Effect of short-term therapy with ciprofloxacin, ceftriaxone and placebo on human peripheral WBC and marrow-derived granulocyte-macrophage progenitor cells (CFU-GM)
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Publications and source records attributed to S Segev.
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OBJECTIVE: To assess the prevalence of sexually transmitted pathogens in drug-addicted women in Tel Aviv, Israel. DESIGN: A prospective study conducted between March and July 1987. SETTING: A methadone clinic in Tel Aviv, Israel. SUBJECTS: Sixty four asymptomatic female drug addicts were studied; 38 of them were declared practising prostitutes. METHODS: Cervical specimens were obtained for cultures, and blood samples were drawn for serological tests. Demographic data and sexual histories were obtained using a standard questionnaire. RESULTS: Chlamydia trachomatis was detected in the cervix of 25% of women; 98% had antibody titres (greater than 1:64). Mycoplasma hominis and Ureaplasma urealyticum were isolated in 57% and 65% respectively. Gardnerella vaginalis was detected in 17% of women, and herpes simplex virus was cultured from two prostitutes. Five per cent of women were carriers of HBsAg, while 57% had HBSs and/or HBc antibodies. Only one prostitute had specific treponemal antibodies. In no case were gonococci or group B streptococci isolated, and HIV serology was invariably negative. CONCLUSION: Chlamydia and genital mycoplasmas appear to be the prevailing pathogens in Israeli drug-addicted women, while gonococci and Treponema pallidum occur only rarely.
To evaluate the penetration of ciprofloxacin, a new wide-spectrum oral antibiotic, into the vitreous, ciprofloxacin was administered orally to 21 patients who were scheduled to undergo vitreal surgery. Seven patients received 750 mg ciprofloxacin 4 hr before surgery (group I), seven patients received this dose 8 hr before surgery (group II), and seven patients received two 750-mg doses of oral ciprofloxacin every 12 hr. The last dose was administered 12 hr before surgery (group III). Vitreous and blood samples were collected simultaneously and assayed for ciprofloxacin concentrations by bioassay and high-performance liquid chromatography.
Sixteen patients with acute meningitis caused by Gram-negative bacteria were treated with pefloxacin intravenously. The age range of the patient group was six months to 85 years with a mean age of 40 years; three patients were children. In all but two patients meningitis was a complication of neurosurgical operations and fourteen of the sixteen had received prior therapy which was not successful. The causative organisms were: Pseudomonas aeruginosa (5), Acinetobacter calcoaceticus (4), Klebsiella pneumoniae (3), Enterobacter cloacae (2), Citrobacter diversus (1) and Salmonella group C (1). Pefloxacin was administered intravenously 800 mg twice a day to the adult patients (mean dosage of 21( +/- 6.7) mg/kg body weight) for a mean period ( +/- S.D.) of 11( +/- 4) days. The mean cerebrospinal fluid concentration of pefloxacin was 8.8( +/- 5.0) mg/l which was 54% of the mean peak serum concentration (16.3( +/- 8.8]. The mean MIC and MBC of the causative organisms were 1.1( +/- 1.2) mg/l and 1.64( +/- 1.2) mg/l. Thirteen patients (87%) were cured or clinically improved and twelve (80%) were bacteriologically cured. One patient failed, another patient had reinfection and one was not assessable. No side effects were observed. In the present study pefloxacin offered an efficacious and safe treatment of Gram-negative meningitis following failure of other antibiotic therapy.
Soft tissue infections in compromised patients are frequently caused by Gram-negative organisms and particularly by Pseudomonas aeruginosa. These pathogens are effectively eradicated by pefloxacin as well as by ceftazidime. The effectiveness and safety of these two agents were compared in a prospective randomized study in 67 patients with soft tissue infections. Underlying conditions included malignant diseases, diabetes mellitus and chronic renal failure. The infections included: post operative infection, septic foot, soft tissue abscess and cellulitis. Thirty-three patients were treated with intravenous ceftazidime for a mean duration of ten days. More than half the 34 patients given pefloxacin were treated only orally for a mean period of 13 days. The clinical and bacteriological outcomes were similar in both groups. There was clinical cure or improvement in 26 pefloxacin cases and in 23 ceftazidime cases, failure in six pefloxacin cases and in seven ceftazidime and relapse in two pefloxacin and in three ceftazidime patients. The bacteriological responses were eradication in 23 pefloxacin cases and in 22 ceftazidime cases, persistence in five pefloxacin cases and in six ceftazidime cases, relapse in one pefloxacin case and in none of the ceftazidime group, reinfection in four pefloxacin cases and in three ceftazidime cases and there was one unassessed patient in the pefloxacin group and two in the ceftazidime group. Nausea and vomiting occurred in three patients and elevation of liver enzymes in another patient; all side effects were observed only in the pefloxacin treated patients. These results suggest that oral pefloxacin could offer an alternative to intravenous ceftazidime in half the compromised patients with tissue infections. However, adverse reactions due to pefloxacin administration should be watched for during such therapy.
Ofloxacin is highly active against most pathogens causing bacterial enteritis. High faecal levels are achieved readily following a single oral dose and may persist for up to five days despite partial binding by faeces. In addition, adequate ofloxacin levels persist in pancreatic secretions and bile for 12 to 14 h following oral administration. Clinical data from various centres demonstrate a prompt response when ofloxacin is administered once-daily for shigellosis, salmonellosis and various other enteric pathogens. These theoretical observations and clinical data suggest a potential for once-daily oral ofloxacin therapy for bacterial diarrhoea.
Ten patients with acute meningitis caused by gram-negative bacteria were treated with pefloxacin intravenously for a mean period of 10 days. Eight patients responded clinically to pefloxacin treatment, and the causative organisms were eradicated from the cerebrospinal fluid in 9 of the 10 patients. Pefloxacin may offer a new, efficacious, and safe therapy for gram-negative meningitis.
A cohort of 127 nursing home residents aged 60-98 years were vaccinated during the winter of 1985-86 with the A-Chile 1/83 (C), A-Philippines 2/82 (P), and B-USSR (B) commercial influenza vaccines. Before vaccination 40%, 23%, and 69% were susceptible to influenza Ac, Ap, and B, respectively [hemagglutinin inhibition (H.I.) titer less than 1:40]. One month following initial vaccination, 32 patients [25%] remained unprotected against two or all three vaccine strains. These patients were revaccinated with the same influenza vaccine and followed up. At five months 11%, 19%, and 23% of the initial cohort were still unprotected against Ac, Ap, and B strains, respectively. We conclude that two conventional influenza vaccines administered one month apart leave unprotected 30% of healthy elderly people who are initial influenza vaccine failures.
Antibiotic cost information was added to the computerized print-out for each patient of microbiology culture results, next to the antibiotic susceptibility list. During the first six months of this addition, the average monthly cost of antibiotics decreased by 16.5% ($7636) compared to the 12 months period preceding the study period. The average antibiotic cost per admission decreased by 15.7% ($1.61) and the average antibiotic cost/hospital day decreased by 10.6% ($0.23). Antibiotic savings were highest in the Department of Obstetrics and Gynaecology (21.7%) and lowest in the Department of Paediatrics (10.8%). Two-thirds of the average savings were initiated by the house-staff and the remainder by infectious disease consultants. The effect of this system on the level of medical care remains to be studied.
Twenty-five male patients with nongonococcal urethritis including 15 chlamydial infections, were treated with spiramycin for ten days. All but four patients had been treated previously, mostly with tetracyclines. Chlamydia trachomatis was cultured in seven patients and was detected in three additional men by immunofluorescent smear. Five other patients had antibodies to chlamydia, and one patient yielded a positive culture for Ureaplasma urealyticum and Mycoplasma hominis. A successful clinical response was observed in 64% of the patients; C. trachomatis was eradicated from six of seven patients with positive cultures and the three positive direct smears were negative after treatment. It is concluded that spiramycin can be used effectively for the therapy of acute nongonococcal urethritis, as well as in patients who have failed to respond to previous treatment with tetracyclines and erythromycin.
Epileptic seizures and hallucinations, which are rare in patients receiving quinolones, have been observed more frequently in patients receiving both quinolones and either theophylline or nonsteroidal anti-inflammatory drugs. Inhibition of gamma-aminobutyric acid (GABA) binding to the GABA receptor, resulting in general excitation of the central nervous system, may be the underlying mechanism of these adverse phenomena. We demonstrate here that ciprofloxacin displaced a GABA-like substance (muscimol) from the GABA receptor when administered in concentrations of greater than 10(-4) M. These concentrations were lower than those needed by pefloxacin, ofloxacin, and nalidixic acid to reach a concentration that inhibits 50% of binding. The combination of ciprofloxacin and theophylline was additive in reducing the level of muscimol binding to the GABA receptor, whereas a diclofenac-ciprofloxacin combination had no effect. The concentrations of both ciprofloxacin and the other quinolones used were much higher than those observed in human serum and cerebrospinal fluid in a clinical setting; however, different human GABA receptor affinities, preexisting GABA excitation, or underlying central nervous system disease may amplify the excitatory side effects observed by the co-administration of quinolones and theophylline. Attention should be paid to the possible epileptogenic activity of the simultaneous administration of quinolones with aminophylline, nonsteroidal anti-inflammatory drugs, or other unpredictable drugs.
One hundred and fourteen hospitalized patients with moderate or severe infections were assigned at random, in four medical centers, to receive either ceftizoxime or cefotaxime, administered intravenously in a dosage of 1 to 2 g every 8 h. Of 96 patients evaluable for efficacy, 24 (25%) had bacteremia, 46 (48%) had urinary tract infections and 9 (9%) had pneumonias. Half the patients had been treated ineffectively by other antibiotics prior to the study drug treatment. The overall clinical efficacy was 90% in both treatment groups and 83% in both groups with bacteremia. All patients with urinary tract infection were cured by both agents. Bacteriological eradication rate was 95% in both groups. Adverse reactions, though mild, were more frequent in the cefotaxime group (13.5%) than in the ceftizoxime group (6.8%); superinfection rate was higher in the ceftizoxime group. Both antibiotics were highly and equally efficacious in the therapy of severe infections in hospitalized patients.
A 37-year-old patient with acute nonlymphatic leukemia developed gastrointestinal phycomycosis during failure in bone marrow production. The clinical presentation was of acute typhlitis. Laparotomy revealed a necrotic mass in the region of the iliocecal valve, and on histologic examination hyphae of phycomycetes with invasion of the blood vessels were seen. The patient died as a result of widespread infection.
Q fever endocarditis occurs in up to 11% of patients infected by Coxiella burnetti. Major clues for the diagnosis are culture-negative endocarditis, hepatic involvement, rash, and thrombocytopenia. Characteristically, the diagnosis is delayed. In our patient, Q fever endocarditis occurred without previously recorded signs of infection. Fever, rash, and hepatic involvement all occurred following aortic valve replacement. The histologic picture of the excised valve was consistent with endocarditis, and serologic tests disclosed elevated IgA and IgG antiphase 1 antibody titers against C burnetti, compatible with Q fever endocarditis. It is assumed that the exacerbation of quiescent Q fever endocarditis was caused by cardiac surgery and steroid therapy.
Interactions between ciprofloxacin and other non-antibiotic agents occur; some can be predicted from in vitro results and general pharmacodynamic rules, whereas other interactions appear to be unpredictable. In the absorptive phase, neither food nor ranitidine, a histamine (H2)-receptor blocker, alters the absorption of ciprofloxacin. Pirenzipine, a cholinergic agent, and N-butyl-scopolaminium bromide delay the absorption of ciprofloxacin, whereas metclopramide accelerates absorption. Both magnesium- and aluminum-containing antacids significantly decrease the absorption of ciprofloxacin, probably through formation of a chelate complex. Patients receiving ciprofloxacin and theophylline simultaneously have higher serum theophylline levels than do recipients of theophylline alone. The interaction is probably due to the inhibition by ciprofloxacin of hepatic microsomal enzymes that metabolize theophylline. Ciprofloxacin does not displace bilirubin from albumin; thus, interactions resulting from displacement of highly protein-bound agents by ciprofloxacin are unlikely. Ciprofloxacin and other quinolones inhibit gamma-aminobutyric acid receptors through reduction of their binding capacity and thus may potentiate convulsions induced by other agents. Cimetidine, a cytochrome P450 antagonist, affects metabolizable quinolones, and it is likely that it may affect ciprofloxacin's disposition after prolonged use. Currently, the only clinically significant interactions are the inactivation of ciprofloxacin by antacids and an increase in theophylline blood levels in the presence of ciprofloxacin. In the future, attention should be paid to other possible interactions.
A neutropenic patient with acute myeloid leukemia developed nasal and perinasal infection caused by the fungus Exserohilum rostratum. Early amphotericin B treatment along with marrow recovery resulted in resolution of the infection. A review of other previously reported cases of Exserohilum and Bipolaris infections show a favourable outcome in most patients who receive systemic antifungal treatment with amphotericin B.
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