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Cureus Mar 2024Background Typhoid fever presents a significant challenge in developing nations, exacerbated by the emergence of antibiotic-resistant strains due to widespread...
Background Typhoid fever presents a significant challenge in developing nations, exacerbated by the emergence of antibiotic-resistant strains due to widespread prevalence and overuse of antibiotics. This study seeks to assess the antibiogram profiles of Salmonella species isolated from blood cultures of patients hospitalized at two prominent tertiary care hospitals in Peshawar, Pakistan: Khyber Teaching Hospital (KTH) and Hayatabad Medical Complex (HMC). By examining these profiles, the research aims to provide valuable insights into the evolving landscape of antibiotic resistance in the context of typhoid fever management. Materials and Methods This retrospective cross-sectional study utilized data gathered from two hospitals in Peshawar, KTH and HMC. Cases of enteric fever were identified based on positive blood cultures for Salmonella species. The study encompasses demographic information, seasonal prevalence, and antibiogram profiles of 3,137 cases that were presented between 2017 and 2023. Results Among the total 3,137 cases, males accounted for the majority, comprising 63% (2,044 cases). Particularly notable was the clustering of cases among children and adolescents aged one to 24 years. The incidence peaked during the months of summer and spring, from April to September. In terms of Salmonella Typhi isolates, considerable resistance was noted against first-line antibiotics such as amoxicillin/clavulanate (80.1%), co-trimoxazole/trimethoprim-sulfamethoxazole (66.6%), and chloramphenicol (86.9%), as well as against ceftriaxone (79.7%) and ciprofloxacin (51.6%). Conversely, certain antibiotics displayed higher sensitivity patterns, including meropenem (97.8%), doripenem (99.5%), imipenem (97.7%), ertapenem (96.5%), polymyxin B (99.4%), colistin (98.1%), and tigecycline (97.3%). Despite a limited sample size of 214 specimens, fosfomycin demonstrated a remarkable sensitivity of 93.4%. Sensitivities of amikacin and gentamicin were 90.7% and 81.5%, respectively. However, the sensitivity of azithromycin was concerning, standing at 66.5%. The antibiogram pattern for Salmonella exhibited significant and drastic changes. Conclusion In conclusion, this study sheds light on a higher prevalence of typhoid fever among males, with a notable seasonal peak observed during the summer and spring months. The age group most affected spans from one to 24 years. Salmonella isolates displayed significant resistance to conventional first-line antibiotics, alongside ciprofloxacin and third-generation cephalosporins. Azithromycin exhibited lower sensitivity compared to amikacin, gentamicin, and fosfomycin. The research advocates for the empirical use of amikacin, gentamicin, fosfomycin, and meropenem in the treatment of typhoid fever in Pakistan. Urgent measures, including regular Salmonella antibiogram surveillance, antibiotic stewardship, public health education, and Salmonella vaccination programs, are deemed crucial for primary disease prevention.
PubMed: 38686255
DOI: 10.7759/cureus.57110 -
Infectious Diseases & Clinical... Sep 2023This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes. (Review)
Review
OBJECTIVE
This study aimed to determine the effect of prophylactic use of carbapenems for acute pancreatitis on clinical outcomes.
MATERIALS AND METHODS
It was conducted according to the preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by using the keywords "Pancrea AND carbapenem OR imipenem OR ertapenem OR meropenem OR doripenem." Primer outcomes were mortality, surgical intervention, and pancreatic and non-pancreatic infection. Subgroup analyses were also performed to reduce the risk of bias.
RESULTS
Ten studies with 4038 patients were included in the meta-analyses. While eight of ten were randomized controlled trials, two were observational studies. The prophylactic use of carbapenems had no statistically significant effect on mortality (OR=0.82, 95% CI=0.65-1.04, I²=0%) and surgical intervention. (OR=0.81, 95% CI=0.57-1.17, I²=0%). However, the real impact of prophylaxis on reducing the incidence of mortality and surgical intervention was uncertain due to the insufficient sample size. The prophylactic use of carbapenems was significantly associated with a lower risk of peripancreatic (OR=0.37, 95% CI=0.25-0.55, I²=61%) and non-pancreatic infection risk (OR=0.60, 95% CI=0.46-0.78, I²=65%). The definitions of infection in the articles were not clear, and the diagnostic approach to infection was based on subjective criteria. In addition, there was inadequate collateral damage and safety assessments. In high-quality studies with a low risk of bias, prophylactic carbapenems had no effect on peripancreatic infection (RR=1.54, 95% CI=0.65-3.47, I²=0%) and non-pancreatic infection (RR=0.72, 95% CI=0.48-1.07, I²=0%).
CONCLUSION
Although there is a reduction in the infection risk, routine carbapenem use in acute pancreatitis cases should not be recommended based on current evidence. Cooperation with Infectious Disease specialists and developing diagnostic algorithms are required instead of routine prophylaxis to prevent infection, especially non-pancreatic infection.
PubMed: 38633556
DOI: 10.36519/idcm.2023.239 -
PloS One 2024The emergence and spread of multidrug-resistant pathogens like Pseudomonas aeruginosa are major concerns for public health worldwide. This study aimed to assess the...
The emergence and spread of multidrug-resistant pathogens like Pseudomonas aeruginosa are major concerns for public health worldwide. This study aimed to assess the prevalence of P. aeruginosa in clinical, environmental, and poultry sources in Bangladesh, along with their antibiotic susceptibility and the profiling of β-lactamase and virulence genes using standard molecular and microbiology techniques. We collected 110 samples from five different locations, viz., BAU residential area (BAURA; n = 15), BAU Healthcare Center (BAUHCC; n = 20), BAU Veterinary Teaching Hospital (BAUVTH; n = 22), Poultry Market (PM; n = 30) and Mymensingh Medical College Hospital (MCCH; n = 23). After overnight enrichment in nutrient broth, 89 probable Pseudomonas isolates (80.90%) were screened through selective culture, gram-staining and biochemical tests. Using genus- and species-specific PCR, we confirmed 22 isolates (20.0%) as P. aeruginosa from these samples. Antibiogram profiling revealed that 100.0% P. aeruginosa isolates (n = 22) were multidrug-resistant isolates, showing resistance against Doripenem, Penicillin, Ceftazidime, Cefepime, and Imipenem. Furthermore, resistance to aztreonam was observed in 95.45% isolates. However, P. aeruginosa isolates showed a varying degree of sensitivity against Amikacin, Gentamicin, and Ciprofloxacin. The blaTEM gene was detected in 86.0% isolates, while blaCMY, blaSHV and blaOXA, were detected in 27.0%, 18.0% and 5.0% of the P. aeruginosa isolates, respectively. The algD gene was detected in 32.0% isolates, whereas lasB and exoA genes were identified in 9.0% and 5.0% P. aeruginosa isolates. However, none of the P. aeruginosa isolates harbored exoS gene. Hence, this study provides valuable and novel insights on the resistance and virulence of circulating P. aeruginosa within the clinical, environmental, and poultry environments of Bangladesh. These findings are crucial for understanding the emergence of β-lactamase resistance in P. aeruginosa, highlighting its usefulness in the treatment and control of P. aeruginosa infections in both human and animal populations.
Topics: Humans; Animals; Anti-Bacterial Agents; Pseudomonas aeruginosa; beta-Lactamases; Virulence; Hospitals, Animal; Bangladesh; Poultry; Hospitals, Teaching; Pseudomonas Infections; Microbial Sensitivity Tests
PubMed: 38626002
DOI: 10.1371/journal.pone.0296542 -
Annals of Clinical Microbiology and... Mar 2024Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most appropriate antibiotic to treat S. maltophilia infection is a major challenge.
AIM
The current meta-analysis aimed to investigate the global prevalence of antibiotic resistance among S. maltophilia isolates to the develop more effective therapeutic strategies.
METHOD
A systematic literature search was performed using the appropriate search syntax after searching Pubmed, Embase, Web of Science and Scopus databases (May 2023). Statistical analysis was performed using Pooled and the random effects model in R and the metafor package. A total of 11,438 articles were retrieved. After a thorough evaluation, 289 studies were finally eligible for inclusion in this systematic review and meta-analysis.
RESULT
Present analysis indicated that the highest incidences of resistance were associated with doripenem (97%), cefoxitin (96%), imipenem and cefuroxime (95%), ampicillin (94%), ceftriaxone (92%), aztreonam (91%) and meropenem (90%) which resistance to Carbapenems is intrinsic. The lowest resistance rates were documented for minocycline (3%), cefiderocol (4%). The global resistance rate to TMP-SMX remained constant in two periods before and after 2010 (14.4% vs. 14.6%). A significant increase in resistance to tigecycline and ceftolozane/tazobactam was observed before and after 2010.
CONCLUSIONS
Minocycline and cefiderocol can be considered the preferred treatment options due to low resistance rates, although regional differences in resistance rates to other antibiotics should be considered. The low global prevalence of resistance to TMP-SMX as a first-line treatment for S. maltophilia suggests that it remains an effective treatment option.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Minocycline; Stenotrophomonas maltophilia; Microbial Sensitivity Tests; Anti-Bacterial Agents; Cefiderocol; Drug Resistance, Microbial; Gram-Negative Bacterial Infections
PubMed: 38504262
DOI: 10.1186/s12941-024-00685-4 -
Microbiology Spectrum Apr 2024In 2020, the strain JARB-RN-0044 was isolated from a midstream urine sample of an elderly hospitalized patient in Japan and was highly resistant to carbapenem (i.e.,...
In 2020, the strain JARB-RN-0044 was isolated from a midstream urine sample of an elderly hospitalized patient in Japan and was highly resistant to carbapenem (i.e., imipenem, meropenem, and doripenem). Whole-genome sequencing revealed that the complete genome consists of two replicons, a 3.5-Mb chromosome and a 1.5-Mb large non-chromosomal replicon which has not been reported in and referred to as the "megaplasmid" in this study based on Cluster of Orthologous Group of proteins functional analysis. The strain JARB-RN-0044 harbored two novel OXA-60 and OXA-22 family class D β-lactamase genes and on the megaplasmid. Cloning experiments indicated that recombinant clone expressing gene showed increased minimum inhibitory concentrations (MICs) of imipenem, meropenem, and doripenem, indicating that gene encodes carbapenemase. In contrast, recombinant clone expressing gene showed increased MICs of piperacillin and cefazolin, but not of carbapenem. Interestingly, the 44.6 kb putative prophage region containing genes encoding phage integrase, terminase, head and tail protein was identified in the downstream region of gene, and comparative analysis with some previously reported isolates revealed that the prophage region was unique to strain JARB-RN-0044. The existence of a highly carbapenem-resistant isolate may raise human health concerns in Japan, where the population is rapidly aging.IMPORTANCE is an aerobic non-fermenting Gram-negative rod commonly found in aquatic environments and soil. The bacteria can occasionally cause severe hospital-acquired bloodstream infections in immunocompromised patients and it has been recently recognized as an emerging opportunistic human pathogen. Furthermore, some isolates are resistant to various antimicrobial agents, including β-lactams and aminoglycosides, making antimicrobial therapy challenging and clinically problematic. However, clinical awareness of this pathogen is limited. To our knowledge, in Japan, there has been only one report of a carbapenem-resistant clinical isolate from urine by Suzuki et al. in 2015. In this study, whole-genome sequencing analysis revealed the presence and genetic context of novel and genes on the 1.5 Mb megaplasmid from highly carbapenem-resistant isolate and characterized the overall distribution of functional genes in the chromosome and megaplasmid. Our findings highlight the importance of further attention to isolate in clinical settings.
Topics: Humans; Aged; Carbapenems; Meropenem; Doripenem; Escherichia coli; Japan; beta-Lactamases; Bacterial Proteins; Anti-Bacterial Agents; Imipenem; Microbial Sensitivity Tests; Ralstonia
PubMed: 38483476
DOI: 10.1128/spectrum.03919-23 -
BMC Biotechnology Mar 2024Polymicrobial communities lead to worsen the wound infections, due to mixed biofilms, increased antibiotic resistance, and altered virulence production. Promising...
Polymicrobial communities lead to worsen the wound infections, due to mixed biofilms, increased antibiotic resistance, and altered virulence production. Promising approaches, including enzymes, may overcome the complicated condition of polymicrobial infections. Therefore, this study aimed to investigate Staphopain A-mediated virulence and resistance alteration in an animal model of Staphylococcus aureus and Pseudomonas aeruginosa co-infection. S. aureus and P. aeruginosa were co-cultured on the L-929 cell line and wound infection in an animal model. Then, recombinant staphopain A was purified and used to treat mono- and co-infections. Following the treatment, changes in virulence factors and resistance were investigated through phenotypic methods and RT-PCR. Staphopain A resulted in a notable reduction in the viability of S. aureus and P. aeruginosa. The biofilm formed in the wound infection in both animal model and cell culture was disrupted remarkably. Moreover, the biofilm-encoding genes, quorum sensing regulating genes, and virulence factors (hemolysin and pyocyanin) controlled by QS were down-regulated in both microorganisms. Furthermore, the resistance to vancomycin and doripenem decreased following treatment with staphopain A. According to this study, staphopain A might promote wound healing and cure co-infection. It seems to be a promising agent to combine with antibiotics to overcome hard-to-cure infections.
Topics: Animals; Virulence; Pseudomonas aeruginosa; Staphylococcus aureus; Coinfection; Virulence Factors; Models, Animal; Drug Resistance, Microbial; Wound Infection
PubMed: 38439037
DOI: 10.1186/s12896-024-00840-x -
Veterinary World Nov 2023Antibiotic resistance is a major global health threat. The increasing prevalence of drug-resistant bacteria poses a serious challenge to the effective treatment of...
BACKGROUND AND AIM
Antibiotic resistance is a major global health threat. The increasing prevalence of drug-resistant bacteria poses a serious challenge to the effective treatment of infections in both humans and animals. Water is a major source of human and animal exposure to bacteria, and the presence of drug-resistant bacteria in water could present a severe threat to public health and animal production. This study investigated the presence of drug-resistant bacteria in Lam Pao Dam (LPD) water in Kalasin, Thailand.
MATERIALS AND METHODS
Ampicillin-resistant strains were obtained from LPD water and identified using 16s rDNA sequencing. Antibiotic resistance genes were detected by polymerase chain reaction using specific primers. The presence of antibiotic-resistant bacteria was evaluated using 16s amplicon analysis. The minimum inhibitory concentration (MIC) of strains against antibiotics was determined.
RESULTS
A total of 12 , 4 , and 4 isolates were resistant to ampicillin. Almost all strains harbored and genes, and two strains also harbored the gene. All four strains harbored the gene. The most abundant species in the LPD sample was , followed by and . The MICs of 10 strains against five antibiotics revealed that all strains were resistant to ampicillin but susceptible to meropenem, doripenem, ertapenem, and imipenem.
CONCLUSION
These findings suggest a high prevalence of drug-resistant bacteria in LPD water. This is a cause for concern, as it could spread antibiotic-resistant infections in the community.
PubMed: 38152267
DOI: 10.14202/vetworld.2023.2321-2328 -
Antibiotics (Basel, Switzerland) Dec 2023The emergence of bacteria resistant to beta-lactam/beta-lactamase inhibitor combinations is insufficiently studied, wherein the role of the inoculum effect (IE) in...
Pharmacodynamics of Doripenem Alone and in Combination with Relebactam in an In Vitro Hollow-Fiber Dynamic Model: Emergence of Resistance of Carbapenemase-Producing and the Inoculum Effect.
The emergence of bacteria resistant to beta-lactam/beta-lactamase inhibitor combinations is insufficiently studied, wherein the role of the inoculum effect (IE) in decreased efficacy is unclear. To address these issues, 5-day treatments with doripenem and doripenem/relebactam combination at different ratios of the agents were simulated in a hollow-fiber dynamic model against carbapenemase-producing at standard and high inocula. Minimal inhibitory concentrations (MICs) of doripenem alone and in the presence of relebactam at two inocula were determined. Combination MICs were tested using traditional (fixed relebactam concentration) and pharmacokinetic-based approach (fixed doripenem-to-relebactam concentration ratio equal to the therapeutic 24-h area under the concentration-time curve (AUC) ratio). In all experiments, resistant subpopulations were noted, but combined simulations reduced their numbers. With doripenem, the IE was apparent for both isolates in combined treatments for one strain. The pharmacokinetic-based approach to combination MIC estimation compared to traditional showed stronger correlation between DOSE/MIC and emergence of resistance. These results support (1) the constraint of relebactam combined with doripenem against the emergence of resistance and IE; (2) the applicability of a pharmacokinetic-based approach to estimate carbapenem MICs in the presence of an inhibitor to predict the IE and to describe the patterns of resistance occurrence.
PubMed: 38136739
DOI: 10.3390/antibiotics12121705 -
Journal of Infection in Developing... Nov 2023Increased carbapenem resistance in Klebsiella spp. strains causes high morbidity and mortality. The genes encoded for carbapenemaseare transferrable between different...
INTRODUCTION
Increased carbapenem resistance in Klebsiella spp. strains causes high morbidity and mortality. The genes encoded for carbapenemaseare transferrable between different bacterial species. In the present study, we aimed to investigate carbapenem resistance genes in Klebsiella spp. strains.
METHODOLOGY
Fifty Klebsiella spp. strains were isolated from rectal swabs of patients hospitalized in the neonatal intensive care unit (NICU). All strains were identified with API20E. The minimum inhibitory concentrations (MICs) of carbapenems were determined by the broth dilution method. The major five carbapenem genes (OXA-48, NDM, VIM, KPC, and IMP) were detected by the multiplex real-time PCR method.
RESULTS
It was found that 49 (98%) of the strains were resistant to ertapenem (MIC ≥ 2μg/mL) and imipenem(MIC ≥ 4 μg/mL), and 47 (94%) of the strains were resistant to doripenem (MIC ≥ 4 μg/mL)and meropenem(MIC ≥ 4 μg/mL).NDM was detected in 42%, OXA-48 in 16%, and VIM in one (2%) isolate, and NDM + OXA-48 co-existed in 36% of the isolates. The KPC and IMP genes were not detected.
CONCLUSIONS
NDM and NDM co-existing with OXA-48 were prevalent in the NICU of Istanbul Medical Faculty Hospital. Paying attention to the hand hygiene of healthcare workers, screening of rectal swabs of hospitalized patients for the presence of carbapenem resistance strains, and isolation of infected patients can effectively control the spread of carbapenem-resistant strains.
Topics: Infant, Newborn; Humans; Carbapenems; Anti-Bacterial Agents; Klebsiella; Real-Time Polymerase Chain Reaction; Prevalence; beta-Lactamases; Klebsiella pneumoniae; Microbial Sensitivity Tests; Bacterial Proteins
PubMed: 38064404
DOI: 10.3855/jidc.17892 -
Research Square Sep 2023During head and neck cancer treatment, off-target ionizing radiation damage to the salivary glands commonly causes a permanent loss of secretory function. Due to the...
During head and neck cancer treatment, off-target ionizing radiation damage to the salivary glands commonly causes a permanent loss of secretory function. Due to the resulting decrease in saliva production, patients have trouble eating, speaking and are predisposed to oral infections and tooth decay. While the radioprotective antioxidant drug Amifostine is FDA approved to prevent radiation-induced hyposalivation, it has intolerable side effects that limit its use, motivating the discovery of alternative therapeutics. To address this issue, we previously developed a salivary gland mimetic (SGm) tissue chip platform. Here, we leverage this SGm tissue chip for high-content drug discovery. First, we developed in-chip assays to quantify glutathione and cellular senescence (β-galactosidase), which are biomarkers of radiation damage, and we validated radioprotection using WR-1065, the active form of Amifostine. Other reported radioprotective drugs including Edaravone, Tempol, N-acetylcysteine (NAC), Rapamycin, Ex-Rad, and Palifermin were also tested to validate the ability of the assays to detect cell damage and radioprotection. All of the drugs except NAC and Ex-Rad exhibited robust radioprotection. Next, a Selleck Chemicals library of 438 FDA-approved drugs was screened for radioprotection. We discovered 25 hits, with most of the drugs identified exhibiting mechanisms of action other than antioxidant activity. Hits were down-selected using EC50 values and pharmacokinetic and pharmacodynamic data from the PubChem database. This led us to test Phenylbutazone (anti-inflammatory), Enoxacin (antibiotic), and Doripenem (antibiotic) for in vivo radioprotection in mice using retroductal injections. Results confirm that Phenylbutazone and Enoxacin exhibited radioprotection equivalent to Amifostine. This body of work demonstrates the development and validation of assays using a SGm tissue chip platform for high-content drug screening and the successful in vitro discovery and in vivo validation of novel radioprotective drugs with non-antioxidant primary indications pointing to possible, yet unknown novel mechanisms of radioprotection.
PubMed: 37790388
DOI: 10.21203/rs.3.rs-3246405/v1