Pefloxacin induced changes in serotonergic innervation and mast cell number in rat salivary glands.

Pefloxacin is a second-generation fluoroquinolone antibiotic. Besides its advantageous characteristics, side effects including the hypofunction of salivary glands, decreased saliva production, and peripheral neuropathy were observed during the administration of pefloxacin. The aim of this study was to investigate the changes in the number of serotonergic immunoreactive fibers and mast cells after pefloxacin treatment in the parotid and sublingual glands of rats to detect the possible neurotoxic effect of pefloxacin. The adult female rats were treated with intraperitoneal (i.p.) injection of pefloxacin for three or seven days (at a concentration of 20 mg/100g body weight) and the serotonergic innervation pattern along with the change in mast cell number were evaluated by using histochemistry and immunohistochemistry in the parotid and sublingual glands. We found that a three-day treatment significantly increased the number of immunoreactive serotonergic nerve fibers, but after a seven-day treatment the number of serotonin positive nerve fibers decreased almost to values of the control group. The alteration of mast cell number was parallel with the changes of the serotonin positive fibers during the treatment. These results suggest that pefloxacin treatment can modify the finely controlled communication between the immune- and the peripheral nervous systems, resulting neurogenic inflammatory process. The background of this process is the altered serotonergic innervation and the increased number of activated mast cells releasing different mediators for example histamine, which can finally lead to reduced number of serotonin positive nerve fibers after a seven-day treatment of pefloxacin leading to atrophy and hypofunction of the salivary glands.

Effect of azithromycin and pefloxacin in treatment of acute enteritis based on clinical efficacy comparison.

This paper aims to compare and analyze clinical efficacy of azithromycin and pefloxacin in treatment of acute enteritis. The 160 patients with acute enteritis were randomly divided into a study group (n=80) treated with azithromycin, and a reference group (n=80) treated with pefloxacin. We compared overall treatment efficiency (markedly, effective, invalid), clinical symptoms and signs remission time (antipyretic time, antidiarrheal time, symptoms and signs disappearance time), interleukin-6 and C-reactive protein concentration before and after treatment, adverse reactions rate (nausea, abdominal pain, headache, etc.). In comparison of overall treatment efficiency of the two groups, the results showed that the study group was significantly superior to the reference group (P<0.05). In comparison of clinical symptoms and signs remission time of the two groups, the study group were significantly shorter than the reference group (P<0.05). At the same time, in comparison of levels of interleukin-6 and C-reactive protein concentration after treatment, the study group was significantly superior to the reference group (P<0.05). There was no significant difference between the two groups in incidence of adverse reactions (P<0.05). The efficacy of azithromycin for acute enteritis is better than that of pefloxacin, and it can significantly reduce clinical symptom remission time. Moreover, safe and reliable, it has great value in clinical application.

Effects of pefloxacin in multi drug resistant typhoid Fever.

In 28 children, with bacteriologically and/or serologically diagnosed typhoid fever treated at CMH, Rawalpindi in 2003, first one of the three recommended drugs (viz. chloramphenicol, amoxycillin or co-trimoxazole) was given for 7 days for defervescence to occur. In those who failed to respond a second trial of therapy with one of the other two drugs was initiated, after excluding the first drug. A second failure of therapy was taken as an indication to use pefloxacin singly. Finally, 18 (64.3%) cases responded to chloramphenicol or amoxycillin or co-trimoxazole. Pefloxacin was used in 10 (35.7%) cases. The failure rate of treatment with chloramphenicol was 50%, with amoxycillin 71.4% with co-trimoxazole 75% and 0% with pefloxacin. An analysis of the 28 cases revealed that apart from fever (in 100%), splenomegaly (in 82.1%) was the most important clinical indicator to diagnosis. along with absolute eosinopenia (in 71.4%). There were no major complications, except 2 cases with typhoid hepatitis that responded to choramphenicol and co-trimoxazole, respectively. Blood culture grew Salmonella typhi in 7 cases of which 5 (72%) were multi drug resistant S. typhi.

Fluoroquinolones in children: poorly defined risk of joint damage.

(1) Rare but well-documented cases of joint damage, with no other identified cause, have been reported in children treated with systemic fluoroquinolones. The joint damage usually resolves gradually after drug withdrawal and are more frequent with pefloxacin. (2) The few available paediatric trials included too few patients to identify rare adverse effects on joints, or to show a causal relationship between treatment and joint damage. (3) In practice, quinolones are an option for children only when the expected benefit outweighs the risk of joint damage. In the rare cases in which fluoroquinolone therapy is justified, ciprofloxacin is the drug of first choice. Pefloxacin should be avoided.

Fluoroquinolone-associated tendinopathy: a critical review of the literature.

With the expanded use of fluoroquinolones for the treatment of community-acquired respiratory infections and reports of tendon injury linked to the use of these agents, we reviewed the literature to investigate the frequency and strength of this association. Ninety-eight case reports were available for review. The incidence of tendon injury associated with fluoroquinolone use is low in a healthy population but increases in patients who have renal dysfunction, who are undergoing hemodialysis, or who have received renal transplants. Pefloxacin and ciprofloxacin were most frequently implicated, but tendon injury was reported with most fluoroquinolones. The median duration of fluoroquinolone treatment before the onset of tendon injury was 8 days, although symptoms occurred as early as 2 hours after the first dose and as late as 6 months after treatment was stopped. Up to one-half of patients experienced tendon rupture, and almost one-third received long-term corticosteroid therapy. Tendon injury associated with fluoroquinolone use is significant, and risk factors such as renal disease or concurrent corticosteroid use must be considered when these agents are prescribed.

[Pefloxacin in the treatment of patients with mucoviscidosis]. / Mesto pefloksatsina v lechenii bol'nykh mukovistsidozom.

It was shown that microbial flora isolated from the bronchial secretion of 39 patients with mucoviscidosis in 1999-2001 consisted in one third (32.8%) of S. aureus strains. Evaluation of pefloxacin efficacy in the case of monoinfection and pathogens association revealed potent antistaphylococcal effect of the drug. Positive result was demonstrated in 82.3% cases by the 7th day. Among the side effects dominated arthropathy which disappeared at the period from 3 days to 3 months after drug administration was stopped.

[Comparative efficacy and safety of ciprofloxacin, ofloxacin, and pefloxacin in treatment of respiratory infections in children with cystic fibrosis]. / Sravnitel'naia éffektivnost' i bezopasnost' tsiprofloksatsina, ofloksatsina i pefloksatsina pri lechenii infektsii dykhatel'nykh putei u detei s mukovitsidozom.

Data on comparative investigation of the clinical and bacteriological efficacy and tolerability of monofluoroquinolones ciprofloxacin, ofloxacin and pefloxacin are given. The results confirm good clinical efficacy of all three monofluoroquinolones and high antistaphylococcal activity of pefloxacin. Efficacy of monofluoroquinolones against P. aeruginosa and S. maltophilia was moderate--only isolation of bacteria from spetrum became lower. Tolerability of monofluoroquinolones was good. Only at 5 patients the drugs use was stopped (4 in the ciprofloxacin group and 1--in the pefloxacin group). At 2 patients it was caused by arthropathy which was drug- and age-dependent. Quinolone-arthropathy was more often in the pefloxacin group and was registered only at the children elder than 10 years old with arthrological anamnesis. This arthropathy differed from experimental one by positive outcome and full recovery in the period from 7 days to 3 months. Results of morphological investigation confirmed clinical data--no invalidizing cartilage damage was revealed.

Pefloxacin and ciprofloxacin increase UVA-induced edema and immune suppression.

BACKGROUND: Quinolone antibiotics are popularly prescribed antibiotics because of their wide antibacterial spectrum and lowered bacterial resistance. Quinolone antibiotics are one of the well-known photosensitizers that induce phototoxicity. Their role in photocarcinogenesis has been suggested in some studies. MATERIAL AND METHODS: Mice were treated with two quinolone antibiotics (ciprofloxacin, which is less phototoxic, and pefloxacin, which is more phototoxic) to study the effect of the antibiotics on sunburn and immune suppression by ultraviolet A (UVA) irradiation. The effects of a combined treatment with UVA and these quinolone antibiotics were measured on back skin swellings, sunburn cell formations, depletion of epidermal Langerhans cells, and local and systemic suppression of contact hypersensitivity. RESULTS: Mice treated with both UVA and quinolone showed significantly increased back skin swellings and decreased epidermal Langerhans cells than mice treated with UVA only. Sunburn cells were increased significantly in mice treated with pefloxacin and 50 J/cm2 of UVA. Combination of pefloxacin and UVA suppressed local contact hypersensitivity significantly, but not systemic contact hypersensitivity. CONCLUSION: Phototoxic quinolones augmented the effect of UVA by increasing sunburn and apoptosis, depleting Langerhans cells and suppressing local immune response. By affecting apoptosis and immune suppression, they may facilitate photocarcinogenesis caused by UVA.

[Study of pefloxacin concentration in blood and sputum in the aged pneumonia patients with impairment of renal function].

OBJECTIVE: To study the drug concentration in blood and sputum, clinical effect and drug toxicity of pefloxacin in the aged pneumonia patients with different degree of impairment of renal function. METHODS: The patients were divided into four groups according to the impairment of renal functions pefloxacin 400 mg/12 h venous inflow, period of treatment is 10 days. Clinical manifestation and experimental index were registered; the drug concentration in blood and sputum was measured with biochemical technique, then compared and analyzed. RESULTS: The drug concentration in blood and sputum in four groups differed from the degree of the impairment of renal function. The concentration of drug in blood and sputum of the normal renal function was close to that in the low-grade impairment of renal function. Their clinical effective ratios were 83%, 80%, bacterium cleanup ratio was 86%. The difference of drug concentration in blood and sputum in the severe impairment of renal function was greater than that in the moderate renal function group, their clinical effective ratios were 66%, 53%, bacterial cleanup ratios were 57%, 36%, adverse reaction was growing along with degree of impairment of renal function. This drug has renal toxicity for moderate and severe impairment of renal function. CONCLUSION: In case of moderate impairment of renal function, prolongation of dose interval should be considered; pefloxacin should be avoided in severe impairment of renal function.

[Effectiveness of combined vancomycin and pefloxacine in gastrointestinal decontamination for preventing infections after chemotherapy-induced bone marrow aplasia. A randomized double-blind study]. / Intérêt d'associer la vancomycine à la péfloxacine en décontamination digestive pour la prévention des infections après chimiothérapie aplasiante. Etude randomisée en double insu.

OBJECTIVE: To test the value of the combination of pefloxacin and vancomycin as gastro-intestinal tract decontamination for the prevention of infections in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Oral pefloxacin plus vancomycin (48 patients), pefloxacin alone (51 patients), or placebo (52 patients) were administered in a randomized double-blind study. Evaluation was done by determining site and documentation of infections, organisms responsible for bacteriologically documented infections, organisms acquired in surveillance cultures and number of days with fever during aplasia. RESULTS: Patients receiving pefloxacin had significantly fewer episodes of bacteremia with enterobacteriacae. No differences were noted between patients treated by pefloxacin and those who received a combination of pefloxacin with vancomycin regarding gram-positive (Gram+) infections and infections with gram-negative (Gram-) organisms usually resistant to pefloxacin. However, placebo gave similar results. There was no induction of resistance to pefloxacin during the study. Tolerance of treatment was excellent. Only a prolonged aplasia has been observed in patients receiving pefloxacin. CONCLUSION: Thus, the combination of vancomycin with pefloxacin was not more efficacious than pefloxacin only for the prevention of Gram+ infections in the neutropenic patient. The systematic use of antibiotics as gastrointestinal tract decontamination for the prevention of infections in patients with aplasia may be questionable.

Lansoprazole and secnidazole with clarithromycin, amoxycillin or pefloxacin in the eradication of Helicobacter pylori in a developing country.

BACKGROUND: A number of triple drug regimens using proton pump inhibitors and two antibiotics have been evaluated in the West and reported to achieve Helicobacter pylori eradication rates of over 90%. In developing countries however, these combinations have neither been well evaluated, nor the optimum treatment for H. pylori infection well defined. AIM: To compare the combination of a proton pump inhibitor with a nitroimidazole and another antibiotic in eradicating H. pylori infection and healing duodenal ulcer. METHODS: Sixty consecutive patients with active duodenal ulcer who were positive for H. pylori (by rapid urease test and 14C-urea breath test) were randomized into three treatments groups: (1) LAS (n=21): lansoprazole 30 mg o.m., amoxycillin 500 mg q.d.s. and secnidazole 2 g on alternate days for 2 weeks; (2) LCS (n=18): lansoprazole 30 mg o.m., clarithromycin 500 mg b.d. and secnidazole 2 g on alternate days for 1 week; (3) LPS (n=21): lansoprazole 30 mg o.m., pefloxacin 400 mg o.m. and secnidazole 2 g on alternate days for 2 weeks. Urease and breath tests were performed at 0, 6 and 12 weeks to check for H. pylori eradication. RESULTS: Intention-to-treat eradication rates were as follows: LAS 86%, LCS 83%, LPS 71%; the overall ulcer healing rate was 90% at 6 weeks. CONCLUSIONS: High H. pylori eradication rates were achieved using the amoxycillin- and clarithromycin-based therapies. Fewer side-effects, better compliance and low cost favoured the amoxycillin-based therapy.

Urine bactericidal activity of pefloxacin versus norfloxacin in healthy female volunteers after a single 800-mg oral dose.

In an open randomised crossover study the antibacterial activity of pefloxacin and norfloxacin was assessed in the urine after a single 800-mg oral dose in 14 healthy female volunteers. Pefloxacin demonstrated lower peak concentrations in the urine than norfloxacin (mean, 217.2 mg/l versus 492.9 mg/l as determined by the microbiological assay) but pefloxacin was present over a longer period of time in sufficient concentrations than norfloxacin. Mean urine levels of at least 2 mg/l were present for 7 days after pefloxacin administration and 2 days after norfloxacin administration as determined by the microbiological assay. Overall, the urinary recovery of pefloxacin and norfloxacin amounted to 49.3% and 25.1%, respectively, of the total administered dose. The average urine bactericidal activity against the five test organisms was as follows: against reference strain Escherichia coli ATCC 25922 susceptible to nalidixic acid (Nal-S) for 5 days with pefloxacin and 2 days with norfloxacin; against three clinical isolates, one strain each of E. coli resistant to nalidixic acid (Nal-R), Klebsiella pneumoniae Nal-R, and Staphylococcus saprophyticus, for 3 days with pefloxacin and 24 h with norfloxacin; and against a clinical isolate of Enterococcus faecalis for 2 days with pefloxacin and 12 h with norfloxacin. In conclusion, pefloxacin as a single dose proved to have sufficiently high and long-lasting urine bactericidal activity against urinary pathogens. These findings support the results of a meta-analysis of seven clinical trials in patients with uncomplicated lower UTI, demonstrating a single oral dose of 800 mg pefloxacin to be as effective as a conventional treatment with comparative drugs.

[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.

Inhibition of rat parotid gland growth response induced by chronic isoproterenol following treatment with quinolone antibiotics.

While antibiotics are broadly used in dental and medical therapy, little attention has been directed towards the potential toxic side effects of antibiotics on tissue regeneration. Here we examined the effect of a quinolone antibiotic, pefloxacin (Rhone Poulenc) on rat parotid gland responses to chronic isoproterenol treatment. Groups of rats received injections of isoproterenol to induce glandular growth, saline (controls), pefloxacin, or isoproterenol and pefloxacin in combination. Parotid gland weight decreased significantly after pefloxacin treatment for 7 days as well as inhibiting glandular enlargement provoked by isoproterenol. The same trend was observed for the rates of DNA synthesis, with the incorporation of [3H]-thymidine in isoproterenol/pefloxacin-treated rats reduced to 49% of isoproterenol treatment alone levels. Saline-treated animals were 42% of the rate of [3H]-thymidine incorporation into DNA observed in isoproterenol treated rats. While isoproterenol treatment increased steady-state mRNA levels for fos, jun, myc, src, c-erbB-2, ras and topo II, inclusion of pefloxacin with the isoproterenol regimen blocked these increases. Pefloxacin treatment by itself did not alter proto-oncogene mRNA levels in the parotid gland. Glandular amylase activity was decreased in the pefloxacin treated group, while the combination of isoproterenol with pefloxacin did not decrease glandular amylase levels to the extent of that observed with beta-agonist treatment alone. In acute experiments, pefloxacin significantly decreased the volume of saliva secreted by the parotid gland. These results suggest that quinolone-based antibiotics disturb the secretory function of the parotid gland and can inhibit cell proliferation and regeneration.

Clinical and microbiological evaluation of pefloxacin in lower respiratory tract infections.

Patients with Gram-negative lower respiratory tract infections (acute exacerbation of chronic bronchitis (n = 23), pneumonia (n = 4), and bronchiectasis (n = 5) were treated with pefloxacin, 400 mg twice daily, given either intravenously or orally. Symptoms, signs and sputum volume and colour were monitored daily. Chest X-rays, sputum culture and Gram-stain examinations were carried out on days 1 and 5, and immediately after the end of the treatment. There was a clinical improvement, as indicated by the incidence of cough, dyspnoea and rales, and by sputum volume and colour in 31 patients (97%). Microbiological improvement, as indicated by the complete elimination of sputum pathogens and pus cells, was achieved in 28 of the patients (88%). In one patient, an adverse effect, renal failure, occurred. These results suggest that pefloxacin is both clinically and microbiologically effective for the treatment of Gram-negative lower respiratory tract infections.