Search Results (21)

Urogenital infections contribute greatly to both hospital- and community-acquired infections. In Ghana, the prevalence of resistance to commonly used antibiotics is relatively high. This study sought to evaluate the antibiotic sensitivity of bacterial urogenital pathogens from patient samples in a regional and district hospital in the Volta Region of Ghana. A retrospective cross-sectional study was conducted using data obtained between January and December 2023 from Volta Regional Hospital and Margret Marquart Catholic Hospital. Bacteria were isolated from urine, urethral swabs, and vaginal swabs from 204 patients. Data on culture and sensitivity assays performed using the Kirby–Bauer disc diffusion method were extracted and analyzed using WHONET. The most prevalent organisms isolated from the samples from both facilities were Escherichia coli (24.9%), Staphylococcus aureus (21.5%), and Klebsiella oxytoca (8.8%). The isolates were mostly resistant to amoxicillin/clavulanic acid (n = 75, 95% CI [91.8–99.9]), meropenem (n = 61, 95% CI [87.6–99.4]), cefuroxime (n = 54, 95% CI [78.9–96.5]), ampicillin (n = 124, 95% CI [61.2–77.9]), and piperacillin (n = 43, 95% CI [82.9–99.2]). Multidrug-resistant (MDR, 70 (34.1%)), extensively drug-resistant (XDR, 63 (30.7%)), and pandrug-resistant (PDR, 9 (4.3%)) strains of S. aureus, E. coli, and Pseudomonas aeruginosa were identified from the patient samples. The study highlights the presence of high-priority resistant urogenital pathogens of public health significance to varied antibiotic groups. Full article

The objective of this study was to determine the epidemiological, clinical, and laboratory characteristics of newborns with sepsis in northwestern Mexico, identify the microorganisms causing early- and late-onset sepsis, and assess antimicrobial resistance. Additionally, it sought to associate neonatal characteristics with antimicrobial resistance or mortality. A retrospective study was conducted from August 2021 to April 2023, during which 8382 neonatal clinical records were analyzed to collect epidemiological, clinical, and laboratory characteristics, as well as microorganisms isolated from neonates and their antimicrobial resistance profiles. Of these, 314 neonates with sepsis were included. The incidence of neonatal sepsis was 4% (314/8382), and the mortality was 12.7% (40/314); late-onset sepsis (65.3%) was more frequent than early-onset sepsis (34.7%). Staphylococcus epidermidis was the most frequently isolated bacterium in neonates with sepsis (both early- and late-onset). Gram-positive bacteria, such as Staphylococcus hominis and Enterococcus faecium, were associated with early-onset sepsis, whereas fungi, particularly Candida albicans, were associated with late-onset sepsis. Of the microorganisms, 52.6% were multidrug resistant (MDR), 10.8% were extensively drug resistant (XDR), and 5.5% were pan-drug resistant (PDR). Low birth weight, prematurity, cesarean section, mechanical ventilation, tachycardia, and low hemoglobin and platelet levels, among others, were associated with XDR or MDR microorganisms. In contrast, low birth weight, mechanical ventilation, stroke, unexpected delivery, respiratory distress, tachycardia, convulsive crisis, high procalcitonin, urea, and AST/TGO levels, among others, were associated with mortality. The incidence, types of sepsis, antimicrobial resistance, and associations identified in this study will aid in diagnosing neonatal sepsis earlier and may reduce mortality in our region. Full article

Objectives: The aim of this study was to prepare monoclonal antibodies (mAbs) that broadly target Acinetobacter baumannii and protect against infection by multi-drug-resistant (MDR) A. baumannii from different sources. Methods: mAb 8E6 and mAb 1B5 were prepared by sequentially immunizing mice with a sublethal inoculation of three heterogeneous serotypes of pan-drug-resistant (PDR) A. baumannii, ST-208, ST-195, and ST-229. Results: The cross-recognition of heterogeneous bacteria (n = 13) by two mAbs and potential targets was verified, and the in vitro antibacterial efficacy of mAbs was assessed. The median killing rate of mAb 8E6 against A. baumannii in the presence of complement and dHL-60 cells was found to be 61.51%, while that of mAb 1B5 was 41.96%. When only dHL-60 cells were present, the killing rate of mAb 8E6 was 65.73%, while that of mAb 1B5 was 69.93%. We found that mAb 8E6 and mAb 1B5 broadly targeted MDR A. baumannii on the ATP synthase complex and were equipped with an antibacterial killing ability by enhancing the innate immune bacteriolytic effect of ST-208 and ST-195 strains. Both monoclonal antibodies were validated to protect against respiratory infection at 4 and 24 h via enhancing the release of innate immune substances and inflammatory cytokines, effectively shortening the disease period in mice. Conclusions: mAb 8E6 and mAb 1B5 significantly enhanced the opsonization process of phagocytosis against A. baumannii strains prevalent in southern China by targeting ATP synthase antigens thereof, resulting in protective effects in mice. Full article

Acinetobacter baumannii (Ab) has increasingly been identified as a cause of hospital-acquired infections and epidemics. The rise of carbapenem-resistant Acinetobacter baumannii (CRAB) poses significant challenges in treatment. Nosocomial outbreaks linked to CRAΒ A. baumannii strains have been reported worldwide, including in Greece. This study aimed to analyze the molecular epidemiology trends of multidrug-resistant A. baumannii isolates in a tertiary hospital in Athens, Greece. A total of 43 clinical isolates of extensively drug-resistant (XDRAB), pan-drug-resistant (PDRAB), and CRAB were collected from patients suffering from blood infection, hospitalized between 2016 and 2020 at the internal medicine clinics and the ICU. A.baumannii isolates underwent testing for Ambler class B and D carbapenemases and the detection of ISAba1, and were typed, initially, using pulsed-field gel electrophoresis, and, subsequently, using sequence-based typing and multiplex PCR to determine European Clone lineages. The bla_OXA-23 gene accompanied by ISAba1 was prevalent in nearly all A. baumannii isolates, except for one carrying bla_OXA-58. The intrinsic bla_OXA-51-like gene was found in all isolates. No Ambler class B carbapenemases (VIM, NDM) were detected. Isolates were grouped into four PF-clusters and no one-cluster spread was documented, consistent with the absence of outbreak. The study indicated that XDR/PDR-CRAB isolates predominantly produce OXA-23 carbapenemase and belong to European Clone II. Further research is needed to understand the distribution of resistant bacteria and develop effective prevention and control strategies. Full article

In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane–tazobactam, and meropenem–vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including bla_NMD-5 and bla_OXA derivative types, as well as a mutated outer membrane porin protein (OmpK37). Full article

(1) Background: Infections with pan-drug-resistant (PDR) bacteria, such as A. baumannii, are becoming increasingly common, especially in healthcare facilities. In this study, we selected 15 colistin-resistant clinical A. baumannii isolates from a hospital in Beirut, Lebanon, to test combination therapies and determine their sequence types (STs) and the mechanism of colistin resistance using whole-genome sequencing (WGS). (2) Methods: Antimicrobial susceptibility testing via broth microdilution against 12 antimicrobials from different classes and growth rate assays were performed. A checkerboard assay was conducted on PDR isolates using six different antimicrobials, each in combination with colistin. Genomic DNA was extracted from all isolates and subjected to WGS. (3) Results: All isolates were resistant to all tested antimicrobials with the one exception that was susceptible to gentamicin. Combining colistin with either meropenem, ceftolozane–tazobactam, or teicoplanin showed synergistic activity. Sequencing data revealed that 67% of the isolates belonged to Pasteur ST2 and 33% to ST187. Furthermore, these isolates harbored a number of resistance genes, including bla_OXA-23. Mutations in the pmrC gene were behind colistin resistance. (4) Conclusions: With the rise in antimicrobial resistance and the absence of novel antimicrobial production, alternative treatments must be found. The combination therapy results from this study suggest treatment options for PDR ST2 A. baumannii-infected patients. Full article

Introduction: Gram-negative bacteria (GNB) account for about 70% of infections in the intensive care unit (ICU) setting and are associated with significant morbidity and mortality. In recent years, pan-drug resistant (PDR) strains, strains that are not susceptible to any antibiotic, have been emerged and new treatment strategies are required. Results: Fifty eligible patients were recruited in the three groups. A statistically significant reduction in the Sequential Organ Failure Assessment (SOFA) score was observed in the control group on day 4 in comparison to day 0 of VAP (p = 0.005). The Clinical Pulmonary Infection Score (CPIS) was also reduced on day 4 (p = 0.0016) and day 7 in comparison to day 0 (p = 0.001). Patients that received combination therapy, CAZ–AVI + ATM and DCT, presented with a lower SOFA score and CPIS on day 7 in comparison to day 0 (p = 0.0288 and p = 0.037, respectively). No differences in the ΔSOFA score and ΔCPIS were found between the groups. The control group presented with a significantly lower ICU stay and duration of mechanical ventilation (p = 0.03 and p = 0.02, respectively). There was no difference in mortality. Materials and methods: This is a retrospective analysis. This study was conducted in a mixed ICU in the University Hospital of Larissa, Thessaly, Greece during a three-year period (2020-2022). Patients suffering from ventilator associated pneumonia (VAP) due to carbapenem-resistant K. pneumonia (CR-KP) were divided in three different groups: the first one was treated using ceftazidime–avibactam plus aztreonam (CAZ–AVI + ATM group), the second was treated using double carbapenems (DCT group), and the last one (control group) received appropriate therapy since the strain was susceptible in vitro to at least to one antibiotic. Conclusions: Treatment with CAZ–AVI +ATM or DCT may offer a clinical benefit in patients suffering with infections due to PDR K. pneumoniae. Larger studies are required to confirm our findings. Full article

Background: This study aimed to assess the antimicrobial resistance profiles of urinary tract infection (UTI) collected from individuals of various age groups, both male and female. Methods: This study analyzed 266 urine samples from diverse individuals. Midstream urine samples were collected, transported, and processed on a CLED medium within two hours. Bacterial identification was performed based on colony morphology, Gram staining, and biochemical characteristics. The VITEK 2 Compact system (Biomerieux, Marcy-l’Étoile, France) was used for antimicrobial susceptibility testing, ESBL detection, and Carbapenemase detection. Results: Out of 61 significant UTIs in both the male and female patients, 78.69% were caused by Gram-negative bacteria, 11.48% were caused by Gram-positive bacteria, and 9.84% were caused by Candida species. Escherichia coli (37.70%), Klebsiella pneumoniae (26.22%), and Pseudomonas aeruginosa (11.47%) were the most common uropathogens. Tetracycline (88.89%) and ceftriaxone (77.14%) were met with high resistance, while amikacin (89.36%) and colistin (97.30%) were the most effective against both Gram-negative and Gram-positive uropathogens. Colistin susceptibility was exclusively observed in cases of multidrug resistance (MDR) and pan-drug resistance (PDR). Conclusions: This study indicates that Gram-negative bacteria, particularly E. coli, are responsible for a higher number of UTIs compared to Gram-positive uropathogens. Amikacin and colistin were identified as the most effective antibiotics against both Gram-negative and Gram-positive uropathogens. Full article

The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance. Full article

Antibacterial resistance is a renewed public health plague in modern times, and the COVID-19 pandemic has rekindled this problem. Changes in antibiotic prescribing behavior, misinformation, financial hardship, environmental impact, and governance gaps have generally enhanced the misuse and improper access to antibiotics during the COVID-19 pandemic. These determinants, intersected with antibacterial resistance in the current pandemic, may amplify the potential for a future antibacterial resistance pandemic. The occurrence of infections with multidrug-resistant (MDR), extensively drug-resistant (XDR), difficult-to-treat drug-resistant (DTR), carbapenem-resistant (CR), and pan-drug-resistant (PDR) bacteria is still increasing. The aim of this review is to highlight the state of the art of antibacterial resistance worldwide, focusing on the most important pathogens, namely Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae, and their resistance to the most common antibiotics. Full article

Background: Klebsiella pneumoniae is among the most common Gram-negative bacteria isolated to neonatal intensive care units (NICU) and one of the leading causes of morbidity and mortality. The ceftazidime/avibactam (CAZ-AVI) combination is approved for infections caused by aerobic Gram-negative organisms. It is licensed for use in infants over 3 months old. There are no safety and efficacy data regarding the administration of CAZ-AVI to infants younger than 3 months, except for a few case reports. Case presentation: This report describes a severely intoxicated 24-day-old, full-term, male neonate transferred to NICU level III from a secondary maternity hospital due to the deterioration of his general condition. On day four of admission, blood culture revealed the pan-drug-resistant (PDR) K. pneumoniae ss. pneumoniae, susceptible only to CAZ-AVI, which thus represented the only treatment option. Off-label CAZ-AVI was administered intravenously as a salvage therapy. Conclusions: In healthcare settings, treating resistant K. pneumoniae presents serious challenges, especially in NICU patients. The off-label treatment with CAZ-AVI for 17 days was safe and effective in this one-month-old patient. A year later, the patient was healthy with normal cognitive development. Full article

The plant rhizosphere is not only a reservoir of microbes but also a hub of antimicrobial resistance genes. Rhizospheric Bacillus spp. are the potential bio-inoculants with a versatile application in agriculture as bio-fertilizer and bio-fungicide. In the current study, the potential bio-control agent that is the Bacillus species (n = 7) was screened for the antimicrobial resistance pattern to assess their risk before registering them as a bio-inoculant. All of the Bacillus spp. were categorized as multi-drug-resistant (MDR), bacteria but none of them was either pan-drug-resistant (PDR) or extensive-drug-resistant (XDR). The multiple antimicrobial resistance (MAR) index of Bacillus spp. was higher than the critical value (0.2). The Bacillus spp. showed resistance to antimicrobial classes such as β lactam, macrolides, sulfonamides, tetracycline, aminoglycosides, and lincosamide. Various antimicrobial resistance genes, namely VmiR, ImrB, tetL, mphK, ant-6, penp, and bla OXA, associated with different mechanisms of resistance, were also detected in Bacillus spp. The Bacillus spp. also showed stress-tolerance traits such as ACC deaminase and EPS activity except the strains MAZ-117 and FZV-34, respectively. A significant correlation was observed between the PGPR and antimicrobial resistance, which shows that they may have adapted drug-resistance mechanisms to tolerate the environmental stress. These findings suggest that bio-fungicidal Bacillus spp. could be used very carefully on a commercial scale. Full article

Antibiotic resistance, when it comes to bacterial infections, is not a problem that is going to disappear anytime soon. With the lack of larger investment in novel antibiotic research and the ever-growing increase of resistant isolates amongst the ESKAPEE pathogens (Enterobacter cloacae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus sp., and Escherichia coli), it is inevitable that more and more infections caused by extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains will arise. One strategy to counteract the growing threat is to use antibiotic adjuvants, a drug class that on its own lacks significant antibiotic activity, but when mixed with another antibiotic, can potentiate increased killing of bacteria. Antibiotic adjuvants have various mechanisms of action, but polymyxins and polymyxin-like molecules can disrupt the Gram-negative outer membrane and allow other drugs better penetration into the bacterial periplasm and cytoplasm. Previously, we showed that SPR741 had this adjuvant effect with regard to rifampin; however, rifampin is often not used clinically because of easily acquired resistance. To find additional, appropriate clinical partners for SPR741 with respect to pulmonary and wound infections, we investigated tetracyclines and found a previously undocumented synergy with minocycline in vitro and in vivo in murine models of infection. Full article

Carbapenem resistance in Gram-negative bacteria has come into sight as a serious global threat. Carbapenem-resistant Gram-negative pathogens and their main representatives Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are ranked in the highest priority category for new treatments. The worrisome phenomenon of the recent years is the presence of difficult-to-treat resistance (DTR) and pandrug-resistant (PDR) Gram-negative bacteria, characterized as non-susceptible to all conventional antimicrobial agents. DTR and PDR Gram-negative infections are linked with high mortality and associated with nosocomial infections, mainly in critically ill and ICU patients. Therapeutic options for infections caused by DTR and PDR Gram-negative organisms are extremely limited and are based on case reports and series. Herein, the current available knowledge regarding treatment of DTR and PDR infections is discussed. A focal point of the review focuses on salvage treatment, synergistic combinations (double and triple combinations), as well as increased exposure regimen adapted to the MIC of the pathogen. The most available data regarding novel antimicrobials, including novel β-lactam-β-lactamase inhibitor combinations, cefiderocol, and eravacycline as potential agents against DTR and PDR Gram-negative strains in critically ill patients are thoroughly presented. Full article