-photon lithography and evaluated for their antibiofilm effect. The microstructured surfaces were cultured for 24 h with different strains of Pseudomonas aeruginosa and Staphylococcus aureus to study bacterial attachment to the patterned surfaces. In addition, surface wettability was measured by a static contact angle measurement. Results: Contact angles increased with cylinder size and thus hydrophobicity. Despite the difference in wettability, Staphylococcus aureus was not affected by the microstructures, while for Pseudomonas aeruginosa the bacterial load increased with the size of the cylinders, and compared to a flat surface, a reduction in bacteria was observed for one strain on the smallest cylinders. Conclusions: Two-photon lithography allowed rapid and flexible production of microcylinders of different sizes, which affected surface wettability and bacterial load, however, depending on bacterial type and strain. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa belongs to the critical pathogens that represent a global public health problem due to their high rate of resistance as listed by WHO. P. aeruginosa can result in many nosocomial infections especially in individuals with compromised immune systems. Attenuating virulence factors by interference with quorum sensing (QS) systems is a promising approach to treat P. aeruginosa-resistant infections. Thymoquinone is a natural compound isolated from Nigella sativa (black seed) essential oil. In this study, the minimum inhibitory concentration of thymoquinone was detected followed by investigating the antibiofilm and antivirulence activities of the subinhibitory concentration of thymoquinone against P. aeruginosa PAO1. The effect of thymoquinone on the expression of QS genes was assessed by quantitative real-time PCR, and the protective effect of thymoquinone against the pathogenesis of PAO1 in mice was detected by the mouse survival test. Thymoquinone significantly inhibited biofilm, pyocyanin, protease activity, and swarming motility. At the molecular level, thymoquinone markedly downregulated QS genes lasI, lasR, rhlI, and rhlR. Moreover, thymoquinone could protect mice from the pathologic effects of P. aeruginosa increasing mouse survival from 20% to 100%. In conclusion, thymoquinone is a promising natural agent that can be used as an adjunct therapeutic agent with antibiotics to attenuate the pathogenicity of P. aeruginosa. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a major cause of nosocomial infections and the leading cause of chronic lung infections in cystic fibrosis and chronic obstructive pulmonary disease patients. Antibiotic treatment remains challenging because P. aeruginosa is resistant to high concentrations of antibiotics and has a remarkable ability to acquire mutations conferring resistance to multiple groups of antimicrobial agents. Here we report that when P. aeruginosa is plated on ciprofloxacin (cipro) plates, the majority of cipro-resistant (ciproR) colonies observed at and after 48 h of incubation carry mutations in genes related to the Stringent Response (SR). Mutations in one of the major SR components, spoT, were present in approximately 40% of the ciproR isolates. Compared to the wild-type strain, most of these isolates had decreased growth rate, longer lag phase and altered intracellular ppGpp content. Also, 75% of all sequenced mutations were insertions and deletions, with short deletions being the most frequently occurring mutation type. We present evidence that most of the observed mutations are induced on the selective plates in a subpopulation of cells that are not instantly killed by cipro. Our results suggests that the SR may be an important contributor to antibiotic resistance acquisition in P. aeruginosa. [ABSTRACT FROM AUTHOR]

Introduction: Antimicrobial resistance (AMR) is a pressing global health concern, particularly pronounced in low-resource settings. In Ethiopia, the escalating prevalence of carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) poses a substantial threat to public health. Methods: A comprehensive search of databases, including PubMed, Scopus, Embase, Hinari, and Google Scholar, identified relevant studies. Inclusion criteria encompassed observational studies reporting the prevalence of meropenem-resistant P. aeruginosa in Ethiopia. Quality assessment utilized JBI checklists. A random-effects meta-analysis pooled data on study characteristics and prevalence estimates, with subsequent subgroup and sensitivity analyses. Publication bias was assessed graphically and statistically. Results: Out of 433 studies, nineteen, comprising a total sample of 11,131, met inclusion criteria. The pooled prevalence of meropenem-resistant P. aeruginosa was 15% (95% CI: 10–21%). Significant heterogeneity (I2 = 83.6%) was observed, with the number of P. aeruginosa isolates identified as the primary source of heterogeneity (p = 0.127). Subgroup analysis by infection source revealed a higher prevalence in hospital-acquired infections (28%, 95% CI: 10, 46) compared to community settings (6%, 95% CI: 2, 11). Geographic based subgroup analysis indicated the highest prevalence in the Amhara region (23%, 95% CI: 8, 38), followed by Addis Ababa (21%, 95% CI: 11, 32), and lower prevalence in the Oromia region (7%, 95% CI: 4, 19). Wound samples exhibited the highest resistance (25%, 95% CI: 25, 78), while sputum samples showed the lowest prevalence. Publication bias, identified through funnel plot examination and Egger's regression test (p < 0.001), execution of trim and fill analysis resulted in an adjusted pooled prevalence of (3.7%, 95% CI: 2.3, 9.6). Conclusion: The noteworthy prevalence of meropenem resistance among P. aeruginosa isolates in Ethiopia, particularly in healthcare settings, underscores the urgency of implementing strict infection control practices and antibiotic stewardship. Further research is imperative to address and mitigate the challenges posed by antimicrobial resistance in the country. [ABSTRACT FROM AUTHOR]