Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections.

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.

Norfloxacin versus alternative antibiotics for prophylaxis of spontaneous bacteria peritonitis in cirrhosis: a systematic review and meta-analysis.

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.

Primary Norfloxacin Prophylaxis for APASL-Defined Acute-on-Chronic Liver Failure: A Placebo-Controlled Double-Blind Randomized Trial.

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.

Paeoniflorin combined with norfloxacin ameliorates drug-resistant Streptococcus suis infection.

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.

Effect of Carvacrol and Thymol on NorA efflux pump inhibition in multidrug-resistant (MDR) Staphylococcus aureus strains.

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.

The Risk of Clostridioides difficile Infection in Cirrhotic Patients Receiving Norfloxacin for Secondary Prophylaxis of Spontaneous Bacterial Peritonitis-A Real Life Cohort.

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.

Improved Stability and Activity of a Marine Peptide-N6NH2 against Edwardsiella tarda and Its Preliminary Application in Fish.

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.

Comparative efficacy of long-term antibiotic treatments in the primary prophylaxis of spontaneous bacterial peritonitis.

BACKGROUND & AIMS: Several antibiotic treatments aiming to prevent spontaneous bacterial peritonitis (SBP) in cirrhotic patients with low-protein content in ascitic fluid have been tested; however, there are limited data on the comparative efficacy of these regimens. We assessed their comparative efficacy through a network meta-analysis and using GRADE criteria to appraise quality of evidence. METHODS: Through literature review through October 2018, we identified 10 randomized controlled trials comparing antibiotic treatments (norfloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole and rifaximin) with each other or placebo. Primary outcome was SBP occurrence, with mortality rate and rate of other infections as secondary outcomes. RESULTS: In comparison with placebo, moderate quality evidence supports the use of norfloxacin and ciprofloxacin in primary prophylaxis of SBP (risk ratio 0.23; 95% CI, 0.09-0.56; P = 0.001 and 0.23; 0.07-0.79; P = 0.02 respectively) while only low quality evidence suggests superiority of rifaximin (risk ratio 0.15; 0.05-0.42). When antimicrobial agents were compared to each other, no significant difference was found. With regard to mortality, moderate quality supports the superiority of norfloxacin over placebo (risk ratio, 0.68; 95% CI, 0.47-0.99; P = 0.04), while ciprofloxacin and rifaximin showed only a non-significant benefit and no significant difference was found in the other comparisons. None of the tested antibiotics proved to significantly decrease the rate of other infections. CONCLUSIONS: Norfloxacin appears to have significant benefit both in terms of SBP prevention and mortality; ciprofloxacin represents a valuable option although without a clear survival benefit. Rifaximin shows interesting results but needs to be tested in further trials.

Gut derived-endotoxin contributes to inflammation in severe ischemic acute kidney injury.

BACKGROUND: Recent researches indicate that the intestinal consequences of renal ischemia reperfusion (IR) would predispose to the translocation of gut-derived endotoxin. Here, we designed experiments to test the hypothesis that the gut-derived endotoxin has a potential role in mediating local inflammatory processes in the acutely injured kidney. METHODS: Rats were performed sham or renal IR surgery (60 min of bilateral renal ischemia, then 24 h of reperfusion) (n = 5). The intestinal structural and mucosa permeability were evaluated. Serum endotoxin and bacterial load in liver and mesenteric lymph nodes (MLN) were measured. Separate groups were pretreated with oral norfloxacin 20 mg/kg/day or saline for 4 weeks and divided into sham plus saline, sham plus norfloxacin, renal IR plus saline and renal IR plus norfloxacin group. Serum biochemistry and endotoxin were determined. Kidney pathological changes were scored. Protein or mRNA expression of toll-like receptor 4 (TLR4) and proinflammatory mediators were measured in kidney homogenate. RESULTS: Renal IR led to marked intestinal integrity disruption and increase in intestinal permeability. These are accompanied by low grade of endotoxemia as well as increased bacterial load in liver and MLN. The group pretreated with norfloxacin showed significant attenuation of the increase in serum urea, ALAT, ASAT and endotoxin. The increased renal protein or mRNA of TLR4 and proinflammatory mediators (IL-6 and MCP-1) in the unpretreated animals was significantly attenuated in the norfloxacin-pretreated animals. However, norfloxacin pretreatment did not produce any protective effects on renal tubular integrity. CONCLUSIONS: Our results show for the first time that gut-derived endotoxin, resulting from an increased intestinal permeability after severe renal IR, subsequently amplifies intrarenal inflammatory response by activation renal TLR4 signaling. Our study results do not establish that antibiotic administration was effective in improving the overall renal outcome. However, our findings may be the first step to understanding how to tailor therapies to mitigate intrarenal inflammation in select groups of patients.

[Systematic review and Meta-analysis of Huoxiang Zhengqi Pills combined with Western medicine for acute gastroenteritis].

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.

Daily Norfloxacin vs. Weekly Ciprofloxacin to Prevent Spontaneous Bacterial Peritonitis: A Randomized Controlled Trial.

OBJECTIVES: For the prevention of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites, norfloxacin 400 mg per day is recommended as a standard regimen. This study aims to investigate whether ciprofloxacin once weekly administration is not inferior to norfloxacin once daily administration for the prevention of SBP. METHODS: This is an investigator-initiated open-label randomized controlled trial conducted at seven tertiary hospitals in South Korea. Liver cirrhosis patients with ascites were screened, and enrolled in this randomized controlled trial if ascitic protein ≤1.5 g/dL or the presence of history of SBP. Ascitic polymorphonucleated cell count needed to be <250/mm3. Patients were randomly assigned into norfloxacin daily or ciprofloxacin weekly group, and followed-up for 12 months. Primary endpoint was the prevention of SBP. RESULTS: One hundred twenty-four patients met enrollment criteria and were assigned into each group by 1:1 ratio (62:62). Seven patients in the norfloxacin group and five patients in the ciprofloxacin group were lost to follow-up. SBP developed in four patients (4/55) and in three patients (3/57) in each group, respectively (7.3% vs. 5.3%, P = 0.712). The transplant-free survival rates at 1 year were comparable between the groups (72.7% vs. 73.7%, P = 0.970). Incidence of infectious complication, hepatorenal syndrome, hepatic encephalopathy, and variceal bleeding rates were not significantly different (all P = ns). The factors related to survival were models representing underlying liver function. CONCLUSION: Once weekly ciprofloxacin was as effective as daily norfloxacin for the prevention of SBP in cirrhotic patients with ascites.

Low-dose Norfloxacin-treated leptospires induce less IL-1ß release in J774A.1 cells following discrepant leptospiral gene expression.

Currently, accumulating evidence is challenging subtherapeutic therapy. Low-dose Norfloxacin (Nor) has been reported to suppress the immune response and worsen leptospirosis. In this study, we investigated the influence of low-dose Nor (0.03 µg/ml, 0.06 µg/ml, 0.125 µg/ml) on leptospiral gene expression and analyzed the immunomodulatory effects of low-dose Nor-treated leptospires in J774A.1 cells. To study the expression profiles of low-dose Nor-treated leptospires, we chose LipL71/LipL21 as reference genes determined by the geNorm applet in this experiment. The results showed that low-dose Nor up-regulated the expression of FlaB and inhibited the expression of 16S rRNA, LipL32, LipL41, Loa22, KdpA, and KdpB compared with the untreated leptospires. These results indicated that low-dose Nor could regulate leptospiral gene expression. Using RT-PCR, the gene expression of IL-1ß and TNF-α in J774A.1 cells was detected. Nor-treated leptospires induced higher expression levels of both IL-1ß and TNF-α. However, when analyzed by ELISA, the release of mature IL-1ß was reduced compared with that observed in cells induced with no Nor-treated leptospires, although the TNF-α protein level showed no significant change. Our study indicated that the gene expression of leptospires could be modulated by low-dose Nor, which induced less IL-1ß release in J774A.1 cells.

A systematic review of randomised clinical trials for oral antibiotic treatment of acute pyelonephritis.

There is increasing resistance to the oral antibiotics currently recommended for the treatment of pyelonephritis, and increased healthcare costs are associated with the reliance on alternative intravenous agents. We, therefore, performed a systematic review of randomised controlled trials to determine the clinical efficacy and safety of oral antibiotics for the treatment of pyelonephritis in adults. A search of four major medical databases (MEDLINE, Embase+ Embase classic, CENTRAL and Cochrane Database for Systematic Reviews) in addition to manual reference searching of relevant reviews was conducted. Clinical cure and adverse event rates were reported, and trial quality and bias were assessed. A total of 277 studies were reviewed; five studies matched all eligibility criteria and were included. Antibiotics included were cefaclor, ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, loracarbef, norfloxacin, rufloxacin and trimethoprim-sulfamethoxazole. In included studies, the clinical success of the outpatient treatment of pyelonephritis by cefaclor, ciprofloxacin and norfloxacin at 4 to 6 weeks was comparable at between 83 to 95%. Relatively high rates of adverse events were noted in a trial of ciprofloxacin (24%) and trimethoprim-sulfamethoxazole (33%). Significant heterogeneity between all aspects of the trial designs was identified, with all studies having a potential for bias. This review demonstrates a need for high-quality clinical trials into the oral antibiotic treatment of pyelonephritis, with more consistent designs and reporting of outcomes. There are data to support further research into oral norfloxacin and cefaclor for the outpatient treatment of pyelonephritis in adults.

Central Nervous System Symptoms Due to Transient Methemoglobinemia in a Child With G6PD Deficiency.

The authors herein report a 5-year-old child who presented with massive hemolysis, irritability, and cyanosis. The final diagnosis was glucose-6-phosphate dehydrogenase deficiency with associated central nervous system symptoms probably because of concomitantly acquired methemoglobinemia following oxidant drug exposure. The associated acute-onset anemia would have contributed to the development of cerebral anoxia-related seizures and encephalopathy.

Selective intestinal decontamination with norfloxacin enhances a regulatory T cell-mediated inflammatory control mechanism in cirrhosis.

BACKGROUND & AIMS: Norfloxacin exerts immunomodulatory effects in cirrhosis beyond its bactericidal activity. We aimed at identifying the role of regulatory T (Treg) cells in the norfloxacin mechanism that compensates the inflammatory environment in cirrhosis. PATIENTS & METHODS: Consecutively admitted patients with cirrhosis and ascitic fluid (AF) with: spontaneous bacterial peritonitis (SBP), non-infected AF, and norfloxacin as secondary SBP prophylaxis (SID group). Tregs were defined by flow-cytometry as CD4+ CD25+ FoxP3+ cells. Dendritic cells (DCs) were purified for co-stimulatory signalling evaluation and norfloxacin and IL-10 levels were measured in serum. Wildtype and recombination activating gene 1 (Rag1)-deficient mice with CCl4 -induced cirrhosis were used for adoptive-transfer experiments using naïve CD4+ T cells and Tregs. RESULTS: Eighty-four patients were included. Treg percentage was significantly increased in SID patients compared with SBP or non-infected AF patients. A positive correlation was observed between Tregs and serum norfloxacin and IL-10 levels. DCs from SID patients showed a significantly decreased expression of CD80 and CD86 compared with SBP and non-infected AF patients and correlated with norfloxacin levels. Modulation of co-stimulatory signalling by norfloxacin was not detected in Rag1-deficient mice and Rag1-deficient mice reconstituted with naïve T-cells. However, reconstitution with naïve T-cells and Tregs was associated with significantly downregulated CD80 and CD86 expression in the presence of norfloxacin. Norfloxacin immunomodulatory effect on IL-2 and IFN-gamma reduction and on the increase of IL-10 was significantly achieved only when the Tregs were restored in Rag1-deficient mice. CONCLUSIONS: These results provide a plausible mechanism for the immunomodulatory effects of norfloxacin in cirrhosis beyond its bactericidal effect.

Nitrofurantoin vs other prophylactic agents in reducing recurrent urinary tract infections in adult women: a systematic review and meta-analysis.

BACKGROUND: The clinical and financial burden from bladder infections is significant. Daily antibiotic use is the recommended strategy for recurrent urinary tract infection prevention. Increasing antibiotic resistance rates, however, require immediate identification of innovative alternative prophylactic therapies. This systematic review aims to provide guidance on gaps in evidence to guide future research. OBJECTIVE: The objective of this review was to provide current pooled estimates of randomized control trials comparing the effects of nitrofurantoin vs other agents in reducing recurrent urinary tract infections in adult, nonpregnant women and assess relative adverse side effects. DATA SOURCES: Data sources included the following: MEDLINE, Jan. 1, 1946, to Jan. 31, 2015; Cochrane Central Register of Controlled Trials the Cochrane Database of Systematic Reviews, and web sites of the National Institute for Clinical Excellence, and the National Guideline Clearinghouse from 2000 to 2015. Randomized control trials of women with recurrent urinary tract infections comparing nitrofurantoin with any other treatment were included. STUDY DESIGN: A protocol for the study was developed a priori. Published guidance was followed for assessment of study quality. All meta-analyses were performed using random-effects models with Stats Direct Software. Dual review was used for all decisions and data abstraction. RESULTS: Twelve randomized control trials involving 1063 patients were included. One study that had a serious flaw was rated poor in quality, one study rated good, and the remainder fair. No significant differences in prophylactic antibiotic treatment with nitrofurantoin and norfloxacin, trimethoprim, sulfamethoxazole/trimethoprim, methamine hippurate, estriol, or cefaclor were found in clinical or microbiological cure in adult nonpregnant women with recurrent urinary tract infections (9 randomized control trials, 673 patients, relative risk ratio, 1.06; 95% confidence interval, 0.89-1.27; I2, 65%; and 12 randomized control trials, 1063 patients, relative risk ratio, 1.06; 95% confidence interval, 0.90-1.26; I2, 76%, respectively). Duration of prophylaxis also did not have a significant impact on outcomes. There was a statistically significant difference in overall adverse effects, with nitrofurantoin resulting in greater risk than other prophylactic treatments (10 randomized control trials, 948 patients, relative risk ratio, 2.17; 95% confidence interval, 1.34-3.50; I2, 61%). Overall, the majority of nitrofurantoin adverse effects were gastrointestinal, with a significant difference for withdrawals (12 randomized control trials, 1063 patients, relative risk ratio, 2.14; 95% confidence interval, 1.28-3.56; I2, 8%). CONCLUSION: Nitrofurantoin had similar efficacy but a greater risk of adverse events than other prophylactic treatments. Balancing the risks of adverse events, particularly gastrointestinal symptoms, with potential benefits of decreasing collateral ecological damage should be considered if selecting nitrofurantoin.

Effect of norfloxacin therapy for acute, uncomplicated lower urinary tract infection on vaginal Candida prevalence.

INTRODUCTION AND HYPOTHESIS: Acute uncomplicated lower urinary tract infections (UTI) and vulvovaginal candidiasis (VVC) both occur frequently in women. Although VVC is believed to commonly occur after antibiotic therapy, few studies have demonstrated this association. Thus, the aim of the study was to estimate the prevalence of colonization by Candida spp. and VVC after norfloxacin (NOR) use for UTI and the effects on the vaginal microbiota and inflammatory process. METHODS: This was a prospective cohort study of women with culture-proven UTI who were treated with NOR (antibiotic group). The control group consisted of women with noninfectious diseases or in preventive care. Candida vaginal infections were monitored both clinically and mycologically at baseline and at the follow-up evaluation. RESULTS: All women showed UTI remission after NOR treatment, and no woman in either group, antibiotic and control, showed symptoms of VVC. Both groups showed similar ratios of a positive Candida culture at baseline (6.7 % and 12.8 %, respectively) and at follow-up (3.3 % and 8.5 %, respectively) (p = 0.2768 and p = 0.5035, respectively). The antibiotic group showed no increased risk of Candida colonization or VVC after NOR treatment compared with the control group [odds ratio (OR) 0.556, 95 % confidence interval (CI) 0.2407-10.05]. CONCLUSIONS: NOR was effective for UTI treatment, did not increase the risk of vaginal colonization by Candida or VVC, and did not lead to major disturbances of the vaginal microbiota.

Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women.

BACKGROUND: The antibiotic nitrofurantoin is commonly used to treat uncomplicated urinary tract infections. However, when this drug is used by patients with reduced kidney function, its urine concentration may be subtherapeutic. METHODS: We conducted a population-based study of older women (mean age 79 years) in Ontario, Canada, whose estimated glomerular filtration rate was relatively low (median 38 mL/min per 1.73 m(2)) and for whom 1 of 4 antibiotics had been prescribed for urinary tract infection: nitrofurantoin, ciprofloxacin, norfloxacin or trimethoprim-sulfamethoxazole. We assessed 2 measures of treatment failure in the subsequent 14 days: receipt of a second antibiotic indicated for urinary tract infection and hospital encounter (emergency department visit or hospital admission) with a urinary tract infection. We repeated the analysis for older women with relatively high estimated glomerular filtration rate (median 69 mL/min per 1.73 m(2)). RESULTS: The baseline characteristics of the 4 antibiotic groups were similar. Relative to nitrofurantoin, the other antibiotics (including ciprofloxacin) were associated with a lower rate of treatment failure among women with relatively low estimated glomerular filtration rate (for ciprofloxacin v. nitrofurantoin: second antibiotic prescription, 130/1989 [6.5%] v. 516/3739 [13.8%], odds ratio [OR] 0.44, 95% confidence interval [CI] 0.36-0.53; hospital encounter, 21/1989 [1.1%] v. 95/3739 [2.5%], OR 0.41, 95% CI 0.25-0.66). However, a similar risk of treatment failure with nitrofurantoin was also observed among women with relatively high estimated glomerular filtration rate. The results were consistent in multiple additional analyses. INTERPRETATION: In this study, the presence of mild or moderate reductions in estimated glomerular filtration rate did not justify avoidance of nitrofurantoin.

Treatment of Spontaneous Bacterial Peritonitis.

Spontaneous bacterial peritonitis (SBP) is an infection of patients with cirrhosis and ascites. This peculiarity is due to the frequent intestinal translocation that allows bacteria to cross the intestinal barrier, colonizing the ascitic fluid. In cirrhosis, SBP is inferior only to urinary tract infections. It is prevalently sustained by Gram-negative bacteria such as Escherichia coli and Klebsiella. Risk factors for developing SBP are advanced age, refractory ascites, variceal bleeding, renal failure, low albumin levels (below 2.5 g/ml), bilirubin over 4 mg/dl, Child-Pugh class C and a previous diagnosis of SBP. Thus, this is an indication for a long-term antibiotic prophylaxis with norfloxacin. Renal failure - especially the hepatorenal syndrome - complicates SBP in about 20% of cases independently of the efficacy of the antibiotic therapy. The mortality of these patients is about 90%. Infusion of albumin significantly reduces the incidence of hepatorenal syndrome and consequently the risk of death. Long-term quinolonic prophylaxis as well as increased antibiotic therapies are causing the emergence of multidrug-resistant agents as frequent causes of SBP. In such cases, the antibiotic sensitivity to quinolones is low, and European recommendations suggest a second-line antibiotic therapy, including meropenem or piperacillin plus tazobactam. Collection of blood, urine and ascitic fluid for cultures is important for bacterial recognition, possibly before starting an empirical antibiotic therapy. Indeed, the probability of positive cultures rapidly vanishes when they are performed during already implemented antibiotic administration. It is important to know that a failure of the first-line therapy is associated with an increased probability of death.