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).

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.

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).

[A comparison of efficacy and tolerance of furamag and norbactin in the treatment of acute cystitis in females].

Efficacy and tolerance of furamag and norbactin were compared in a prospective controlled trial with participation of 82 females aged 18-60 years with acute uncomplicated cystitis. All the women were divided into two groups. Group 1 (n=42) received norbactin (norfloxacin) in a dose 400 mg twice a day for 7 days. Group 2 (n=40) was given furamag in a dose 50 mg 3 times a day for 10 days. The results were evaluated 2 weeks after the treatment. The comparison of the treatment results showed that a new nitrofuranic drug furamag has significantly higher clinical and bacteriological efficacy: acute cystitis was cured in 95% patients, eradication of the infective agent occurred in 96.4% patients, tolerance was good in 97.5% patients. Sensitivity of the agents causing acute cystitis to nitrofurans reached 98.2% while to norbactin--only 86%.

Generating signals of drug-adverse effects from prescription databases and application to the risk of arrhythmia associated with antibacterials.

BACKGROUND: Although it is well known that a variety of antibacterials may incidentally cause malignant arrhythmia, the list of drugs causing arrhythmia and the impact of these adverse effects are still uncertain. We investigated on this topic by using a large prescription database with different observational designs. METHODS: Prescription data on all incident users of several antibacterial and antiarrhythmic drugs over the period July 1997 through December 1999 were retrieved from the Drug Prescription Database (DPD) of the Italian Province of Varese. The association between the use of antibacterial and antiarrhythmic drugs was investigated by applying prescription sequence symmetry, cohort and nested case-control designs. RESULTS: Lower proarrhythmic effects were on an average obtained from prescription sequence symmetry approach with respect to both cohort and nested case-control. Evidence of association between exposure to drugs (erythromycin and ciprofloxacin) and the risk of arrhythmia was consistently found by the three approaches. No other signals were generated from the prescription sequence symmetry analysis. Two drugs (clarithromycin and levofloxacin) showed patterns compatible with an arrhythmic effect according to both cohort and nested case-control designs. CONCLUSIONS: Prescription databases are useful tools to explore drug safety through both conventional and emerging observational designs. In spite of its appealing features, prescription sequence symmetry design shows lower sensitivity with respect to conventional designs. Evidence about the association between the use of certain macrolides and fluoroquinolones and the onset of arrhythmia is confirmed by this study.

Clinical toxicological aspects of fluoroquinolones.

Reactions of the gastrointestinal tract and the central nervous system are the most often observed adverse effects during therapy with fluoroquinolones. Pathogenesis of the neurotoxic effects of fluoroquinolones could be related to the activation of the NMDA receptor. Animal experiments as well as clinical experience show that the cardiotoxic potentials of sparfloxacin and grepafloxacin are higher than those of the other fluoroquinolones: they cause QT prolongation at rather low doses thus increasing the risk for severe arrhythmia (torsades de pointes). Phototoxicity has been described for all quinolones, but derivatives with a halogen atom at position 8 show the highest potential for such reactions (e.g. clinafloxacin). Chondrotoxicity of quinolones can affect the articular cartilage and the epiphyseal growth plate in immature animals; the use of these drugs in pediatrics should be restricted to carefully selected indications (such as the use of ciprofloxacin in cystic fibrosis). Tendinitis and tendon ruptures can also be induced by quinolones. Overall, quinolones are as well tolerated as most other anti-microbial agents. However, their specific toxic potentials have to be considered when they are chosen for treatment of bacterial infections.

Malignant hyperthermia susceptibility revealed by myalgia and rhabdomyolysis during fluoroquinolone treatment.

Fluoroquinolones cause myalgia, but this complication is not clearly documented. We describe a patient who developed myalgia and rhabdomyolysis during fluoroquinolone treatment. The patient was a 33-year-old man treated with norfloxacin for common cystitis. He complained of general muscular fatigue, tendon disorders, and articular pain during treatment. When the antimicrobial agent was stopped, symptoms decreased, with persistence of slight myalgia for 10 days. Rhabdomyolysis was detected. Six months later, investigation by 31P magnetic resonance spectroscopy revealed an oxidative disorder and an abnormal abundance of phosphomonoesters. In vitro contracture tests led to a diagnosis of malignant hyperthermia susceptibility. Our case shows that for any subject presenting myalgia with rhabdomyolysis triggered by fluoroquinolone treatment, the presence of a latent myopathy should be investigated.

[Fever in intensive care: keep medications in mind at all times]. / Koorts op de intensive care: denk ook altijd aan geneesmiddelen.

In two patients, men aged 35 and 69 years admitted postoperatively to the intensive care unit, fever of unknown origin developed. One had been admitted because aspiration was suspected. He had been treated immediately with amoxicillin and clavulanic acid. The other had undergone oesophageal excision and gastric reconstruction because of oesophageal carcinoma and had been subjected to antibiotic decontamination (amphotericin B, norfloxacine en fungizone). No cause for the fever was detected, but it quickly subsided after discontinuation of the amoxicillin-clavulanic acid and the norfloxacine, respectively. When encountering fever of unknown origin in intensive care patients it is always important to think of drug fever.

Allergic nephropathy associated with norfloxacin and ciprofloxacin therapy. Report of two cases and review of the literature.

Allergic nephropathy associated with quinolone antibiotics has been reported in an increasing number of cases. The mechanism might be a hypersensitivity reaction. Norfloxacin has been incriminated previously as a cause once only, with acute interstitial nephritis (AIN) as the histopathological finding. Ciprofloxacin-associated nephropathy has been reported in 28 cases, with AIN as the main histopathological finding. This report describes a second case of AIN associated with norfloxacin treatment and another ciprofloxacin-associated renal interstitial drug adverse reaction. Clinicians should be aware of quinolone-associated AIN, which is a rare but potentially dangerous renal complication.

[Immune thrombocytopenia attributed to norfloxacin]. / Immuuntrombocytopenie toegeschreven aan norfloxacine.

A 65-year-old woman developed haemorrhagic diathesis due to a profound thrombocytopenia (thrombocyte count: 1 x 10(9)/l) within one week after a 10-day course of norfloxacin (2 x 400 mg/day), prescribed for cystitis. On account of increased megakaryopoiesis in the bone marrow and absence of other causes of thrombocytopenia norfloxacin-induced immune thrombocytopenia was diagnosed. No norfloxacin-dependent antibodies against platelets were detected. Treatment with prednisone (1.5 mg/kg/day) resulted in the normalization of the platelet count within 5 days.

[Repeated rupture of the extensor tendons of the hand due to fluoroquinolones. Apropos of a case]. / Rupture itérative des tendons extenseurs de la main sous fluoroquinolones. A propos d'un cas.

Fluoroquinolone toxicity on cartilages and tendons has been well known since 1983. Tendon inflammation or rupture has been described. Achilles tendon rupture is the most frequent complication but many other sites of tendon injuries have been reported. This article presents a case of rupture of extensor tendons of the hand in an elderly woman treated by fluoroquinolones. As far as we know, this site of tendon lesion has never been previously described. Histological examination of tendon injuries was possible after surgical treatment. Histological structures were similar to the classical description but had specific features. Like other authors, we think that the mechanism of the disease involves vascular disorders as well as direct toxicity. The histological lesions seem to be different in chronic and acute forms.