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1.
BMC Infect Dis ; 23(1): 557, 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37641014

ABSTRACT

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with advanced cirrhosis. Prophylactic Norfloxacin used to be considered effective in SBP prevention, but in recent years its efficacy has been partially compromised by increasing quinolone-resistant bacteria. However, whether the effects of alternative prophylactic regimens are superior to norfloxacin remains controversial. The goal of this study is to compare the effects of norfloxacin with other antibiotics in SBP prophylaxis for cirrhotic patients. METHODS: We systematically searched Pubmed, Embase, and Cochrane Library Databases. Two reviewers independently identified relevant random control trials (RCTs) comparing the role of norfloxacin and other antibiotics in SBP prevention. RESULTS: Eight studies comprising 1043 cirrhotic patients were included in this study. Norfloxacin and alternative antibiotics displayed comparable effects in SBP prophylaxis, survival benefit, overall infection prevention, and safety. Subgroup analyses revealed that rifaximin prophylaxis could reduce the recurrence of SBP with fewer adverse events but failed to improve overall survival compared with norfloxacin. CONCLUSIONS: Other antibiotics are a reasonable alternative to norfloxacin in the prophylaxis of SBP. Rifaximin prophylaxis could be an alternative choose of antibiotic for SBP prevention because of its better protective effect and safety.


Subject(s)
Norfloxacin , Quinolones , Humans , Norfloxacin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Rifaximin , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy
2.
Eur J Clin Microbiol Infect Dis ; 42(4): 481-491, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36820931

ABSTRACT

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.


Subject(s)
Bacterial Infections , Peritonitis , Humans , Norfloxacin/therapeutic use , Cross-Sectional Studies , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Bacterial Infections/microbiology , Anti-Bacterial Agents/therapeutic use , Liver Cirrhosis/complications , Liver Cirrhosis/microbiology , Peritonitis/microbiology , Drug Resistance, Multiple , Antibiotic Prophylaxis/adverse effects
3.
Acta Parasitol ; 68(1): 213-222, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36539677

ABSTRACT

PURPOSE: The in vitro inhibitory effect of two fluroquinolone antibiotics, norfloxacin and ofloxacin, was evaluated in this study on the growth of several Babesia and Theileria parasites with highlighting the bioinformatic analysis for both drugs with the commonly used antibabesial drug, diminazene aceturate (DA), and the recently identified antibabesial drugs, luteolin, and pyronaridine tetraphosphate (PYR). METHODS: The antipiroplasm efficacy of screened fluroquinolones in vitro and in vivo was assessed using a fluorescence-based SYBR Green I assay. Using atom Pair signatures, we investigated the structural similarity between fluroquinolones and the antibabesial drugs. RESULTS: Both fluroquinolones significantly inhibited (P < 0.05) the in vitro growths of Babesia bovis (B. bovis), B. bigemina, B. caballi, and Theileria equi (T. equi) in a dose-dependent manner. The best inhibitory effect for both drugs was observed on the growth of T. equi. Atom Pair fingerprints (APfp) results and AP Tanimoto values revealed that both fluroquinolones, norfloxacin with luteolin, and ofloxacin with PYR, showed the maximum structural similarity (MSS). Two drug interactions findings confirmed the synergetic interaction between these combination therapies against the in vitro growth of B. bovis and T. equi. CONCLUSION: This study helped in discovery novel potent antibabesial combination therapies consist of norfloxacin/ofloxacin, norfloxacin/luteolin, and ofloxacin/PYR.


Subject(s)
Babesia , Babesiosis , Horse Diseases , Theileria , Theileriasis , Animals , Cattle , Horses , Norfloxacin/pharmacology , Norfloxacin/therapeutic use , Ofloxacin/pharmacology , Ofloxacin/therapeutic use , Luteolin/pharmacology , Luteolin/therapeutic use , Babesiosis/parasitology , Theileriasis/parasitology
4.
BMJ ; 379: e069931, 2022 10 04.
Article in English | MEDLINE | ID: mdl-36195324

ABSTRACT

OBJECTIVE: To evaluate the association between initiation of fluoroquinolones and hospital admission or emergency department visit for suicidality. DESIGN: Population based cohort study. SETTING: IBM MarketScan database, USA. PARTICIPANTS: 2 756 268 adults (≥18 years) who initiated an oral fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin, gemifloxacin, ofloxacin, gatifloxacin, norfloxacin, lomefloxacin, besifloxacin) or comparator antibiotic (January 2003 to September 2015) and had at least six months of continuous health plan enrollment and a diagnosis of pneumonia or urinary tract infection (UTI) three days or less before the drug initiation date. Comparator antibiotics were azithromycin in the pneumonia cohort and trimethoprim-sulfamethoxazole in the UTI cohort. Participants were matched 1:1 within each cohort on a propensity score, calculated from a multivariable logistic regression model that included 57 baseline covariates. MAIN OUTCOMES MEASURE: Primary outcome was hospital admission or emergency department visit for suicidal ideation or self-harm within 60 days after treatment initiation. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: The pneumonia cohort included 551 042 individuals, and the UTI cohort included 2 205 526 individuals. During the 60 day follow-up, 181 events were observed in the pneumonia cohort and 966 in the UTI cohort. The adjusted hazard ratios for fluoroquinolones were 1.01 (95% confidence interval 0.76 to 1.36) versus azithromycin in the pneumonia cohort and 1.03 (0.91 to 1.17) versus trimethoprim-sulfamethoxazole in the UTI cohort. Results were consistent across sensitivity analyses and subgroups of sex, age, or history of mental illnesses. CONCLUSION: Initiation of fluoroquinolones was not associated with a substantially increased risk of admission to hospital or emergency department visits for suicidality compared with azithromycin or trimethoprim-sulfamethoxazole.


Subject(s)
Suicide , Urinary Tract Infections , Adult , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Ciprofloxacin/therapeutic use , Cohort Studies , Emergency Service, Hospital , Fluoroquinolones/therapeutic use , Gatifloxacin/therapeutic use , Gemifloxacin , Hospitals , Humans , Levofloxacin/adverse effects , Moxifloxacin/therapeutic use , Norfloxacin/therapeutic use , Retrospective Studies , Suicidal Ideation , Trimethoprim, Sulfamethoxazole Drug Combination , Urinary Tract Infections/drug therapy
5.
J Antimicrob Chemother ; 77(12): 3275-3282, 2022 11 28.
Article in English | MEDLINE | ID: mdl-36173390

ABSTRACT

BACKGROUND: The increased resistance of bacterial pathogens to fluoroquinolones (FQs), such as norfloxacin and ciprofloxacin, supports the need to develop new antibacterial drugs and combination therapies using conventional antibiotics. The LuxS/AI-2 quorum sensing (QS) system can regulate the complex group behaviour of Streptococcus suis and impact its susceptibility to FQs. OBJECTIVES: We investigated the combination of paeoniflorin and norfloxacin as a novel and effective strategy against FQ-resistant S. suis. METHODS: FIC, AI-2 activity assay, real-time RT-PCR and biofilm inhibition assays were performed to investigate the in vitro effect of paeoniflorin combined with norfloxacin. Mouse protection and mouse anti-infection assays were performed to investigate the in vivo effect of paeoniflorin combined with norfloxacin. RESULTS: FIC results showed that paeoniflorin and norfloxacin exert a synergistic bactericidal effect. Evidence was brought that paeoniflorin reduces the S. suis AI-2 activity and significantly down-regulates the transcription of the FQ efflux pump gene. In addition, paeoniflorin can inhibit biofilm formation, thereby promoting the ability of norfloxacin to kill S. suis. Finally, we showed in a mouse model that paeoniflorin in association with norfloxacin is effective to treat S. suis infections. CONCLUSIONS: This study highlighted the inhibitory potential of paeoniflorin on the LuxS/AI-2 QS system of S. suis, and provided evidence that it can inhibit the FQ efflux pump and prevent biofilm formation to cooperate with norfloxacin in the treatment of resistant S. suis-related infections.


Subject(s)
Anti-Bacterial Agents , Monoterpenes , Norfloxacin , Streptococcal Infections , Animals , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Biofilms , Fluoroquinolones/pharmacology , Glucosides/pharmacology , Monoterpenes/pharmacology , Monoterpenes/therapeutic use , Norfloxacin/pharmacology , Norfloxacin/therapeutic use , Streptococcus suis , Streptococcal Infections/drug therapy , Drug Resistance, Bacterial
6.
Life Sci ; 308: 120978, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36122765

ABSTRACT

The increase in bacterial resistance to available antibiotics has driven several researchers to search for new agents with therapeutic properties. Diosgenin is a naturally occurring steroidal saponin that has demonstrated several pharmacological properties. In the present study, we report the antimicrobial activity of diosgenin against the standard and multidrug-resistant bacteria of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, in addition to the efflux pump inhibitory activity against Staphylococcus aureus strains carrying NorA and MepA pumps. For this purpose, the broth microdilution method was used, from which the value of the Minimum Inhibitory Concentration (MIC) was obtained, and this was associated with subinhibitory concentration (MIC/8) with antibiotic of clinical use and ethidium bromide for strains carrier by efflux pump. Diosgenin showed antimicrobial activity for standard S. aureus bacteria and potentiating activity in association with gentamicin and ampicillin for P. aeruginosa multidrug-resistant bacteria, it also showed potentiation in association with norfloxacin against the E. coli strain and gentamicin against the S. aureus strain. Antimicrobial activity against efflux pump-bearing strains revealed that saponin did not interfere with the efflux pump mechanism or intervened antagonistically. Thus, saponin has shown to be very promising against bacterial resistance in association with aminoglycoside, fluoroquinolones and beta-lactam, however additional studies should be carried out to better elucidate the mechanism of action of diosgenin.


Subject(s)
Diosgenin , Saponins , Staphylococcal Infections , Aminoglycosides/therapeutic use , Ampicillin , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins , Diosgenin/pharmacology , Diosgenin/therapeutic use , Escherichia coli/metabolism , Ethidium/pharmacology , Ethidium/therapeutic use , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , Gentamicins , Humans , Microbial Sensitivity Tests , Multidrug Resistance-Associated Proteins , Norfloxacin/pharmacology , Norfloxacin/therapeutic use , Saponins/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcus aureus/metabolism , beta-Lactams/therapeutic use
7.
Rev Assoc Med Bras (1992) ; 68(6): 833-837, 2022.
Article in English | MEDLINE | ID: mdl-35766700

ABSTRACT

OBJECTIVE: Beta-lactams resistance is a major clinical problem in treating pneumonia. This study aimed to detect the extended-spectrum beta-lactamases (ESBL) genes in Klebsiella pneumoniae among patients with community-acquired pneumonia (CAP) in Al-Najaf City, Iraq. METHODS: A total of 511 sputum samples were obtained from all suspected patients with CAP in Al-Najaf City, Iraq, from March 2020 to September 2020. Sputum samples were subjected to microbiological tests. The disk diffusion method was used to test antibiotic sensitivity. Production of ESBLs was identified using phenotypic and genotypic methods. RESULTS: The total prevalence of K. pneumoniae was 31.9% (163/511). Using CHROM agar, 41 (25.2%) isolates were ESBL producers. The imipenem 0.0% (n=0/41) and norfloxacin 0.0% (n=0/41) were the most effective antibiotics. The multiplex polymerase chain reaction showed that 46.3% (n=19/41) of isolates harbored ESBL genes. Out of 19 ESBL producers, 47.4% and 15.8% harbored blaCTX-M and blaSHV, respectively. While blaCTX-M and blaSHV genes were detected in 7 (36.8%) isolates, simultaneously. CONCLUSIONS: The imipenem and norfloxacin can be used in empirical treatment of K. pneumoniae isolates in Iraq. The emergence of K. pneumoniae strains harboring ESBL resistance genes necessitates the development of a regular surveillance program to prevent the spreading of these isolates more in Iraqi health care systems.


Subject(s)
Klebsiella Infections , Pneumonia , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Humans , Imipenem/therapeutic use , Iraq , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests , Norfloxacin/therapeutic use , beta-Lactamases/analysis , beta-Lactamases/genetics , beta-Lactamases/therapeutic use
9.
Am J Gastroenterol ; 117(4): 607-616, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35041634

ABSTRACT

INTRODUCTION: This study aimed to evaluate the role of prophylactic norfloxacin in preventing bacterial infections and its effect on transplant-free survival (TFS) in patients with acute-on-chronic liver failure (ACLF) identified by the Asian Pacific Association for the Study of the Liver criteria. METHODS: Patients with ACLF included in the study were randomly assigned to receive oral norfloxacin 400 mg or matched placebo once daily for 30 days. The incidence of bacterial infections at days 30 and 90 was the primary outcome, whereas TFS at days 30 and 90 was the secondary outcome. RESULTS: A total of 143 patients were included (72 in the norfloxacin and 71 in the placebo groups). Baseline demographics, biochemical variables, and severity scores were similar between the 2 groups. On Kaplan-Meier analysis, the incidence of bacterial infections at day 30 was 18.1% (95% confidence interval [CI], 10-28.9) and 33.8% (95% CI, 23-46) (P = 0.03); and the incidence of bacterial infections at day 90 was 46% (95% CI, 34-58) and 62% (95% CI, 49.67-73.23) in the norfloxacin and placebo groups, respectively (P = 0.02). On Kaplan-Meier analysis, TFS at day 30 was 77.8% (95% CI, 66.43-86.73) and 64.8% (95% CI, 52.54-75.75) in the norfloxacin and placebo groups, respectively (P = 0.084). Similarly, TFS at day 90 was 58.3% (95% CI, 46.11-69.84) and 43.7% (95% CI, 31.91-55.95), respectively (P = 0.058). Thirty percent of infections were caused by multidrug-resistant organisms. More patients developed concomitant candiduria in the norfloxacin group (25%) than in the placebo group (2.63%). DISCUSSION: Primary norfloxacin prophylaxis effectively prevents bacterial infections in patients with ACLF.


Subject(s)
Acute-On-Chronic Liver Failure , Bacterial Infections , Acute-On-Chronic Liver Failure/complications , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Double-Blind Method , Humans , Liver Cirrhosis/complications , Norfloxacin/therapeutic use , Treatment Outcome
10.
Medicina (Kaunas) ; 57(9)2021 Sep 13.
Article in English | MEDLINE | ID: mdl-34577887

ABSTRACT

Background and Objectives: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Antibiotic prophylaxis is effective but can lead to an increased incidence of Clostridioides difficile infection (CDI). The aim of this study was to evaluate the incidence of CDI and the risk factors in cirrhotic patients with a previous episode of SBP receiving norfloxacin as secondary prophylaxis. Materials and Methods: We performed a prospective, cohort study including patients with liver cirrhosis and SBP, successfully treated over a 2-year period in a tertiary university hospital. All the patients received secondary prophylaxis for SBP with norfloxacin 400 mg/day. Results: There were 122 patients with liver cirrhosis and SBP included (mean age 57.5 ± 10.8 years, 65.5% males). Alcoholic cirrhosis was the major etiology accounting for 63.1% of cases. The mean MELD score was 19.7 ± 6.1. Twenty-three (18.8%) of all patients developed CDI during follow-up, corresponding to an incidence of 24.8 cases per 10,000 person-years. The multivariate Cox regression analysis demonstrated that alcoholic LC etiology (HR 1.40, 95% CI 1.104-2.441, p = 0.029) and Child-Pugh C class (HR 2.50, 95% CI 1.257-3.850, p = 0.034) were independent risk factors for CDI development during norfloxacin secondary prophylaxis. The development of CDI did not influence the mortality rates in cirrhotic patients with SBP receiving norfloxacin. Conclusions: Cirrhotic patients with SBP and Child-Pugh C class and alcoholic liver cirrhosis had a higher risk of developing Clostridioides difficile infection during norfloxacin secondary prophylaxis. In patients with alcoholic Child-Pugh C class liver cirrhosis, alternative prophylaxis should be evaluated as SBP secondary prophylaxis.


Subject(s)
Bacterial Infections , Peritonitis , Aged , Bacterial Infections/complications , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Clostridioides , Cohort Studies , Female , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/epidemiology , Male , Middle Aged , Norfloxacin/therapeutic use , Peritonitis/drug therapy , Peritonitis/epidemiology , Peritonitis/etiology , Prospective Studies
11.
PLoS One ; 16(9): e0257004, 2021.
Article in English | MEDLINE | ID: mdl-34534230

ABSTRACT

AIM: To investigate the epidemiology of S. aureus and MRSA nasal carriage among people with diabetes at the Korle Bu Teaching Hospital in Accra, including the prevalence, predictors of carriage, and antibiotic resistance. METHODOLOGY: This study was cross-sectional, involving 300 diabetes patients and 106 non-diabetic individuals. Swab specimens of the nares were obtained from the participants and bacteriologically-cultured. Identification and characterization of S. aureus and MRSA were based on standard bacteriological methods; antimicrobial susceptibility testing was by the Kirby-Bauer method. RESULTS: The prevalence of staphylococcal carriage, the diabetes group relative to the non-diabetes group, were 31.0% and 10.4% (S. aureus), and 3.3% and 0.0% (MRSA). Presence of diabetes predisposed to S. aureus carriage, but not MRSA nor coagulase-negative staphylococci (CoNS) carriage (OR = 3.88; p < 0.0001). Colonization with CoNS was protective of S. aureus (OR = 0.039, p < 0.001) and MRSA (OR = 0.115, p = 0.043) colonization among the diabetics. The antimicrobial resistance patterns recorded among the S. aureus isolated from the diabetic individuals relative to the non-diabetics were as follows: penicillin (95% vs. 91%), tetracycline (37% vs. 27%), cotrimoxazole (30% vs. 36%), erythromycin (17% vs. 0%), norfloxacin (13% vs. 0%), clindamycin (12% vs. 0%), gentamicin (9% vs. 0%), fusidic acid (10% vs. 9%), linezolid (4% vs. 0%), and rifampicin (5% vs. 0%). The proportion of multidrug resistant S. aureus was 41% (n = 38) in the diabetes group and 0% in the non-diabetes group; this difference was statistically significant (p = 0.01). CONCLUSIONS: The presence of diabetes predisposed the participants to S. aureus carriage by almost four folds, but not MRSA carriage. Colonization with CoNS was protective of S. aureus and MRSA carriage in the diabetes group. Finally, linezolid remains a good therapeutic agent for anti-MRSA therapy.


Subject(s)
Diabetes Complications/microbiology , Diabetes Mellitus/microbiology , Drug Resistance, Multiple, Bacterial , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/microbiology , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , Carrier State , Clindamycin/therapeutic use , Cross-Sectional Studies , Diabetes Complications/diagnosis , Diabetes Complications/drug therapy , Diabetes Mellitus/diagnosis , Diabetes Mellitus/drug therapy , Erythromycin/therapeutic use , Female , Fusidic Acid/therapeutic use , Gentamicins/therapeutic use , Humans , Linezolid/therapeutic use , Male , Methicillin-Resistant Staphylococcus aureus/growth & development , Microbial Sensitivity Tests , Middle Aged , Nasal Cavity/microbiology , Norfloxacin/therapeutic use , Penicillins/therapeutic use , Rifampin/therapeutic use , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Tetracycline/therapeutic use , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
12.
J Bioenerg Biomembr ; 53(4): 489-498, 2021 08.
Article in English | MEDLINE | ID: mdl-34159523

ABSTRACT

Undue exposure to antimicrobials has led to the acquisition and development of sophisticated bacterial resistance mechanisms, such as efflux pumps, which are able to expel or reduce the intracellular concentration of various antibiotics, making them ineffective. Therefore, inhibiting this mechanism is a promising way to minimize the phenomenon of resistance in bacteria. In this sense, the present study sought to evaluate the activity of the Carvacrol (CAR) and Thymol (THY) terpenes as possible Efflux Pump Inhibitors (EPIs), by determining the Minimum Inhibitory Concentration (MIC) and the association of these compounds in subinhibitory concentrations with the antibiotic Norfloxacin and with Ethidium Bromide (EtBr) against strains SA-1199 (wild-type) and SA-1199B (overexpresses NorA) of Staphylococcus aureus. In order to verify the interaction of the terpenes with the NorA efflux protein, an in silico molecular modeling study was carried out. The assays used to obtain the MIC of CAR and THY were performed by broth microdilution, while the Efflux Pump inhibitory test was performed by the MIC modification method of the antibiotic Norfloxacin and EtBr. docking was performed using the Molegro Virtual Docker (MVD) program. The results of the study revealed that CAR and THY have moderate bacterial activity and are capable of reducing the MIC of Norfloxacin antibiotic and EtBr in strains of S. aureus carrying the NorA efflux pump. The docking results showed that these terpenes act as possible competitive NorA inhibitors and can be investigated as adjuvants in combined therapies aimed at reducing antibiotic resistance.


Subject(s)
Cymenes/therapeutic use , Multidrug Resistance-Associated Proteins/drug effects , Norfloxacin/therapeutic use , Staphylococcus aureus/drug effects , Thymol/therapeutic use , Cymenes/pharmacology , Norfloxacin/pharmacology , Thymol/pharmacology
14.
Mar Drugs ; 18(12)2020 Dec 17.
Article in English | MEDLINE | ID: mdl-33348729

ABSTRACT

Edwardsiella tarda can cause fatal gastro-/extraintestinal diseases in fish and humans. Overuse of antibiotics has led to antibiotic resistance and contamination in the environment, which highlights the need to find new antimicrobial agents. In this study, the marine peptide-N6 was amidated at its C-terminus to generate N6NH2. The antibacterial activity of N6 and N6NH2 against E. tarda was evaluated in vitro and in vivo; their stability, toxicity and mode of action were also determined. Minimal inhibitory concentrations (MICs) of N6 and N6NH2 against E. tarda were 1.29-3.2 µM. Both N6 and N6NH2 killed bacteria by destroying the cell membrane of E. tarda and binding to lipopolysaccharide (LPS) and genomic DNA. In contrast with N6, N6NH2 improved the stability toward trypsin, reduced hemolysis (by 0.19% at a concentration of 256 µg/mL) and enhanced the ability to penetrate the bacterial outer and inner membrane. In the model of fish peritonitis caused by E. tarda, superior to norfloxacin, N6NH2 improved the survival rate of fish, reduced the bacterial load on the organs, alleviated the organ injury and regulated the immunity of the liver and kidney. These data suggest that the marine peptide N6NH2 may be a candidate for novel antimicrobial agents against E. tarda infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Edwardsiella tarda/drug effects , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/virology , Fish Diseases/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Antimicrobial Cationic Peptides/chemistry , Cell Membrane/drug effects , Enterobacteriaceae Infections/microbiology , Fish Diseases/microbiology , Fish Diseases/pathology , Fish Proteins , Kidney/pathology , Liver/pathology , Microbial Sensitivity Tests , Norfloxacin/therapeutic use , Peritonitis/drug therapy , Peritonitis/etiology , Structure-Activity Relationship , Survival Analysis
15.
Pan Afr Med J ; 37: 47, 2020.
Article in English | MEDLINE | ID: mdl-33209174

ABSTRACT

SARS-CoV-2 has created a global public health emergency with significant mortality and morbidity for people living with HIV (PLWH). Preliminary data reveals persons with immune-compromised status are at risk of developing adverse clinical outcomes from SARS-CoV-2. We aimed to characterise clinical outcomes of HIV patients co-infected with SARS-CoV-2 infection in Nasarawa State, North Central Nigeria. We followed four (4) hospitalised HIV patients that tested positive to SARS-CoV-2 in Nasarawa State and characterised their laboratory findings and clinical outcomes. The consent of the cases was sought and they agreed that their clinical data be published. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 nucleic acid were performed using nasopharyngeal swabs (novel coronavirus PCR fluorescence diagnostic kit, BioGerm medical biotechnology) at the Nigeria Centre for Disease Control (NCDC) in Abuja, Nigeria. Our study reveals mild clinical outcome among HIV patients with SARS-CoV-2 co-infection. There is need for a syndemic framework to be used to conceptualise SARS-CoV-2 impact among HIV patients and an urgent need to strengthen healthcare programmes within Nigeria.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Betacoronavirus , Coinfection/drug therapy , Coronavirus Infections/drug therapy , HIV Infections/drug therapy , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome , Sex Workers , Antiviral Agents/therapeutic use , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Female , Glucocorticoids/therapeutic use , Humans , Methylprednisolone/therapeutic use , Nigeria , Norfloxacin/therapeutic use , Pandemics , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , gamma-Globulins/therapeutic use
16.
Clin Transl Gastroenterol ; 11(8): e00223, 2020 08.
Article in English | MEDLINE | ID: mdl-32955202

ABSTRACT

INTRODUCTION: With the emergence of multidrug-resistant organisms, the efficacy of antibiotic prophylaxis to prevent spontaneous bacterial peritonitis (SBP) has been debated. The aim of this study was to assess factors impacting effectiveness of SBP prophylaxis. METHODS: We searched PubMed, Embase, and the Cochrane Registry from inception to May 2019 to identify randomized controlled trials of patients with liver cirrhosis that assessed SBP occurrence/recurrence during antibiotic prophylaxis with the common antibiotic agents. Network meta-analysis was performed, pooling data with regard to incidence rate ratios (IRRs) of SBP, death, or extraperitoneal infections. RESULTS: Overall, 1,626 patients in 12 randomized controlled trials were included. During primary prophylaxis, the incidence rate of SBP and death in the norfloxacin-treated patients was 0.117 and 0.438 per patient-year, respectively, and IRRs of placebo vs norfloxacin were significantly higher (IRR 5.35, 95% confidence interval 1.99-14.38, P = 0.0009 for SBP and IRR 2.04, 95% confidence interval 1.20-3.44, P = 0.008 for death). The efficacy of norfloxacin to prevent SBP, but not death, decreased over time (annual percent change from 1992 to 2015 8.2%, P = 0.019), The positive treatment effect was lower in studies including patients with increased ascites protein (P = 0.021) or exceedingly high serum bilirubin (P = 0.012) levels. Norfloxacin was not superior to other antibiotics. The incidence rate of SBP was 2.5-fold higher in patients treated with norfloxacin as secondary compared with primary prophylaxis. No significant differences between treatment designs were observed in secondary prophylaxis. DISCUSSION: Norfloxacin remained superior to placebo in preventing SBP, yet the efficacy to prevent SBP, not death, decreased over time. Further studies to understand this phenomenon are urgently needed.


Subject(s)
Antibiotic Prophylaxis/methods , Bacterial Infections/epidemiology , Liver Cirrhosis/complications , Norfloxacin/therapeutic use , Peritonitis/epidemiology , Bacterial Infections/immunology , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , Drug Resistance, Multiple, Bacterial , Humans , Incidence , Liver Cirrhosis/immunology , Liver Cirrhosis/mortality , Peritonitis/immunology , Peritonitis/microbiology , Peritonitis/prevention & control , Randomized Controlled Trials as Topic , Survival Analysis , Treatment Outcome
17.
Article in English | MEDLINE | ID: mdl-31921416

ABSTRACT

Background: Misuse of antibiotics in food animals contributes to an increase of antibiotic resistant bacteria transmitting to humans. China is the largest producer and user of antibiotics in the world, of which animals share more than half of the total consumption. This study aimed to explore Chinese farmer's practice of antibiotic use and the factors associated with their use. Methods: In this cross-sectional survey, we interviewed farmers from 88 chicken farms in northwestern China. We defined two kinds of misuse: 1) using antibiotics in the Chinese prohibited list, and 2) using antibiotics within the recommended withdrawal period. Factor analysis was used to select farmers' knowledge variables and multinomial logistic regression was used to determine factors associated with antibiotic misuse. Results: All the participating farmers used antibiotics on their farms. Amoxicillin was the most common antibiotic used (76.5%), followed by norfloxacin, ofloxacin, ceftriaxone and oxytetracycline. 75% of farmers used antibiotics in the prohibited list while 14.8% continued to use antibiotics during the withdrawal period. Hierarchical cluster analysis revealed three patterns of antibiotic use: 1) excessive use of non-prohibited and prohibited antibiotics or an excessive user, 2) low use of a few types of non-prohibited and moderate use of prohibited antibiotics or a low user, 3) multiple use of a variety (≥ 7 types) of non-prohibited and prohibited antibiotics or a moderate user. Farmers from medium size, family-based farms, those with a low education level and low income were more likely to misuse antibiotics. Prior formal agricultural training was associated with reducing multiple types of antibiotic use. There was a huge gap between policy and reinforcement causing antibiotic misuse in the study community. Conclusion: Antibiotics are commonly used on chicken farms; misuse of antibiotics is high; improvement in farm sanitation, education on antibiotic use for farmers and veterinarians/pharmacists and enforcement of the regulations may reduce antibiotic use on chicken farms in China.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Misuse/statistics & numerical data , Health Knowledge, Attitudes, Practice , Adult , Animals , Ceftriaxone/therapeutic use , Chickens , China , Cross-Sectional Studies , Drug Misuse/prevention & control , Farms , Female , Health Policy , Humans , Logistic Models , Male , Middle Aged , Norfloxacin/therapeutic use , Ofloxacin/therapeutic use , One Health , Oxytetracycline/therapeutic use , Socioeconomic Factors , Surveys and Questionnaires , Young Adult
18.
Skinmed ; 18(6): 374-377, 2020.
Article in English | MEDLINE | ID: mdl-33397569

ABSTRACT

A 60-year-old cachexic man visited the dermatology outpatient department with fluid-filled lesions on much of his body. He had an intermittent high-grade fever, diarrhea, and vomiting for the past 2 months associated with weight loss and decreased appetite. He admitted to having taken norfloxacin 400 mg twice daily for 3 days for diarrhea, 5 days prior to the onset of the lesions. Physical examination revealed pallor and significant lymphadenopathy (cervical, axillary, and inguinal), and his body mass index (BMI) was 17.67. There were generalized, bizarre-shaped, discrete, as well as coalescing, vesicles and bullae over a diffusely erythematous skin. Characteristic "string of pearls morphology" could be seen over the trunk (Figure 1A and 1B). The trunk exhibited sheets of skin peeling with underlying erosions and Nikolsky sign was positive (Figure 1C), although there was no cutaneous tenderness or mucosal involvement. A Tzanck smear revealed the presence of neutrophils and eosinophils but no acantholytic cells. There was moderate hepatomegaly (7 cm below the costal margins).


Subject(s)
Anti-Infective Agents/adverse effects , Linear IgA Bullous Dermatosis/blood , Linear IgA Bullous Dermatosis/diagnosis , Norfloxacin/adverse effects , Anti-Infective Agents/therapeutic use , Humans , Male , Middle Aged , Norfloxacin/therapeutic use
19.
Clin Transl Gastroenterol ; 10(10): e00078, 2019 10.
Article in English | MEDLINE | ID: mdl-31584459

ABSTRACT

Small intestinal bacterial overgrowth (SIBO) is a common, yet underrecognized, problem. Its prevalence is unknown because SIBO requires diagnostic testing. Although abdominal bloating, gas, distension, and diarrhea are common symptoms, they do not predict positive diagnosis. Predisposing factors include proton-pump inhibitors, opioids, gastric bypass, colectomy, and dysmotility. Small bowel aspirate/culture with growth of 10-10 cfu/mL is generally accepted as the "best diagnostic method," but it is invasive. Glucose or lactulose breath testing is noninvasive but an indirect method that requires further standardization and validation for SIBO. Treatment, usually with antibiotics, aims to provide symptom relief through eradication of bacteria in the small intestine. Limited numbers of controlled studies have shown systemic antibiotics (norfloxacin and metronidazole) to be efficacious. However, 15 studies have shown rifaximin, a nonsystemic antibiotic, to be effective against SIBO and well tolerated. Through improved awareness and scientific rigor, the SIBO landscape is poised for transformation.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Blind Loop Syndrome/diagnosis , Gastrointestinal Microbiome/drug effects , Intestinal Mucosa/microbiology , Intestine, Small/microbiology , Age Factors , Bacteria/drug effects , Bacteria/isolation & purification , Blind Loop Syndrome/epidemiology , Blind Loop Syndrome/etiology , Blind Loop Syndrome/therapy , Breath Tests , Clinical Trials as Topic , Colectomy/adverse effects , Female , Food, Formulated , Humans , Intestinal Mucosa/drug effects , Intestine, Small/drug effects , Male , Metronidazole/therapeutic use , Microbiological Techniques , Norfloxacin/therapeutic use , Prevalence , Probiotics/administration & dosage , Proton Pump Inhibitors/adverse effects , Rifaximin/therapeutic use , Risk Factors , Sex Factors , Treatment Outcome
20.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2914-2925, 2019 Jul.
Article in Chinese | MEDLINE | ID: mdl-31602833

ABSTRACT

To systematically review the efficacy and safety of Huoxiang Zhengqi Pills combined with Western medicine in the treatment of acute gastroenteritis. Four Chinese databases( CNKI,VIP,Wan Fang,Sino Med) and three English databases( Cochrane Library,Medline,EMbase) were systematically and comprehensively searched from the database establishment to April 2019 to collect the randomized controlled trials( RCTs) about the treatment of acute gastroenteritis with Huoxiang Zhengqi Pills combined with Western medicine. Two investigators independently performed literature screening,data extraction and bias risk assessment. Rev Man 5. 3 software was used for data analysis. A total of 316 articles were retrieved and finally 44 studies were included in this study,involving 4153 patients. The overall quality of the included studies was generally low. Meta-analysis results showed that in the total clinical effective rate,Huoxiang Zhengqi Pills combined with conventional treatment or norfloxacin tablets was superior to conventional treatment or norfloxacin tablets alone. In terms of the time for improving clinical symptoms,Huoxiang Zhengqi Pills combined with conventional treatment or norfloxacin tablets could better relieve fever than conventional treatment or norfloxacin tablets alone. In terms of incidence of adverse reactions,there was no statistical difference between Huoxiang Zhengqi Pills combined with conventional treatment and conventional treatment alone. Other outcome measures were affected by various factors( such as inclusion of only 1 study or excessive heterogeneity among studies) and could not be concluded. Due to the limitations of the quality and quantity of included studies,this conclusion still needs to be verified by more high quality researches.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Gastroenteritis/drug therapy , Humans , Norfloxacin/therapeutic use , Randomized Controlled Trials as Topic , Treatment Outcome
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