Impact of Prophylactic Norfloxacin in Multidrug Resistant Bacterial Infections in the Early Liver Posttransplant Period.

OBJECTIVES: Norfloxacin is indicated as primary or secondary prophylaxis for spontaneous bacterial peritonitis in patients with cirrhosis. A history of spontaneous bacterial peritonitis favors colonization by multidrug-resistant bacteria. Infections caused by these bacteria increase morbidity and mortality after transplant. We investigated prophylactic norfloxacin as a risk factor for multidrug-resistant bacterial infections in the early posttransplant period. MATERIALS AND METHODS: This prospective cohort study included all adult liver recipients in 2 centers between 2015 and 2016. Recipients were classified into 2 groups according to whether or not they received prophylactic norfloxacin pretransplant. Data collection from liver recipients included pretransplant and first month after transplant clinical and microbiological data. Demographic and clinical data of corresponding donors were also collected. RESULTS: We included 157 liver recipients: 54 (34.6%) received norfloxacin and 103 (65.6%) did not received norfloxacin. There were 63 postoperative infections in 47 recipients (29.9%); 17/63 (27%) were multidrug- resistant bacterial infections. The urinary tract was the most commonly affected site (10/17 episodes, 58.8%), and Klebsiella pneumoniae was the microorganism most often isolated (8/17, 47.1%). Incidence of multidrug-resistant bacterial infection was higher in the norfloxacin group (22.2% vs 4.9%; relative risk = 5.6, 95% CI, 1.85-16.89; P = .001).This association was significant after controlling for most confounding factors, including pretransplant vasoactive support (P = .03), Model for End-Stage Liver Disease score (P = .01), previous spontaneous bacterial peritonitis (P = .02), chronic renal impairment (P = .005), number of packed red blood cells (P = .004), use of antilymphocyte globulin as induction (P = .006), and hepatocellular carcinoma (P = .02), but not pre- transplant antibiotic treatment (P = .06). CONCLUSIONS: For recipients who have received prophylactic norfloxacin, clinicians should be aware of the high risk of multidrug-resistant bacterial infections during the first month after liver transplant.

Norfloxacin-Induced Linear IgA Dermatosis.

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).

Norfloxacin Induced Recurrent Fixed Drug Eruption in a self Treated Adult Female Patient - A Case Report.

BACKGROUND: Fixed drug eruption is a clinical entity occurring at the same site each time the drug is administered. They are usually found on lips, genitalia, abdomen, and legs but can occur at any location. The eruptions usually occur within hours of administration of the drug and resolves spontaneously. Most common drugs causing them include antimicrobials. Fluroquinolones especially norfloxacin is commonly used in the treatment of gastrointestinal infections. Cutaneous adverse drug reactions are very rare with norfloxacin. CASE REPORT: In this case report, a young female, soon after taking Nofloxacin tablet, developed a blister with erythema and itching after self treatment for urinary tract infection. It got cured after stopping the drug and taking treatment from a dermatologist. It resolved as a hyper-pigmented scar. She experienced a similar episode of drug eruption on the same site when she again self medicated herself with Norfloxacin for diarrhoea. This time the reaction occurred within few hours and resolved with hyperpigmentation after medication. She was advised not to indulge in self-treatment in future. Suspecting association between the drug and the rash was confirmed and a diagnosis of Norfloxacin induced fixed drug eruption was made. CONCLUSION: Causality assessment by Naranjo's algorithm revealed a definite relationship between the cutaneous adverse drug reaction and the offending drug.

Safety and Efficacy of Rifaximin in Prophylaxis of Spontaneous Bacterial Peritonitis: A Systematic Review and Meta-analysis.

AIM: The role of rifaximin in the prevention of Spontaneous Bacterial Peritonitis (SBP) is not well studied. The aim of this meta-analysis was to evaluate the role of rifaximin in the prevention of SBP. METHODS: A computerized literature search for relevant clinical trials was conducted during August 2017. Data on Frequency of SBP, the success rate of prevention of SBP, mortality rate, hepatorenal syndrome, septic shock, hepatic encephalopathy, and GIT bleeding were extracted and pooled as Risk Ratio (RR) with their 95% Confidence Interval (CI) in a meta-analysis model. Heterogeneity was assessed by Chi-square test. RESULTS: Six studies involving 973 patients were included in the final analysis. The pooled effect estimate showed that the rifaximin plus norfloxacin group had less incidence of SBP (RR 0.58, 95% CI[0.37, 0.92], P=0.02) and hepatic encephalopathy (RR 0.38, 95% CI[0.17, 0.84], P=0.02) than the norfloxacin-based regimen group. No significant difference between rifaximin and norfloxacin in terms of frequency of SBP and success rate of primary prevention of SBP (RR 0.49, 95% CI [0.24, 1.01], P=0.05; RR1.21, 95% CI [0.95, 1.55], P=0.13, respectively). CONCLUSION: Based on our analysis, Rifaximin is a promising drug and appears to be a good alternative to norfloxacin in the prevention of SBP.

Performance of the nitrogen removal, bioactivity and microbial community responded to elevated norfloxacin antibiotic in an Anammox biofilm system.

Antibiotic pollution in nitrogen contained wastewater is an urgent issue. In this study, the nitrogen removal, biofilm property and microbial community of Anammox system were investigated with elevated norfloxacin (NOR) feeding. Batch experiments were carried out to detect the specific anammox activity (SAA) in each phase. Anammox system could resist NOR in 0.001-50 mg L-1, in which the nitrogen removal was firstly limited to 0.220 from the initial 0.345 by NOR suppression and then regained to 0.354 kg m-3 d-1 after acclimatization. SAA decreased to 7.56 from the initial 10.84 and then climbed up to 11.01 mg g-1 SS, while the relative abundance of Candidatus Kuenenia decreased to 11.33% and then picked up to 25.28% from the initial 20.74%. The suppression threshold on Anammox was calculated as 50-100 mg L-1 NOR, the NRR, SAA and Candidatus Kuenenia abundance all recovered to almost the initial level when NOR feeding was terminated.

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.

Resolution of norfloxacin-induced acute liver failure after N-acetylcysteine therapy: further support for the use of NAC in drug-induced ALF?

Liver injury due to idiosyncratic drug reactions can be difficult to diagnose and may lead to acute liver failure (ALF), which has a high mortality rate. N-acetylcysteine (NAC) is effective treatment for paracetamol toxicity, but its role in non-paracetamol drug-induced ALF is controversial. We report on the use of a validated bedside tool to establish causality for drug-induced liver injury (DILI) and describe the first case of resolution of norfloxacin-induced ALF after NAC therapy. NAC is easy to administer and generally has a good safety profile. We discuss the evidence to support the use of NAC in ALF secondary to DILI and possibilities for further clinical research in this field.

Efficacy and safety of alternating norfloxacin and rifaximin as primary prophylaxis for spontaneous bacterial peritonitis in cirrhotic ascites: a prospective randomized open-label comparative multicenter study.

BACKGROUND AND AIM: Primary prevention of spontaneous bacterial peritonitis (SBP) is an important strategy to reduce morbidity and mortality in cirrhotic patients with ascites. Efficacy and safety of alternating rifaximin and norfloxacin as primary prophylaxis is questionable. METHODS: Three hundred thirty-four cirrhotic patients with high SAAG (≥1.1) ascites, protein level in ascitic fluid less than 1.5 g/dL with advanced liver disease (Child-Pugh score >9 points with serum bilirubin level >3 mg/dL) or renal impairment (serum creatinine level >1.2 mg/dL, blood urea nitrogen level >25 mg/dL, or serum sodium level <130 mEq/L) were included in an open-label, randomized study aimed at comparing alternating use of norfloxacin and rifaximin vs. norfloxacin or rifaximin alone as primary prophylaxis for SBP. Both intention-to-treat and per-protocol efficacy analyses were done after 6 months of treatment by assessment of ascitic fluid neutrophil count. Safety analysis was done for all intention-to-treat populations. RESULTS: Alternating norfloxacin and rifaximin showed superior prophylaxis by intention-to-treat (74.7 vs. 56.4% vs. 68.3%, p < 0.048). Pairwise analysis showed that alternating regimen had lower probability to develop SBP when compared to a norfloxacin-based regimen in intention-to-treat (p = 0.016) and per protocol analysis (p = 0.039). There was no difference among the studied groups regarding the incidence and severity of adverse events reported. CONCLUSIONS: Alternating norfloxacin- and rifaximin-based primary prophylaxis for SBP showed higher efficacy with the same safety profile when compared with monotherapy of norfloxacin.

Norfloxacin--toxicity for Zebrafish (Danio rerio) focused on oxidative stress parameters.

The aim of the study was to investigate the effects of subchronic exposure of zebrafish (Danio rerio) to a fluoroquinolone norfloxacin, using selected oxidative stress parameters as a target. Toxicity tests were performed on zebrafish according to the OECD Guidelines number 203 and number 215. In the Subchronic Toxicity Test, a significant (P < 0.01) increase in the activity of glutathione peroxidase, glutathione S-transferase, and catalase was found. In the test, norfloxacin did not affect lipid peroxidation and catalytic activity of glutathione reductase. From the results, we can conclude that norfloxacin has a negative impact on specific biochemical processes connected with the production of reactive oxygen species in fish tested.

[Comparative effectiveness of fluoroquinolones and beta-lactams in the complex therapy of patients with chronic pyelonephritis].

A comparative study has evaluated the effect of fluoroquinolones and beta-lactams on clinical and biochemical manifestations of chronic pyelonephritis (CPN). 108 patients aged from 18 to 59 years (mean age - 40.26 +/- 10.09 years) with secondary CPN against dysmetabolic nephropathy and nephrolithiasis in a phase of active inflammation were observed. The majority of patients were women - 89 (82.4%). CPN was diagnosed in accordance with the N.A. Lopatkin and V.E. Rodoman clinical classification (1974) based on results of complete clinical and laboratory, radiologic and ultrasound examinations. Special methods of investigation included determination of the activity of lipid peroxidation, antioxidant system and the structural parameters of the cell membrane ofpolymorphonuclear leukocytes (PMN). Pain, dysuria, and intoxication syndrome were arrested in all patients after 14 days of therapy. The high efficacy was reported for patients treated with sparfloxacin. A similar trend was observed in the dynamics of intoxication syndrome regression. In addition, there was a significant reduction of lipid peroxidation products and an increase of alpha-tocopherol in the PMN membranes; the content of phospholipids significantly increased and cholesterol level declined during the treatment. The results showed that use of fluoroquinolones and the B-lactams in the treatment of patients with CPN against the nephrolithiasis leads to a significant relief of clinical symptoms of the disease, as well as to restoration the structural and functional state of PMN membranes. The most distinct and early clinical-laboratory effect was obtained against the background of use of fluoroquinolone sparfloxacin.

Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study.

OBJECTIVES: To characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone. DESIGN: Population based nested case-control study. SETTING: Ontario, Canada, from 1 April 1992 to 1 March 2010. PARTICIPANTS: Cases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case's index date. MAIN OUTCOME MEASURES: Odds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia. RESULTS: During the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17,859/165,754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was found with norfloxacin (adjusted odds ratio 1.6, 0.8 to 3.4) CONCLUSIONS: Among older patients receiving spironolactone, treatment with trimethoprim-sulfamethoxazole was associated with a major increase in the risk of admission to hospital for hyperkalaemia. This drug combination should be avoided when possible.

Tamoxifen/norfloxacin interaction leading to QT interval prolongation in a female patient with extracranial meningioma.

The authors report on a case of tamoxifen/norfloxacin interaction leading to QT interval prolongation in an 83-year-old female patient with extracranial meningioma treated with radiation and hormonal therapy (with Tamoxifen). This case report highlights the potential risk of tamoxifen causing depression of electrical impulse in sinoatrial node, leading to symptomatic sinus bradycardia with prolonged QT interval. At the same time it indicates the need to be on the look out for drug interactions (in our case between tamoxifen and norfloxacin), as well as to be aware of other drugs possibly inducing QT interval prolongation (Fig. 2, Ref. 7).

Quantitative comparison of the convulsive activity of combinations of twelve fluoroquinolones with five nonsteroidal antiinflammatory agents.

Concomitant administration of certain fluoroquinolone antimicrobials and nonsteroidal antiinflammatory agents (NSAIDs) induces serious convulsion in humans. There are differences in convulsive activity among fluoroquinolones and in the potentiation of fluoroquinolone-induced convulsion among NSAIDs, but a comprehensive, quantitative comparison has not been carried out. This study evaluates the inhibitory effects of twelve fluoroquinolones (ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, norfloxacin, ofloxacin, pazufloxacin, prulifloxacin, sparfloxacin, and tosufloxacin) alone or in the presence of an NSAID (4-biphenylacetic acid, diclofenac sodium, loxoprofen, lornoxicam or zaltoprofen) on the GABA(A) receptor binding of [(3)H]muscimol in an in vitro study using mice synaptic plasma membrane. The rank order of inhibitory effects of the fluoroquinolones was prulifloxacin asymptotically equal to norfloxacin > ciprofloxacin > or = enoxacin > gatifloxacin > or = ofloxacin asymptotically equal to tosufloxacin asymptotically equal to lomefloxacin > levofloxacin > or = sparfloxacin > or = pazufloxacin asymptotically equal to fleroxacin. 4-Biphenylacetic acid most potently enhanced the inhibitory effects of the fluoroquinolones, while zaltoprofen, loxoprofen, lornoxicam and diclofenac had essentially no effect. The clinical risk of convulsion for each combination was estimated using a pharmacodynamic model based on receptor occupancy using the in vitro data set obtained and pharmacokinetic parameters in humans collected from the literature. The combinations of 4-biphenylacetic acid with prulifloxacin and enoxacin were concluded to be the most hazardous.