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1.
Sci Rep ; 14(1): 11430, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38769330

ABSTRACT

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2-3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.


Subject(s)
Anti-Bacterial Agents , Cefixime , Ciprofloxacin , Liver Abscess , Metronidazole , Humans , Ciprofloxacin/administration & dosage , Ciprofloxacin/therapeutic use , Metronidazole/administration & dosage , Metronidazole/therapeutic use , Cefixime/therapeutic use , Cefixime/administration & dosage , Male , Female , Middle Aged , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Liver Abscess/drug therapy , Liver Abscess/microbiology , Treatment Outcome , Double-Blind Method , Drug Therapy, Combination , Drainage , Aged
2.
World J Urol ; 42(1): 221, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587648

ABSTRACT

PURPOSE: Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. RESULTS: We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). CONCLUSION: The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.


Subject(s)
Fosfomycin , Urinary Tract Infections , Humans , Anti-Bacterial Agents/therapeutic use , Fosfomycin/therapeutic use , Nitrofurantoin , Trimethoprim, Sulfamethoxazole Drug Combination , Network Meta-Analysis , Urinary Tract Infections/drug therapy , Ciprofloxacin/therapeutic use , Recurrence
3.
Sex Transm Infect ; 100(3): 173-180, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38575313

ABSTRACT

OBJECTIVES: International travel combined with sex may contribute to dissemination of antimicrobial-resistant (AMR) Neisseria gonorrhoeae (Ng). To assess the role of travel in Ng strain susceptibility, we compared minimum inhibitory concentrations (MICs) for five antibiotics (ie, azithromycin, ceftriaxone, cefotaxime, cefixime and ciprofloxacin) in strains from clients with an exclusively Dutch sexual network and clients with an additional international sexual network. METHODS: From 2013 to 2019, we recorded recent residence of sexual partners of clients (and of their partners) with Ng at the Center for Sexual Health of Amsterdam. We categorised clients as having: (1) exclusively sexual partners residing in the Netherlands ('Dutch only') or (2) at least one partner residing outside the Netherlands. We categorised the country of residence of sexual partners by World Bank/EuroVoc regions. We analysed the difference of log-transformed MIC of Ng strains between categories using linear or hurdle regression for each antibiotic. RESULTS: We included 3367 gay and bisexual men who had sex with men (GBMSM), 516 women and 525 men who exclusively had sex with women (MSW) with Ng. Compared with GBMSM with a 'Dutch only' network, GBMSM with: (1) a Western European network had higher MICs for ceftriaxone (ß=0.19, 95% CI=0.08 to 0.29), cefotaxime (ß=0.19, 95% CI=0.08 to 0.31) and cefixime (ß=0.06, 95% CI=0.001 to 0.11); (2) a Southern European network had a higher MIC for cefixime (ß=0.10, 95% CI=0.02 to 0.17); and (3) a sub-Saharan African network had a lower MIC for ciprofloxacin (ß=-1.79, 95% CI=-2.84 to -0.74). In women and MSW, higher MICs were found for ceftriaxone in clients with a Latin American and Caribbean network (ß=0.26, 95% CI=0.02 to 0.51). CONCLUSIONS: For three cephalosporin antibiotics, we found Ng strains with slightly higher MICs in clients with partner(s) from Europe or Latin America and the Caribbean. International travel might contribute to the spread of Ng with lower susceptibility. More understanding of the emergence of AMR Ng is needed.


Subject(s)
Anti-Infective Agents , Gonorrhea , Sexual Health , Male , Female , Humans , Neisseria gonorrhoeae , Ceftriaxone/pharmacology , Ceftriaxone/therapeutic use , Cefixime/pharmacology , Gonorrhea/drug therapy , Gonorrhea/epidemiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Azithromycin/pharmacology , Cefotaxime/pharmacology , Microbial Sensitivity Tests , Anti-Infective Agents/pharmacology , Drug Resistance, Bacterial
4.
Medicina (Kaunas) ; 60(4)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38674257

ABSTRACT

Background and Objectives: The purpose of this study was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally induced with acetaminophen (AAPh) and potentiated by a ciprofloxacin addition in rats. Material and Methods: The experiment was performed on five animal groups: group 1-control, treated for 6 weeks with normal saline, 1 mL/kg; group 2-AAPh, treated for 6 weeks with AAPh, 100 mg/kg/day; group 3-AAPh + C, treated for 6 weeks with AAPh 100 mg/kg/day and ciprofloxacin 50 mg/kg/day, only in the last 14 days of the experiment; group 4-AAPh + C + Mg, with the same treatment as group 3, but in the last 14 days, MgCl2 10 mg/ kg/day was added; and group 5-AAPh + C + Zn, with the same treatment as group 3, but in the last 14 days, zinc gluconate (ZnG), 10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (p < 0.001 group 2 vs. group 1 for all mentioned parameters). Furthermore, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, at 0.001 < p < 0.01 and 0.01 < p < 0.05, respectively). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days, resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine (0.01 < p < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against the increase in liver enzymes, and a more pronounced protection against the increase in serum urea and creatinine (0.001 < p < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < p < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in the case of ZnG, to a higher extent, especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < p < 0.05 group 5 vs. group 4). Conclusions: This study presents further proof for the beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney's function, and the antioxidant profile improvement has a key role, especially in the case of zinc gluconate.


Subject(s)
Acetaminophen , Ciprofloxacin , Gluconates , Rats, Wistar , Animals , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Rats , Gluconates/pharmacology , Gluconates/therapeutic use , Male , Zinc/pharmacology , Zinc/therapeutic use , Kidney/drug effects , Magnesium/therapeutic use , Magnesium/pharmacology , Liver/drug effects , Liver/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Magnesium Chloride/pharmacology , Magnesium Chloride/therapeutic use , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Drug Synergism
5.
Ann Clin Microbiol Antimicrob ; 23(1): 34, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637789

ABSTRACT

BACKGROUND: Chromobacterium is a genus of fourteen species with validly published names, most often found in soil and waters in tropical and subtropical regions around the world. The most well-known species of the genus, C. violaceum, occasionally causes clinically relevant infections; cases of soft tissue infections with septicemia and fatal outcomes have been described. CASE PRESENTATION: Here, we present a clinical case report of a 79-year-old man from Sweden with a soft-tissue infection and septicemia. The pathogen was identified as a strain of Chromobacterium species, but not C. violaceum. The patient was treated with clindamycin and ciprofloxacin and recovered well. CONCLUSIONS: This case report demonstrates the potential of Chromobacterium species as infectious agents in immunocompetent patients. It also indicates the existence of a novel species.


Subject(s)
Gram-Negative Bacterial Infections , Sepsis , Male , Humans , Aged , Chromobacterium , Sweden , Sepsis/diagnosis , Sepsis/drug therapy , Sepsis/microbiology , Ciprofloxacin/therapeutic use , Clindamycin/therapeutic use , Gram-Negative Bacterial Infections/microbiology
6.
Clin Exp Ophthalmol ; 52(3): 258-275, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38494451

ABSTRACT

Antimicrobial resistance (AMR) is a global public health threat with significant impact on treatment outcomes. The World Health Organization's Global Action Plan on AMR recommended strengthening the evidence base through surveillance programs and research. Comprehensive, timely data on AMR for organisms isolated from ocular infections are needed to guide treatment decisions and inform researchers and microbiologists of emerging trends. This article aims to provide an update on the development of AMR in ocular organisms, AMR in bacterial ocular infections and on AMR stewardship programs globally. The most common ocular pathogens are Pseudomonas aeruginosa, Staphylococcus spp., Streptococcus pneumoniae, and Haemophilus influenzae in ocular infections. A variety of studies and a few surveillance programs worldwide have reported on AMR in these infections over time. Fluoroquinolone resistance has increased particularly in Asia and North America. For conjunctivitis, the ARMOR cumulative study in the USA reported a slight decrease in resistance to ciprofloxacin. For keratitis, resistance to methicillin has remained stable for S. aureus and CoNS, while resistance to ciprofloxacin has decreased for MRSA globally. Methicillin-resistance and multidrug resistance are also emerging, requiring ongoing monitoring. Antimicrobial stewardship (AMS) programmes have a critical role in reducing the threat of AMR and improving treatment outcomes. To be successful AMS must be informed by up-to-date AMR surveillance data. As a profession it is timely for ophthalmology to act to prevent AMR leading to greater visual loss through supporting surveillance programmes and establishing AMS.


Subject(s)
Anti-Bacterial Agents , Eye Infections, Bacterial , Humans , Anti-Bacterial Agents/therapeutic use , Methicillin/therapeutic use , Staphylococcus aureus , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Eye Infections, Bacterial/microbiology , Ciprofloxacin/therapeutic use
7.
Sci Rep ; 14(1): 6947, 2024 03 23.
Article in English | MEDLINE | ID: mdl-38521802

ABSTRACT

Shigellosis remains a common gastrointestinal disease mostly in children < 5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.


Subject(s)
Dysentery, Bacillary , Shigella , Child , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Macrolides/pharmacology , Macrolides/therapeutic use , Drug Resistance, Bacterial/genetics , Azithromycin/pharmacology , Azithromycin/therapeutic use , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Ceftriaxone/pharmacology , Microbial Sensitivity Tests , Protein Synthesis Inhibitors/pharmacology , Plasmids/genetics
8.
BMC Genomics ; 25(1): 287, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38500034

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) remains a significant global health threat particularly impacting low- and middle-income countries (LMICs). These regions often grapple with limited healthcare resources and access to advanced diagnostic tools. Consequently, there is a pressing need for innovative approaches that can enhance AMR surveillance and management. Machine learning (ML) though underutilized in these settings, presents a promising avenue. This study leverages ML models trained on whole-genome sequencing data from England, where such data is more readily available, to predict AMR in E. coli, targeting key antibiotics such as ciprofloxacin, ampicillin, and cefotaxime. A crucial part of our work involved the validation of these models using an independent dataset from Africa, specifically from Uganda, Nigeria, and Tanzania, to ascertain their applicability and effectiveness in LMICs. RESULTS: Model performance varied across antibiotics. The Support Vector Machine excelled in predicting ciprofloxacin resistance (87% accuracy, F1 Score: 0.57), Light Gradient Boosting Machine for cefotaxime (92% accuracy, F1 Score: 0.42), and Gradient Boosting for ampicillin (58% accuracy, F1 Score: 0.66). In validation with data from Africa, Logistic Regression showed high accuracy for ampicillin (94%, F1 Score: 0.97), while Random Forest and Light Gradient Boosting Machine were effective for ciprofloxacin (50% accuracy, F1 Score: 0.56) and cefotaxime (45% accuracy, F1 Score:0.54), respectively. Key mutations associated with AMR were identified for these antibiotics. CONCLUSION: As the threat of AMR continues to rise, the successful application of these models, particularly on genomic datasets from LMICs, signals a promising avenue for improving AMR prediction to support large AMR surveillance programs. This work thus not only expands our current understanding of the genetic underpinnings of AMR but also provides a robust methodological framework that can guide future research and applications in the fight against AMR.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Escherichia coli/genetics , Drug Resistance, Bacterial/genetics , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Ampicillin , Cefotaxime , Machine Learning , Nigeria
9.
Nanomedicine (Lond) ; 19(10): 875-893, 2024 04.
Article in English | MEDLINE | ID: mdl-38530883

ABSTRACT

Aim: To develop a biocompatible conjugated ciprofloxacin-PEG-FeO nanodelivery system with increased efficacy of available therapeutics in a controlled manner. Materials & methods: FeO nanoparticles were synthesized by chemical and biological methods and modified as ciprofloxacin-PEG-FeO nanoformulations. After initial antibacterial and cytotoxicity studies, the effective and biocompatible nanoformulations was further fabricated as nanotherapeutics for in vivo studies in mouse models. Results: Chemically synthesized ciprofloxacin-PEG-FeO nanoformulations demonstrated boosted antibacterial activity against clinically isolated bacterial strains. Nanoformulations were also found to be compatible with baby hamster kidney 21 cells and red blood cells. In in vivo studies, nanotherapeutic showed wound-healing effects with eradication of Staphylococcus aureus infection. Conclusion: The investigations indicate that the developed nanotherapeutic can eradicate localized infections and enhance wound healing with controlled cytotoxicity.


Subject(s)
Antineoplastic Agents , Nanoparticles , Staphylococcal Infections , Cricetinae , Animals , Mice , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Staphylococcal Infections/drug therapy , Antineoplastic Agents/therapeutic use
11.
Can J Urol ; 31(1): 11767-11774, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38401255

ABSTRACT

INTRODUCTION: We evaluate the rate of developing ciprofloxacin resistance in patients undergoing repeat prostate biopsies (PBx), associated risk factors, and impact on complications. MATERIALS AND METHODS: We retrospectively evaluated pre-procedural rectal culture (RCx) data in men undergoing PBx from 1/1/2016 to 1/15/2021. Univariate and multivariate logistic regression were utilized to identify risk factors associated with development of antibiotic resistance. Complication rates were compared between ciprofloxacin-sensitive and ciprofloxacin-resistant patients. RESULTS: A total of 743 men underwent initial RCx. Initial RCx detected ciprofloxacin resistance in 22% of patients. A history of diabetes (p = 0.01), > 2 prior prostate biopsies (p = 0.01), and ciprofloxacin use (p = 0.002) were significant risk factors for ciprofloxacin resistance on initial RCx. The rate of new ciprofloxacin resistance following biopsy with standard ciprofloxacin prophylaxis on 1st and 2nd exposure was 17.2% and 9.1% respectively. The number of biopsy cores, interval antibiotic exposure and interval procedures performed between first and second RCx were not significant predictors of developing ciprofloxacin resistance. Patients who received a non-ciprofloxacin antibiotic between first and second RCx did not develop ciprofloxacin resistance. Antibiotic resistance profile did not significantly affect the rate or type of complications after various prostate procedures. CONCLUSIONS: Serial exposure to standard antibiotic prophylaxis for PBx and associated procedures can lead to development of ciprofloxacin resistance after each subsequent exposure. This carries important implications for serial biopsy and highlights the role for RCx prior to repeat biopsy.


Subject(s)
Anti-Bacterial Agents , Prostate , Male , Humans , Prostate/pathology , Retrospective Studies , Anti-Bacterial Agents/therapeutic use , Biopsy/adverse effects , Biopsy/methods , Ciprofloxacin/therapeutic use , Rectum , Antibiotic Prophylaxis/methods , Drug Resistance, Microbial , Risk Factors
12.
MMWR Morb Mortal Wkly Rep ; 73(5): 99-103, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38329923

ABSTRACT

Meningococcal disease, caused by the bacterium Neisseria meningitidis, is a rare but life-threatening illness that requires prompt antibiotic treatment for patients and antibiotic prophylaxis for their close contacts. Historically, N. meningitidis isolates in the United States have been largely susceptible to the antibiotics recommended for prophylaxis, including ciprofloxacin. Since 2019, however, the number of meningococcal disease cases caused by ciprofloxacin-resistant strains has increased. Antibiotic prophylaxis with ciprofloxacin in areas with ciprofloxacin resistance might result in prophylaxis failure. Health departments should preferentially consider using antibiotics other than ciprofloxacin as prophylaxis for close contacts when both of the following criteria have been met in a local catchment area during a rolling 12-month period: 1) the reporting of two or more invasive meningococcal disease cases caused by ciprofloxacin-resistant strains, and 2) ≥20% of all reported invasive meningococcal disease cases are caused by ciprofloxacin-resistant strains. Other than ciprofloxacin, alternative recommended antibiotic options include rifampin, ceftriaxone, or azithromycin. Ongoing monitoring for antibiotic resistance of meningococcal isolates through surveillance and health care providers' reporting of prophylaxis failures will guide future updates to prophylaxis considerations and recommendations.


Subject(s)
Meningococcal Infections , Neisseria meningitidis , Humans , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Ceftriaxone/therapeutic use , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Meningococcal Infections/drug therapy , Meningococcal Infections/epidemiology , Meningococcal Infections/prevention & control , United States/epidemiology
13.
Int J Biol Macromol ; 262(Pt 1): 130046, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38336334

ABSTRACT

Bacterial sepsis is a mortal syndromic disease characterized by a complex pathophysiology that hinders effective targeted therapy. This study aimed to develop multifunctional, biomimetic and pH-responsive ciprofloxacin-loaded chitosan (CS)/sodium deoxycholic acid (SDC) nanoplexes (CS/SDC) nanoplexes with the ability to target and modulate the TLR4 pathway, activated during sepsis. The formulated nanoplexes were characterized in terms of physicochemical properties, in silico and in vitro potential biological activities. The optimal formulation showed good biocompatibility and stability with appropriate physicochemical parameters. The surface charge changed from negative at pH 7.4 to positive at pH 6.0 accompanied with a significantly faster release of CIP at pH 6.0 compared to 7.4. The biomimicry was elucidated by in silico tools and MST and results confirmed strong binding between the system and TLR4. Furthermore, the system revealed 4- and 2-fold antibacterial enhancement at acidic pH, and 3- and 4-fold better antibiofilm efficacy against Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) respectively, compared to bare CIP. In addition, enhanced bacterial efflux pump inhibition was demonstrated by CS/SDC nanoplexes. Finally, the developed nanosystem showed excellent antioxidant activity against DPPH radicals. Taken together, the study confirmed the multi-functionalities of CS/SDC nanoplexes and their potential benefits in improving bacterial sepsis therapy.


Subject(s)
Chitosan , Methicillin-Resistant Staphylococcus aureus , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Chitosan/chemistry , Biomimetics , Toll-Like Receptor 4 , Anti-Bacterial Agents/chemistry , Hydrogen-Ion Concentration
14.
Transplant Proc ; 56(2): 380-385, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38368126

ABSTRACT

Loss of microbiota diversity has been clearly associated with poor outcomes in the allogeneic hematopoietic stem cell transplantation setting. However, the choice of the optimal antibiotic prophylaxis during the pre-engraftment phase remains unclear. We designed a prospective randomized study to compare our standard-of-care neutropenia prophylaxis (ciprofloxacin) with rifaximin. We enrolled 38 consecutive adult patients who underwent allogeneic hematopoietic stem cell transplantation setting and were randomly assigned to receive ciprofloxacin (20 patients) or rifaximin (18 patients) at day -1. Pretransplant and transplant characteristics did not differ between groups. Cumulative incidence (CI) of acute graft-vs-host disease grade II to IV and moderate/severe chronic graft-vs-host disease was similar in both groups. With a median follow-up of 13.2 months (range, 6.8-30.2) in surviving patients, the 1-year CI of relapse was 20.8% in ciprofloxacin vs 17.8% in rifaximin (P = .616). Importantly, the 1-year CI of treatment-related mortality was significantly reduced in the ciprofloxacin group (10.2% vs 27.8%, P = .032), leading to higher 1-year overall survival (88.9% vs 74.6%, P = .038). In Cox-regression multivariate analysis, antibiotic prophylaxis remained the only predictor of overall survival, independently of donor type, disease risk index, and moderate/severe chronic graft-vs-host disease. Further studies are needed to assess the effects on microbiota diversity and confirm these outcomes.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Neutropenia , Adult , Humans , Rifaximin/adverse effects , Ciprofloxacin/therapeutic use , Prospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control
15.
Lancet Microbe ; 5(3): e226-e234, 2024 03.
Article in English | MEDLINE | ID: mdl-38387472

ABSTRACT

BACKGROUND: Ciprofloxacin is the first-line drug for treating typhoid fever in many countries in Africa with a high disease burden, but the emergence of non-susceptibility poses a challenge to public health programmes. Through enhanced surveillance as part of vaccine evaluation, we investigated the occurrence and potential determinants of ciprofloxacin non-susceptibility in Blantyre, Malawi. METHODS: We conducted systematic surveillance of typhoid fever cases and antibiotic prescription in two health centres in Blantyre, Malawi, between Oct 1, 2016, and Oct 31, 2019, as part of the STRATAA and TyVAC studies. In addition, blood cultures were taken from eligible patients presenting at Queen Elizabeth Central Hospital, Blantyre, as part of routine diagnosis. Inclusion criteria were measured or reported fever, or clinical suspicion of sepsis. Microbiologically, we identified Salmonella enterica serotype Typhi (S Typhi) isolates with a ciprofloxacin non-susceptible phenotype from blood cultures, and used whole-genome sequencing to identify drug-resistance mutations and phylogenetic relationships. We constructed generalised linear regression models to investigate associations between the number of ciprofloxacin prescriptions given per month to study participants and the proportion of S Typhi isolates with quinolone resistance-determining region (QRDR) mutations in the following month. FINDINGS: From 46 989 blood cultures from Queen Elizabeth Central Hospital, 502 S Typhi isolates were obtained, 30 (6%) of which had either decreased ciprofloxacin susceptibility, or ciprofloxacin resistance. From 11 295 blood cultures from STRATAA and TyVAC studies, 241 microbiologically confirmed cases of typhoid fever were identified, and 198 isolates from 195 participants sequenced (mean age 12·8 years [SD 10·2], 53% female, 47% male). Between Oct 1, 2016, and Aug 31, 2019, of 177 typhoid fever cases confirmed by whole-genome sequencing, four (2%) were caused by S Typhi with QRDR mutations, compared with six (33%) of 18 cases between Sept 1 and Oct 31, 2019. This increase was associated with a preceding spike in ciprofloxacin prescriptions. Every additional prescription of ciprofloxacin given to study participants in the preceding month was associated with a 4·2% increase (95% CI 1·8-7·0) in the relative risk of isolating S Typhi with a QRDR mutation (p=0·0008). Phylogenetic analysis showed that S Typhi isolates with QRDR mutations from September and October, 2019, belonged to two distinct subclades encoding two different QRDR mutations, and were closely related (4-10 single-nucleotide polymorphisms) to susceptible S Typhi endemic to Blantyre. INTERPRETATION: We postulate a causal relationship between increased ciprofloxacin prescriptions and an increase in fluoroquinolone non-susceptibility in S Typhi. Decreasing ciprofloxacin use by improving typhoid diagnostics, and reducing typhoid fever cases through the use of an efficacious vaccine, could help to limit the emergence of resistance. FUNDING: Wellcome Trust, Bill & Melinda Gates Foundation, and National Institute for Health and Care Research (UK).


Subject(s)
Typhoid Fever , Typhoid-Paratyphoid Vaccines , Humans , Male , Female , Child , Salmonella typhi/genetics , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Typhoid Fever/drug therapy , Typhoid Fever/epidemiology , Malawi/epidemiology , Phylogeny
16.
Epidemiol Infect ; 152: e19, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38314639

ABSTRACT

C.coli is a significant cause of foodborne gastroenteritis worldwide, with the majority of cases attributed to C.jejuni. Although most clinical laboratories do not typically conduct antimicrobial susceptibility testing for C.coli, the rise in resistant strains has underscored the necessity for such testing and epidemiological surveillance. The current study presents clinical isolate characteristics and demographics of 221 patients with C.coli (coli and jejuni) infections in Northern Israel, between 2015 and 2021. Clinical and demographic data were collected from patient medical records. Susceptibility to erythromycin, tetracycline, ciprofloxacin, and gentamicin was assessed using the standard E-test. No significant correlations were found between bacterial species and patient ethnicity, patient gender, or duration of hospitalization. In contrast, significant differences were found between infecting species and patient age and age subgroup (P < 0.001). Furthermore, erythromycin resistance was observed in only 0.5% of the study population, while resistance to ciprofloxacin, tetracycline, and gentamicin was observed in 95%, 93%, and 2.3% of the population, respectively. The presented study underscores the need for routine surveillance of C.coli antibiotic resistance.


Subject(s)
Campylobacter Infections , Campylobacter jejuni , Humans , Campylobacter Infections/epidemiology , Israel/epidemiology , Microbial Sensitivity Tests , Drug Resistance, Bacterial , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Tetracycline , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Erythromycin/pharmacology , Gentamicins , Demography
17.
Am J Vet Res ; 85(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38422615

ABSTRACT

OBJECTIVE: To determine if a cytochrome (CYP) P450 enzyme inhibitor can maintain therapeutic plasma levels of voriconazole when administered orally. ANIMALS: 11 healthy, common ravens (Corvus corax). METHODS: Birds were randomly assigned to pilot study groups to receive voriconazole orally alone or combined with a CYP inhibitor. Pilot studies with 3 CYP inhibitors launched the main study using ciprofloxacin (20 mg/kg) followed 1 hour later by voriconazole (6 mg/kg) every 12 hours for 14 days. Plasma voriconazole concentrations were measured at various time points by HPLC-MS. The study period lasted from September 2016 to December 2020. RESULTS: The birds failed to maintain therapeutic plasma levels of voriconazole during multidose administration alone or following preadministration with various CYP inhibitors. For the 14-day study period, voriconazole reached a maximum plasma concentration of 2.99 µg/mL with a time-to-peak drug concentration of 1.2 hours following preadministration of ciprofloxacin. One bird was removed from the study due to lethargy, but the other birds completed the study without incident. CLINICAL RELEVANCE: Ciprofloxacin (20 mg/kg) followed by voriconazole (6 mg/kg) maintained the concentration of voriconazole within the recommended therapeutic range of 0.5 to 5 µg/mL without toxicity. Ciprofloxacin prevented the saturable metabolism of voriconazole and maintained these levels for the study duration. This drug combination could be used in the treatment of chronic aspergillosis in the common raven.


Subject(s)
Antifungal Agents , Aspergillosis , Bird Diseases , Ciprofloxacin , Voriconazole , Voriconazole/pharmacokinetics , Voriconazole/therapeutic use , Animals , Ciprofloxacin/pharmacokinetics , Ciprofloxacin/therapeutic use , Pilot Projects , Aspergillosis/veterinary , Aspergillosis/drug therapy , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacokinetics , Bird Diseases/drug therapy , Bird Diseases/microbiology , Cytochrome P-450 Enzyme Inhibitors/pharmacology , Male , Female , Random Allocation , Administration, Oral
18.
Clin Infect Dis ; 78(5): 1222-1231, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38393822

ABSTRACT

BACKGROUND: Tularemia is an important reemerging disease with a multimodal transmission pattern. Treatment outcomes of current recommended antibiotic regimens (including ciprofloxacin and doxycycline) remain unclear. In this retrospective cohort study, we report clinical, laboratory, geographical, and treatment outcomes of laboratory-confirmed tularemia cases over an 11-year period in Northern Sweden. METHODS: Data from reported tularemia cases (aged >10 years at time of study) in Norrbotten county between 2011 and 2021 were collected through review of electronic medical records and participant questionnaires; 415 of 784 accepted participation (52.9%). Of these, 327 were laboratory-confirmed cases (serology and/or polymerase chain reaction). A multivariable logistic regression model was used to investigate variables associated with retreatment. RESULTS: Median age of participants was 54 years (interquartile range [IQR], 41.5-65) and 49.2% were female. Although ulceroglandular tularemia was the predominant form (n = 215, 65.7%), there were several cases of pulmonary tularemia (n = 40; 12.2%). Inflammatory markers were largely nonspecific, with monocytosis frequently observed (n = 36/75; 48%). Tularemia was often misdiagnosed on presentation (n = 158, 48.3%), with 65 (19.9%) receiving initial inappropriate antibiotics and 102 (31.2%) retreated. Persistent lymphadenopathy was infrequent (n = 22, 6.7%), with 10 undergoing surgical interventions. In multivariable analysis of variables associated with retreatment, we highlight differences in time until receiving appropriate antibiotics (8 [IQR, 3.25-20.75] vs 7 [IQR, 4-11.25] days; adjusted P = .076), and doxycycline-based treatment regimen (vs ciprofloxacin; adjusted P = .084), although this was not significant after correction for multiple comparisons. CONCLUSIONS: We comprehensively summarize clinical, laboratory, and treatment outcomes of type B tularemia. Targeting tularemia requires clinical awareness, early diagnosis, and timely commencement of treatment for an appropriate duration.


Subject(s)
Anti-Bacterial Agents , Doxycycline , Tularemia , Humans , Tularemia/drug therapy , Tularemia/diagnosis , Tularemia/epidemiology , Sweden/epidemiology , Female , Middle Aged , Retrospective Studies , Anti-Bacterial Agents/therapeutic use , Male , Adult , Aged , Treatment Outcome , Doxycycline/therapeutic use , Francisella tularensis/isolation & purification , Ciprofloxacin/therapeutic use , Young Adult
19.
J Hosp Infect ; 145: 83-87, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38219833

ABSTRACT

BACKGROUND: Prostate cancer is the most common malignant solid tumour in men aged >70 years and is the second most common cause of death from oncological circumstances. AIM: To evaluate the effect of different short-term prophylactic antibiotic regimens in transrectal prostate biopsy (PB) on the incidence of infectious complications. METHODS: Patients who underwent transrectal ultrasound-guided PB between January 2021 and December 2022 were included in the prospective randomized study. According to the regimen of prophylaxis, patients were randomized into three groups: (1) fosfomycin trometamol 3 g, 3 h before the procedure + ciprofloxacin 500 mg, 2 h before the procedure; (2) fosfomycin trometamol 3 g, 3 h before and 24 h after the procedure; (3) ciprofloxacin 500 mg 12, 2 h before the procedure, and 12 h after the procedure. A rectal swab was performed 1-2 weeks before PB to evaluate the culture findings. Complications were evaluated during follow-up visits within one month after PB. FINDINGS: In the monitored period, 605 PBs were performed, and 544 patients met the inclusion criteria (184, 161, and 199 in groups 1, 2, and 3). Infectious complications occurred in 10 cases (1.83%), namely 3, 4, and 3 according to patient groups. There was no statistically significant difference between the individual groups. None of the patients required hospitalization and all were free of symptoms of sepsis. CONCLUSION: Short-term antibiotic prophylaxis in PB using fosfomycin trometamol, ciprofloxacin, or their combination appears to be effective. Fosfomycin trometamol is a suitable alternative to fluoroquinolone antibiotics.


Subject(s)
Fosfomycin , Prostate , Male , Humans , Prostate/diagnostic imaging , Prostate/pathology , Antibiotic Prophylaxis/methods , Fosfomycin/therapeutic use , Prospective Studies , Tromethamine , Rectum , Biopsy/adverse effects , Biopsy/methods , Ciprofloxacin/therapeutic use , Anti-Bacterial Agents/therapeutic use
20.
Clin Infect Dis ; 78(Suppl 1): S15-S28, 2024 01 31.
Article in English | MEDLINE | ID: mdl-38294108

ABSTRACT

BACKGROUND: Francisella tularensis, the causative agent of tularemia, is endemic throughout the Northern Hemisphere and requires as few as 10 organisms to cause disease, making this potential bioterrorism agent one of the most infectious bacterial pathogens known. Aminoglycosides, tetracyclines, and, more recently, fluoroquinolones are used for treatment of tularemia; however, data on the relative effectiveness of these and other antimicrobial classes are limited. METHODS: Nine databases, including Medline, Global Health, and Embase, were systematically searched for articles containing terms related to tularemia. Articles with case-level data on tularemia diagnosis, antimicrobial treatment, and patient outcome were included. Patient demographics, clinical findings, antimicrobial administration, and outcome (eg, intubation, fatality) were abstracted using a standardized form. RESULTS: Of the 8878 publications identified and screened, 410 articles describing 870 cases from 1993 to 2023 met inclusion criteria. Cases were reported from 35 countries; more than half were from the United States, Turkey, or Spain. The most common clinical forms were ulceroglandular, oropharyngeal, glandular, and pneumonic disease. Among patients treated with aminoglycosides (n = 452 [52%]), fluoroquinolones (n = 339 [39%]), or tetracyclines (n = 419 [48%]), the fatality rate was 0.7%, 0.9%, and 1.2%, respectively. Patients with pneumonic disease who received ciprofloxacin had no fatalities and the lowest rates of thoracentesis/pleural effusion drainage and intubation compared to those who received aminoglycosides and tetracyclines. CONCLUSIONS: Aminoglycosides, fluoroquinolones, and tetracyclines are effective antimicrobials for treatment of tularemia, regardless of clinical manifestation. For pneumonic disease specifically, ciprofloxacin may have slight advantages compared to other antimicrobials.


Subject(s)
Francisella tularensis , Tularemia , Humans , Tularemia/diagnosis , Tularemia/drug therapy , Tularemia/epidemiology , Anti-Bacterial Agents/therapeutic use , Ciprofloxacin/therapeutic use , Aminoglycosides/therapeutic use , Tetracyclines/therapeutic use
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