Multidrug-resistant Infections Research Articles

Multidrug-Resistant Urinary Tract Infections in Pregnant Patients and Their Association with Adverse Pregnancy Outcomes—A Retrospective Study

Background/Objectives: Multidrug-resistant urinary tract infections (MDR UTIs) constitute an important public health problem, especially in pregnant patients. The aim of this retrospective study was to characterize the bacterial spectrum and the profile of microbial resistance in cases of UTIs occurring in pregnant women, as well as their impact on obstetrical and neonatal outcomes. Methods: A total of 371 pregnant patients with UTIs were included in the analysis and were segregated into the following groups based on the type of bacterial resistance to antibiotics: MDR UTIs (70 patients, group 1), UTIs resistant to one class of antibiotics (108 patients, group 2), UTIs resistant to two classes of antibiotics (102 patients, group 3), and sensitive UTIs (91 patients, group 4). We used descriptive statistics for characterizing and comparing the microbial spectrum and the clinical characteristics of the patients. A multinomial logistic regression model for evaluating the relationship between the type of urinary tract infection and adverse obstetric or neonatal outcomes was employed. Results: In the case of MDR UTIs, the bacterial spectrum mainly included Escherichia coli, Enterococcus faecalis, and Klebsiella species. We found almost universal resistance to ampicillin. Our data confirmed an increased risk of preterm birth, premature rupture of membranes, neonatal respiratory distress syndrome, and neonatal intensive care unit admission for patients with MDR infections. Conclusions: The increased incidence of pathogens resistant to commonly used antibiotic classes in pregnancy suggests the need for the development of local and national protocols that adapt therapeutic and prophylactic regimens to clinical realities.

Cefiderocol in Combating Carbapenem-Resistant Acinetobacter baumannii: Action and Resistance

Acinetobacter baumannii (A. baumannii) has emerged as a prominent multidrug-resistant (MDR) pathogen, significantly complicating treatment strategies due to its formidable resistance mechanisms, particularly against carbapenems. Reduced membrane permeability, active antibiotic efflux, and enzymatic hydrolysis via different β-lactamases are the main resistance mechanisms displayed by A. baumannii, and they are all effective against successful treatment approaches. This means that alternate treatment approaches, such as combination therapy that incorporates beta-lactams, β-lactamase inhibitors, and novel antibiotics like cefiderocol, must be investigated immediately. Cefiderocol, a new catechol-substituted siderophore cephalosporin, improves antibacterial activity by allowing for better bacterial membrane penetration. Due to its unique structure, cefiderocol can more efficiently target and destroy resistant bacteria by using iron transport systems. Through its inhibition of peptidoglycan formation through binding to penicillin-binding proteins (PBPs), cefiderocol avoids conventional resistance pathways and induces bacterial cell lysis. The possibility of resistance development due to β-lactamase synthesis and mutations in PBPs, however, emphasizes the need for continued investigation into cefiderocol’s efficacy in combination treatment regimes. Cefiderocol’s siderophore mimic mechanism is especially important in iron-limited conditions because it can use ferric-siderophore transporters to enter cells. Additionally, its passive diffusion through bacterial porins increases its intracellular concentrations, making it a good option for treating carbapenem-resistant A. baumannii, especially in cases of severe infections and ventilator-associated diseases (IVACs). Cefiderocol may reduce MDR infection morbidity and mortality when combined with customized antimicrobial treatments, but further investigation is needed to improve patient outcomes and address A. baumannii resistance issues.

Enhanced Antibacterial, Anti-Inflammatory, and Antibiofilm Activities of Tryptophan-Substituted Peptides Derived from Cecropin A-Melittin Hybrid Peptide BP100

The emergence of multidrug-resistant pathogens necessitates the development of novel antimicrobial agents. BP100, a short α-helical antimicrobial peptide (AMP) derived from cecropin A and melittin, has shown promise as a potential therapeutic. To enhance its efficacy, we designed and synthesized 16 tryptophan-substituted BP100 analogs based on helical wheel projections. Among these, BP5, BP6, BP8, BP11, and BP13 exhibited 1.5- to 5.5-fold higher antibacterial activity and improved cell selectivity compared to BP100. These analogs demonstrated superior efficacy in suppressing pro-inflammatory cytokine release in LPS-stimulated RAW 264.7 cells and eradicating preformed biofilms of multidrug-resistant Pseudomonas aeruginosa (MDRPA). Additionally, these analogs showed greater resistance to physiological salts and serum compared to BP100. Mechanistic studies revealed that BP100 and its analogs exert their antibacterial effects through membrane disruption, depolarization, and permeabilization. Notably, these analogs showed synergistic antimicrobial activity with ciprofloxacin against MDRPA. Our findings suggest that these tryptophan-substituted BP100 analogs represent promising candidates for combating multidrug-resistant bacterial infections, offering a multifaceted approach through their antibacterial, anti-inflammatory, and antibiofilm activities.

Correction: Zheng et al. Fabrication of Co-Assembly from Berberine and Tannic Acid for Multidrug-Resistant Bacteria Infection Treatment. Pharmaceutics 2023, 15, 1782

In the original publication [...]

The Use of Cefiderocol in Gram-Negative Bacterial Infections at International Medical Center, Jeddah, Saudi Arabia

Background/Objectives: The necessity for ground-breaking treatments for Gram-negative infections is evident. The World Health Organization, the Infectious Diseases Society of America, and the European Commission have highlighted the critical insufficiency of efficient antibiotics, urging pharmaceutical businesses to manufacture new antibiotics. Therefore, developing new antibiotics with broad efficacy against Gram-negative pathogens is essential. Thus, this research aimed to evaluate the safety and effectiveness of cefiderocol in treating multidrug-resistant Gram-negative bacterial infections at the International Medical Center (IMC), Jeddah, Saudi Arabia. Methods: A retrospective analysis was conducted on patients treated from January 2021 to February 2023. Thirteen case groups treated with cefiderocol were compared to twenty control groups treated with other antibiotics. Results: The results indicated no statistically significant differences in ICU stay, comorbidity indices, or mortality rates between the two groups. Cefiderocol showed high clinical and microbiological cure rates, despite the severity of the patients’ conditions. Carbapenem-resistant Klebsiella pneumoniae and difficult-to-treat resistance Pseudomonas aeruginosa were the most prevalent pathogens in the case and control group, respectively. Two patients treated with cefiderocol developed Clostridioides difficile infection, emphasizing the need for close monitoring of potential adverse effects. Conclusions: The results of this study support cefiderocol as a viable alternative for managing serious infections instigated by multidrug-resistant Gram-negative bacteria.

The Use of Ceftazidime–Avibactam in a Pediatric Intensive Care Unit—An Observational Prospective Study

Background/objectives: Infections caused by carbapenem-resistant Enterobacterales (CRE) are progressively increasing in Pediatric Intensive Care Units (PICUs). Its treatment is challenging due to the lack of pediatric trials. CRE infections are associated with significantly poor outcomes, but ceftazidime–avibactam (CAZ-AVI) has been reported to be successful in their treatment. This study aimed to describe the use and outcome of CAZ-AVI in a PICU. Results: Ten patients were included, with 12 episodes of clinical suspicion or confirmed multidrug-resistant (MDR) bacterial infections treated with CAZ-AVI for surgical prophylaxis, suspicion of sepsis, pneumonia, and surgical wound infection. Of these patients, 80% received empirical treatment because of previous MDR bacterial colonization, and 60% were administrated combination therapy with aztreonam for Metallo-β-Lactamases (MBL)strains. No bacteria were resistant to CAZ-AVI. The average duration of the treatment was 3 days when cultures turned negative and 7 days when MDR bacteria were isolated. Methods: This was an observational prospective study of children treated with CAZ-AVI in the PICU of a tertiary hospital in 2022. Epidemiological, clinical, microbiological, and outcome data were collected. Conclusions: The most frequent use of CAZ-AVI in our PICU was the short-term empirical treatment for patients with previous MDR bacterial colonization and clinical suspicion of bacteremia or sepsis. Furthermore, the combination of CAZ-AVI plus aztreonam could be more effective for CRE infections, especially type Ambler class B as MBL strains.

Antibiofilm and antivirulence efficacy of Pleurotus platypus methanolic extract against Staphylococcus aureus through ROS generation and cell membrane disruption

Multi-drug resistance is recognized as a significant worldwide public health concern in the current century. Biofilm formation further exacerbates bacterial resistance to antibacterial medications, host immunological responses, and phagocytosis, resulting in long-lasting chronic illnesses. Investigating natural resources is a very potent approach for developing alternative anti-infective medications to effectively control multi-drug resistant bacterial infections. In this study, a unique mushroom species namely Pleurotus platypus had been discovered from the Terai-Duars region of West Bengal, India. The myco-chemical profiling and preliminary chemical analysis of Pleurotus platypus methanolic extract determined the significant presence of metabolites belonging to several major chemical classes such as flavonoid, alkaloid, triterpenoid, polyphenol, benzoic acids, coumarin, flavone etc. Most intriguingly, the extract possessed effective antibacterial, antibiofilm and antivirulence properties against Staphylococcus aureus and Methicillin resistant Staphylococcus aureus, one of the most notable drug-resistant opportunistic and nosocomial pathogens. Mechanistically, the mushroom extract enhanced the production of Reactive Oxygen Species (ROS) inside the targeted bacteria, causing alterations in membrane potential, damage to the cellular membrane and further release of intracellular DNA, destined to cell death. Moreover, the methanolic extract reported the eradication of pre-existing biofilms from the urinary catheter surface, hinting towards its future application in the related field. To summarize, Pleurotus platypus methanolic extract could be an excellent alternative antibacterial and antibiofilm therapeutic candidate for the effective management of Staphylococcus infections with improved outcome.

Prevalence of carbapenem-resistant Enterobacterales (CRE) in Saudi Arabia: A systematic review and meta-analysis

Antimicrobial resistance is a significant public health issue. In addressing the threat of multidrug resistant bacterial infections, carbapenems have been used. The carbapenem-resistant Enterobacterales (CRE) are, however, rapidly expanding worldwide. Since the issue of CRE is also a problem in Saudi Arabia, the current meta-analysis was performed to comprehensively evaluate the resistance rates to the main carbapenem antibiotics and determine the actual prevalence of CRE in the country. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was followed. Different web databases including PubMed, Scopus, Web of Science, and ScienceDirect were searched for relevant records. Data were extracted, and summary estimates for resistance to carbapenems were calculated using DerSimonian-Laird method of meta-analysis and the random-effects model. From a total of 787 retrieved records, 69 studies were found fully eligible and were included in the final analyses. More than 50 % of all the studies were conducted after 2010, and the most frequently examined members of the Enterobacterales were Escherichia coli and Klebsiella pneumoniae. The pooled prevalence estimate for imipenem resistance was 6.6 % (95 % CI: 4.7–9.2), 9.1 % (95 % CI: 6.7–12.3) for meropenem, and 18.6 % (95 % CI: 11.9–27.9) for ertapenem. High heterogeneity (I2 > 97 %, p < 0.001) was observed for all the estimates. Compared to other regions of the country, there was higher resistance rates in the Al-Qassim and Al-Jouf provinces. Additionally, resistance to ertapenem was as high as 34.2 % in the most recent study period (2021–2024). Proteus spp was the most prevalent CRE (26.2 %). This review highlights an increasing rate of carbapenem resistance among Enterobacterales, emphasizing the need for collaborative efforts to implement strict infection control and prevention measures. Consistent surveillance is indispensable for safeguarding public health, guiding clinical decisions, and strengthening efforts to tackle the challenges of antibiotic resistance.

Development and characterization of antibacterial marine extract-infused cellulose acetate nanofibers as wound dressings for combatting multidrug-resistant wound infections

Wound infections caused by multidrug-resistant bacteria pose a significant challenge globally in healthcare. Traditional wound dressings often lack efficacy against these resilient pathogens, necessitating the exploration of innovative approaches to combat infections and promote wound healing. This study was designed to investigate a novel wound dressing marine extract-infused electrospun cellulose acetate nanofibers (CANF) with particular emphasis on combating multidrug-resistant bacteria. Cellulose acetate solutions were combined with marine extract (Heteroxenia Fuscescens soft coral, H. Fu) before the creation of electrospun nanofibers. The antibacterial activities of H. Fu extract and the prepared nanofiber mats were explored against Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, and Staphylococcus epidermidis. Furthermore, the antibacterial properties of the crude H. Fu extract were directly assessed, showing potent activity against several pathogens. Results displayed that H. Fu extract has a robust antibacterial action against tested bacteria. Different concentrations of H. Fu (0.05 g, 0.1 g, 0.2 g, and 0.3 g) were added to CA solution, and named as H. Fu-1@CANF, H. Fu-2@CANF, H. Fu-3@CANF and H. Fu-4@CANF, respectively. The obtained results from SEM analysis demonstrated the smooth and uniform fibers. As observed, the addition of H. Fu with specific concentrations (0.05 g, 0.1 g, 0.2 g) has no significant impact on the smooth properties of the formed nanofibers. Increasing the concentration of H. Fu (0.3 g) leads to the formation of nanofibers coated with huge beads. FTIR affirmed the existence of H. Fu that blended with CANF. The hydrophilicity of the formed CANF was significantly enhanced thanks to the presence of H. Fu extract. The contact angle values of CANF, H. Fu-1@CANF, H. Fu-2@CANF, and H. Fu-3@CANF were 33.3°, 57.1°, 60.8° and 62.9°, respectively. The mechanical properties in terms of ultimate force (kg) recoded values were 0.89, 0.95, 1.2, 1.3 for CANF, H. Fu-1@CANF, H. Fu-2@CANF and H. Fu-3@CANF, respectively, those of CNF were markedly enhanced when loaded with H. Fu. This study evaluates the antibacterial efficacy of nanofiber mats loaded with H. Fu extract against common cutaneous bacterial pathogens. Four nanofiber samples were tested for their inhibitory impact on bacterial survival counts using the disc diffusion method. Important results from the study include the observation that H. Fu-3@CANF exhibited the largest zones of inhibition (ZOI) with diameters of 35 ± 0.25 mm for P. aeruginosa, 32 ± 0.65 mm for A. baumannii, 28 ± 0.14 mm for S. aureus, and 27.6 ± 0.48 mm for S. epidermidis. Additionally, the H. Fu-2@CANF sample demonstrated strong antibacterial activity, with ZOI diameters of 32 ± 0.56 mm, 29 ± 0.81 mm, 26 ± 0.27 mm, and 25.4 ± 0.28 mm for the respective bacteria. The Microtox® assay further evaluated the toxicity levels of the nanofiber mats, revealing that while all samples exhibited some toxicity, the H. Fu-3@CANF sample had the lowest toxicity profile. These findings highlight the potential of H. Fu-loaded nanofibers, particularly H. Fu-3@CANF, for broad-spectrum antibacterial applications. The study underscores the importance of incorporating bioactive compounds into nanofiber mats to enhance their antimicrobial properties, making them suitable candidates for medical and environmental applications requiring effective bacterial eradication.

Risk Factors for Multidrug Resistance in Patients Infected with Carbapenem-Resistant Klebsiella pneumoniae: A Nomogram.

Our aim was to determine the risk factors for multidrug resistance in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP). The information of 196 patients with Klebsiella pneumoniae infection was collected. The patients were subsequently assigned to the carbapenem-resistant, multidrug-resistant, and non-multidrug-resistant groups. The risk factors for multidrug resistance in CRKP patients were assessed via least absolute shrinkage and selection operator and logistic regression analyses. Moreover, a nomogram was constructed dependent on the identified risk factors, and calibration and decision curves were plotted to detect its accuracy. Length of stay (LOS) [odds ratio (OR) and 95% confidence interval (CI): 4.558 (1.157-17.961), P = 0.030], intensive care unit (ICU) stay within 30 days [OR and 95% CI: 12.643 (3.780-42.293), P < 0.001], Glasgow Coma Scale (GCS) score [OR and 95% CI: 13.569 (2.738-67.236), P = 0.001], fungal infection [OR and 95% CI: 6.398 (1.969-20.785), P = 0.002], and cardiovascular disease (CVD) [OR and 95% CI: 3.871 (1.293-11.592), P = 0.016] were identified as risk factors for multidrug resistance in CRKP patients. The concordance index (C-index) of the constructed nomogram was 0.950 (95% CI: 0.945-0.955). Moreover, decision curve analysis elucidated the nomogram utilization across a wide range of probability thresholds, ranging from 1% to 100%. Finally, internal validation using random data validated the robustness of the predictive model, yielding a C-index of 0.937. The LOS, ICU stay within 30 days, GCS score, fungal infection, and CVD were recognized as risk factors for multidrug resistance in CRKP patients. The constructed nomogram could accurately predict multidrug-resistant CRKP infections in patients.

Intersecting social and environmental determinants of multidrug-resistant urinary tract infections in East Africa beyond antibiotic use

The global health crisis of antibacterial resistance (ABR) poses a particular threat in low-resource settings like East Africa. Interventions for ABR typically target antibiotic use, overlooking the wider set of factors which drive vulnerability and behaviours. In this cross-sectional study, we investigated the joint contribution of behavioural, environmental, socioeconomic, and demographic factors associated with higher risk of multi-drug resistant urinary tract infections (MDR UTIs) in Kenya, Tanzania, and Uganda. We sampled outpatients with UTI symptoms in healthcare facilities and linked their microbiology data with patient, household and community level data. Using bivariate statistics and Bayesian profile regression on a sample of 1610 individuals, we show that individuals with higher risk of MDR UTIs were more likely to have compound and interrelated social and environmental disadvantages: they were on average older, with lower education, had more chronic illness, lived in resource-deprived households, more likely to have contact with animals, and human or animal waste. This suggests that interventions to tackle ABR need to take account of intersectional socio-environmental disadvantage as a priority.

Genomic epidemiology and resistant genes of Acinetobacter baumannii clinical strains in Vietnamese hospitals.

Introduction. Acinetobacter baumannii is a common cause of multidrug-resistant (MDR) nosocomial infections worldwide, including Vietnam.Hypothesis. Analysis of crucial genetic factors may link to epidemiological characteristics and antibiotic resistance of A. baumannii clinical strains in Vietnamese hospitals.Methodology. Fifty-one A. baumannii clinical strains from six different tertiary hospitals in Vietnam were analysed using whole genome sequencing (WGS), between 2017 and 2019.Results. Eleven sequence types (STs) were identified, including four STs reported for the first time in Vietnam based on the PubMLST database and three new STs not previously documented. ST1336, ST1260 and ST575 were found exclusively in Vietnam. These STs were widely distributed in all hospitals in Vietnam, with ST2 and ST571 being the most dominant. Resistant rates to eight antibiotics, belonging to four antibiotic groups, were very high (72.5-94.1 %) with high MIC values, while resistance to colistin was 29.4%. Fifty-one isolates were identified as MDR, with 100% (51/51) isolates carrying antimicrobial-resistant (AMR) genes, and 52 antibiotic-resistant genes were detected among these strains, including β-lactam (22 genes), chloramphenicol (5 genes), lincosamide (2 genes), aminoglycoside (11 genes), rifampicin (1 gene), quinolone (2 genes), sulfonamide and trimethoprim (4 genes) and tetracycline (5 genes) resistance. The most commonly found mobile structures carried partial or complete transposons: ISaba24/ISEc29/ISEc35 contains a series of antibiotic-resistant genes.Conclusion. The WGS results of the 51 strains of A. baumannii provided important information regarding the distribution of STs and associated antibiotic-resistant genes among A. baumannii strains.

Quaternary Ammonium Salt Derivatives of Hyperbranched Polylysine with Enhanced Antibacterial Activity against Multidrug-Resistant Gram-Negative Bacteria.

Multidrug-resistant (MDR) Gram-negative bacteria infections have gradually become a more serious health problem recently, and antibacterial drugs are urgently needed to tackle MDR Gram-negative bacteria. Herein, we synthesized a series of quaternary ammonium salt derivatives of hyperbranched polylysine (HPL-Cm-n) with different alkyl chain lengths (m = 4, 8, 12, 16) and grafting ratios (n = 5.8-21.0) of alkyl quaternary ammonium salts (Cm). HPL-Cm-ns exhibited excellent antibacterial activities against drug-sensitive E. coli and P. aeruginosa, and specifically, HPL-C12-ns were also highly active against MDR E. coli and P. aeruginosa. The cytotoxicity and hemolytic activity of HPL-Cm-ns increased with the increase in the alkyl chain length and the grafting ratio of Cm. The killing study proved that HPL-C12-9.5 had fast killing kinetics and was bactericidal toward both drug-sensitive and MDR E. coli. The mechanistic studies showed that, similar to hyperbranched polylysine (HPL), HPL-C12-9.5 killed bacteria by disrupting the cell membranes and causing leakage of the cytoplasmic contents. HPL-C12-ns might have potential as an antibacterial agent to combat MDR Gram-negative bacteria.

Self-assembly antimicrobial peptide for treatment of multidrug-resistant bacterial infection

The wide-spreading of multidrug resistance poses a significant threat to human and animal health. Although antimicrobial peptides (AMPs) show great potential application, their instability has severely limited their clinical application. Here, self-assembled AMPs composed of multiple modules based on the principle of associating natural marine peptide N6 with ß-sheet-forming peptide were designed. It is noteworthy that one of the designed peptides, FFN could self-assemble into nanoparticles at 35.46 µM and achieve a dynamic transformation from nanoparticles to nanofibers in the presence of bacteria, resulting in a significant increase in stability in trypsin and tissues by 1.72–57.5 times compared to that of N6. Additionally, FFN exhibits a broad spectrum of antibacterial activity against multidrug-resistant (MDR) gram-positive (G+) and gram-negative (G−) bacteria with Minimum inhibitory concentrations (MICs) as low as 2 µM by membrane destruction and complemented by nanofiber capture. In vivo mouse mastitis infection model further confirmed the therapeutic potential and promising biosafety of the self-assembled peptide FFN, which can effectively alleviate mastitis caused by MDR Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and eliminate pathogenic bacteria. In conclusion, the design of peptide-based nanomaterials presents a novel approach for the delivery and clinical translation of AMPs, promoting their application in medicine and animal husbandry.Graphical

Phages ZC01 and ZC03 require type-IV pilus for Pseudomonas aeruginosa infection and have a potential for therapeutic applications.

There has been a growing interest in bacteriophages as therapeutic agents to treat multidrug-resistant bacterial infections. The present work aimed at expanding the microbiological and molecular characterization of lytic phages ZC01 and ZC03 and investigating their efficacy in the control of Pseudomonas aeruginosa infection in an invertebrate animal model. These two phages were previously isolated from composting using P. aeruginosa strain PA14 as the enrichment host and had their genomes sequenced. ZC01 and ZC03 present, respectively, siphovirus and podovirus morphotypes. ZC01 was recently classified into the genus Abidjanvirus, while ZC03 belongs to Zicotriavirus genus of the Schitoviridae N4-like viruses. Through proteomics analysis, we identified virion structural proteins of ZC01 and ZC03, including a large virion-associated RNA polymerase that is characteristic of N4-like viruses, some hypothetical proteins whose annotation should be changed to virion structural proteins and a putative peptidoglycan hydrolase. Phages ZC01 and ZC03 exhibit a limited yet distinct host range, with moderate to high efficiency of plating (EOP) values observed for a few P. aeruginosa clinical isolates. Phage susceptibility assays in PA14 mutant strains point to the type-IV pilus (T4P) as the primary receptor for phages ZC01 and ZC03, and the major pilin (PilAPA14) is the T4P component recognized by these phages. Moreover, both phages significantly increase survival of Galleria mellonella larvae infected with PA14 strain. Taken together, these results underpin the therapeutic potential of these phages to treat infections by P. aeruginosa and lay the groundwork for a more detailed investigation of phage-bacteria-specific recognition mechanisms.IMPORTANCEPhage therapy is gaining increasing interest in cases of difficult-to-treat bacterial human infections, such as carbapenem-resistant Pseudomonas aeruginosa. In this work, we investigated the molecular mechanism underlying the interaction of the lytic phages ZC01 and ZC03 with the highly virulent P. aeruginosa PA14 strain and their efficacy to treat PA14 infection in Galleria mellonella larvae, a commonly used invertebrate model for phage therapy. We depicted the protein composition of ZC01 and ZC03 viral particles and identified pilin A, the major component of type-4 pilus, as the receptor recognized by these phages. Our findings indicate that phages ZC01 and ZC03 may be further used for developing therapies to treat multidrug-resistant P. aeruginosa infections.

Computational prediction of a phage cocktail active against multidrug-resistant bacteria

Background Antibiotic misuse and overuse have contributed to the emergence of multi-drug resistant (MDR) bacteria, posing a serious public health problem across the globe. Phage cocktails, which combine multiple phages, provide an efficient method to combat multidrug-resistant bacterial infections. This study integrated a computational pipeline to design a phage cocktail against the bacterial strains Acinetobacter baumannii AB0057, Klebsiella pneumoniae subsp. pneumoniae HS11286, and Pseudomonas aeruginosa UCBPP-PA14. Methods The whole genome sequences of selected multidrug-resistant bacteria were accessed. Prophage sequences were identified from them which could be expressed to produce viable lytic phages against MDR bacterial strains, thereby reducing the severity of infection. Prophages were annotated for open reading frames (ORFs), putative promoters, virulence factors, transcriptional terminators, ribosomal RNAs, and transfer RNAs. A dot plot was also generated to investigate similar phages and phylogenetic analysis was performed. Results A total of 11 prophages were predicted from the bacterial genomes. About 472 open reading frames were predicted along with 3 transfer RNAs. Additionally, the presence of 754 putative promoters and 281 transcription terminator sequences was also detected. Comparative genomic and phylogenetic analyses provided insight into the diversity, relatedness, and lytic potential of the phages. The final designed phage cocktail consisted of five selected prophages including Acinetobacter baumannii prophages (2759376-2809756) and (3311844-3364667), and Klebsiella pneumoniae prophages (1288317-1338719), (1778306-1808606), and (2280703-2325555). Conclusion The phage cocktail designed in this study might be useful against MDR Acinetobacter baumannii and Klebsiella pneumoniae infections, especially where conventional antibiotics fail. Sequence similarity analysis suggested that the phage cocktail may also be effective against other carbapenemase-producing K. pneumoniae strains.

Carbapenem-Resistant Infections in Neonates and Children in Latin America: A Literature Review.

Carbapenems are broad-spectrum beta-lactam antibiotics that are increasingly being used worldwide to treat multidrug-resistant infections, but since their introduction, carbapenem resistance has emerged. This phenomenon has been well documented in the adult population, but there is a paucity of evidence from the neonatal and pediatric populations. A literature search of carbapenem-resistant infections in Latin American neonates and children was conducted via PubMed/Medline and SCOPUS: 551 titles were screened, and 17 articles were included in the review. The most commonly reported predominant isolate was Klebsiella pneumoniae (11 of 17 studies). Genotypic data were available in 10 of 17 studies, and the KPC gene was the most commonly reported resistance gene. The mortality rate ranged from 13% to 52.6%. Carbapenem-resistant infections are prevalent in children and neonates in Latin America and are associated with high rates of mortality, highlighting the need for enhanced antimicrobial stewardship and surveillance within these populations.

Dispensing of antibiotics in community pharmacies before, during, and after the COVID-19 pandemic

Abstract Background Antibiotic resistance threatens our capability to successfully treat bacteriological infections, becoming a major threat to public health. Therefore, measures must be taken to minimize de incidence of multi-drug resistant bacterial infections. Antimicrobial Stewardship is a systemic healthcare approach devised to foster, enhance, oversee, and assess the judicious application of antimicrobials, aiming to safeguard their efficacy in the future, whilst advocating and safeguarding public health. In the initial phase, a correct diagnosis of antimicrobial utilization is pivotal for the proper implementation of an Antimicrobial Stewardship Program. Methods A cross-sectional study encompassing the Alentejo region, Portugal, with a specific focus on central Alentejo, was conducted to analyze the dispensing of antimicrobials in community pharmacies, alongside the examination of the prescribing locations, before, during, and after the COVID-19 pandemic, from 2019 to 2023. Results The number of antibiotic packages dispensed decreased, as expected, during the COVID-19 pandemic, but returned to pre-pandemic levels after its conclusion. In several prescribing locations, the proportion of cephalosporins and quinolones exceeded the maximum expected value. Conclusions The implementation of an appropriate Antimicrobial Stewardship Program in this region is necessary to ensure the correct prescription of antimicrobials, decreasing the risk that antibiotic resistance pose to public health. Emphasis on the application of the Clinical Practice Guidelines issued by the Portuguese Directorate-General of Health regarding the proper approach to bacterial infections should be intensified so that all prescribing locations exhibit proportions of cephalosporins and quinolones below the maximum expected value. Key messages • Antimicrobial resistance poses a threat to public health. • Stewardship is crucial for appropriately safeguarding public health by reducing antimicrobial resistance emergence.

Polymyxin-B induced bartter-like syndrome: an unusual adverse effect

Introduction and Importance: Bartter syndrome is a rare autosomal recessive disorder affecting renal tubular function, leading to electrolyte and volume homeostasis disturbances. It can also manifest as Bartter-like syndrome, a rare side effect of certain medications. Polymyxin-B, used to treat multidrug-resistant infections, is infrequently associated with BLS, making early recognition crucial to prevent severe electrolyte imbalances. Case Presentation: A 73-year-old female with coronary artery disease, COPD, hyperlipidemia, and other comorbidities presented with fever, respiratory distress, and hypoxia on mechanical ventilation. Initial labs showed leukocytosis, anemia, and normal potassium. Despite broad-spectrum antibiotics, sputum cultures revealed pandrug-resistant Acinetobacter baumannii, sensitive only to Polymyxin-B. After six days of Polymyxin-B, the patient developed fever, hypotension, hypokalemia, hypomagnesemia, and polyuria. Urine studies indicated increased potassium excretion. A diagnosis of Bartter like syndrome was made. Polymyxin-B was discontinued, and the patient’s electrolytes normalized, resolving the polyuria. She was discharged with daily potassium and magnesium supplements. Clinical Discussion: Bartter-like syndrome can result from Polymyxin-B-induced tubular dysfunction, characterized by hypokalemia and hypomagnesemia. Close electrolyte monitoring is essential for patients receiving this antibiotic, particularly in those with complex medical conditions. Early recognition allowed for timely discontinuation of Polymyxin-B, which rapidly reversed the electrolyte disturbances. Conclusion: This case underscores the importance of recognizing Polymyxin-B-induced Bartter-like syndrome. Clinicians should be vigilant for electrolyte disturbances in patients undergoing treatment with Polymyxin-B, ensuring timely interventions to mitigate adverse outcomes.

Assessment of an Antimicrobial Stewardship Program for Enhancing Clinical Knowledge in Neonatal Care Settings With High Antimicrobial Resistance.

Antimicrobial resistance (AMR) is a global problem, which is particularly challenging in developing countries like India. This study attempts to determine the competencies of health care professionals and to update evidence-based policies to address AMR. A survey-based educational interventional study was conducted using a validated structured survey and knowledge questionnaire under 3 domains through an antimicrobial stewardship program. Pooled data were analyzed using SPSS version 16.0. Out of 58 participants, 53 (91%) have observed an increasing trend of multidrug-resistant infections over the last 5years. There is a significant difference between the overall pretest mean scores (8.12±2.10) and posttest mean scores (12.5±1.49) of clinicians' knowledge with a mean difference of 4.38±0.61, 95% CI of 5.003-3.92, t(57)=16.62, P <.001). The antimicrobial stewardship program was effective in improving the competencies of clinical physicians to improve antimicrobial prescribing and reduce AMR. Moreover, improving the knowledge and competencies among health care professionals will minimize neonatal morbidity and mortality.