Use of norfloxacin to treat chronic typhoid carriers.

High relapse rates and low tolerability to ampicillin characterize present therapy for carriers of Salmonella typhi. Norfloxacin, a carboxyquinolone with a 90% minimum inhibitory concentration for S. typhi of less than or equal to 0.5 micrograms/mL, is a promising alternative. Carriers of S. typhi were treated in a double-blind trial with either norfloxacin (400 mg) or matching placebo given every 12 h for 28 d. Twelve assessable individuals were treated in each group. After therapy, 11 of 12 individuals treated with norfloxacin had negative stool and bile cultures for S. typhi. All placebo-treated carriers still had positive cultures immediately after therapy. Subsequently, 11 individuals were treated openly with norfloxacin. S. typhi was eradicated in seven of 11. Overall, the eradication rate for 23 individuals treated with norfloxacin was 78%. Eighteen individuals were followed up for one year, and their stool and/or bile cultures remained negative. From our results, norfloxacin is an effective and well-tolerated antimicrobial agent for eradicating the chronic typhoid carrier state.

Norfloxacin: review of safety studies.

The tolerability profile of norfloxacin, the first of a new generation of fluoroquinolone carboxylic acid antibacterials, has been defined in numerous laboratory animal and human trials. Whether administered for moderate or protracted periods, norfloxacin has been relatively safe in animals over a wide range of doses. There has been no evidence of a teratogenic effect in any of the animal species tested (rat, rabbit, mouse, monkey) at six to 50 times the human dose (400 mg twice daily). However, norfloxacin has been shown to produce embryonic loss in monkeys when given in doses 10 times the maximal human dose, resulting in peak plasma levels that are two to three times those obtained in humans. Although there are no adequate and well-controlled studies in pregnant women, norfloxacin is not recommended for use in this population because it, like other drugs in this class, causes arthropathy in immature animals. In animals, norfloxacin is neither mutagenic nor carcinogenic, and, in clinical trials, norfloxacin-related adverse experiences have been uncommon. Those that have occurred have been generally mild, requiring discontinuation of therapy in less than 1 percent of patients. The most frequently reported side effects have been nausea, dyspepsia, headache, and dizziness. Administration of 400 mg of norfloxacin at two or three times a day has been associated with reasonably good gastrointestinal tolerance.

Norfloxacin in the treatment of urinary tract infections in men with and without identifiable urologic complications.

A retrospective analysis of data from the treatment of 95 men with nonbacteremic urinary tract infections (UTIs) (clean-catch urinary bacterial count greater than or equal to 10(5) colony-forming units/ml) who received norfloxacin (400 mg orally twice daily) was performed. Treatment duration ranged from a required minimum of seven days to a maximum of 30 days. If an underlying anatomic or functional condition existed that might decrease the likelihood of a favorable medical response and/or require prolonged treatment, the patient's UTI was considered "complicated." In addition to eight patients with polymicrobic UTIs (usually involving enterococci or Pseudomonas aeruginosa), 48 men (i.e., 51 percent of the total population) had an identifiable complication. Complications included benign prostatic hypertrophy in 13 patients; prostatic cancer in four; urethral stricture in four; quadriplegia/paraplegia with indwelling urinary catheter in four; prostatism in three; and other conditions commonly recognized as altering the response to antibiotic treatment. Among the 95 patients treated, 76 (80 percent) were considered to have had a cure and five (5 percent) showed improvement. Fourteen patients (15 percent) failed to show a response to treatment. Of the 48 patients with UTI and defined complications, 36 (75 percent) had a cure, three (6 percent) showed improvement, and therapy failed in nine (19 percent). Ninety-seven percent (105 of 108) of the pretreatment bacterial isolates were susceptible to norfloxacin. In addition to the three resistant organisms that were present prior to therapy, three organisms (two P. aeruginosa and one Enterobacter) persisted and acquired resistance during therapy. Five adverse clinical experiences and six adverse laboratory experiences were noted. Only one of the former (mild heartburn) was thought to be drug related, and no adverse experience was considered serious or required discontinuation of treatment. Gastrointestinal tolerability of oral norfloxacin was good.

Treatment of urinary tract infection with norfloxacin. Analysis of cost.

Twenty-five patients with urinary tract infection were treated with norfloxacin, a fluoroquinolone antibacterial with a wide spectrum of activity for an oral agent. Of 22 patients who were evaluable, 20 had complicated urinary tract infection; infection was cured in 19 patients at one week after treatment. Optimal alternative treatments were also selected in norfloxacin's stead, based on each patient's characteristics and the results of susceptibility testing for each isolated pathogen. Direct costs for alternative treatment ranged from $7 to $970. The results indicated that for those patients with suspected or proven urinary tract infection caused by multiresistant bacteria, therapy with norfloxacin may represent a cost-effective choice.

Use of norfloxacin in the treatment of acute diarrheal disease.

In studies conducted in seven countries, 392 persons with acute diarrhea were enrolled and randomly assigned to one of three regimens. In order to compare the effectiveness of various therapies for acute gastroenteritis, patients were treated for five days with either norfloxacin, 400 mg twice daily, norfloxacin, 400 mg three times a day, or trimethoprim/sulfamethoxazole, (160 mg/800 mg) twice daily. Clinical cure occurred in 89 percent (lower dose) and 91 percent (higher dose) of those treated with norfloxacin, compared with 78 percent of those receiving trimethoprim/sulfamethoxazole; cure rates in each treatment group were greater when the patient's stool contained fecal leukocytes. In 105 of 106 (99 percent) patients treated with either dose of norfloxacin and in 49 of 52 (94 percent) trimethoprim/sulfamethoxazole-treated subjects, the bacterial enteropathogen identified in the pretreatment stool was eradicated on the posttreatment specimen. Two percent (two patients) of those receiving the lower dose of norfloxacin, 3 percent (two patients) of those receiving trimethoprim/sulfamethoxazole, and 4 percent (three patients) of those receiving the higher dose of norfloxacin experienced minor and transient adverse hematologic or blood chemistry reactions. In addition, mild cutaneous reactions that were attributed to the study medications developed in two patients receiving the higher dose of norfloxacin and in three patients who received trimethoprim/sulfamethoxazole. These studies indicate that norfloxacin is safe and effective therapy for bacterial diarrhea.

Norfloxacin versus co-trimoxazole in the treatment of recurring urinary tract infections in men.

Norfloxacin is a lipid-soluble weak organic acid bound to plasma proteins to a low extent. Norfloxacin has a pKa1 from 6.2 to 6.4 and a pKa2 from 8.7 to 8.9. Mean concentrations of norfloxacin in prostatic tissue have been reported as 1.7 mg/kg. Recurrent urinary tract infection (UTI) in men is frequently associated with prostatic infection, and chronic prostatitis is both difficult to diagnose and to treat. One hundred and twenty-nine patients were entered into a randomized, open controlled, comparative multiclinic study of the efficacy and safety of norfloxacin vs. co-trimoxazole in male patients with recurrent UTI. Norfloxacin 400 mg and co-trimoxazole 160/800 mg were given twice daily for 4 to 6 weeks. One hundred and nine patients were considered evaluable for efficacy. Norfloxacin effected bacteriologic eradication in 56 of 60 (93%) patients; co-trimoxazole effected eradication in 39 of 49 (67%) patients. This difference in bacteriologic outcome had statistical significance (p less than 0.05). A subset of these patients had prostatic fluid cultures pre- and post-therapy. The eradication rate was 23 of 25 (92%) for norfloxacin and 10 of 15 (67%) for co-trimoxazole. Bacteria isolated were (norfloxacin/co-trimoxazole): E. coli 27/25; K-E-S 14/13; Proteus spp. 7/5; Ps. aeruginosa 2/0; other gram-negative bacilli 4/3; gram-positive cocci 7/3. Four patients, one on norfloxacin and three on co-trimoxazole had drug-related clinical and/or laboratory adverse experiences. None was serious. Norfloxacin appears to be an effective drug for the treatment of recurrent UTI in men.

World-wide clinical experience with norfloxacin: efficacy and safety.

This review covers 2346 norfloxacin treated patients in clinical trials world wide. These studies show that 400 mg of norfloxacin b.i.d. was effective and compared favorably with other standard oral agents in the treatment of urinary tract infections, including complicated and recurrent infections in men. This regimen given b.i.d. or t.i.d. was also effective in the treatment of acute gastroenteritis due to common gastrointestinal pathogens such as enterotoxigenic Escherichia coli, Salmonella spp., Shigella spp., Campylobacter spp. as well as less common organisms. A single 800 mg dose was effective in the treatment of gonorrhoea including patients with extra genito-urinary involvement and penicillinase producing strains of Neisseria gonorrhoeae. Preliminary data from ongoing trials have also shown that norfloxacin is effective in the prophylaxis of traveller's diarrhoea and infections in the granulocytopenic patient. These various regimens of norfloxacin were well tolerated with a low incidence (less than 3%) of drug related adverse experiences. The most common adverse experiences were nausea, headache, dizziness, rash, elevation of liver enzymes and eosinophilia.

Multiclinic comparative study of norfloxacin and trimethoprim-sulfamethoxazole for treatment of urinary tract infections.

Three hundred seventy patients with upper or lower urinary tract infections were entered into a multicenter, open comparative study. A total of 190 patients were treated with norfloxacin, and 180 patients were treated with trimethoprim-sulfamethoxazole. The percentage of strains susceptible to norfloxacin (99%) was significantly greater (P less than 0.001) than the percentage of strains susceptible to trimethoprim-sulfamethoxazole (90%). The percentages of patients with bacteriological outcomes of eradication were greater in the norfloxacin group (97%) than in the trimethoprim-sulfamethoxazole group (90%). The difference was significant (P less than 0.05). Seven patients (three treated with norfloxacin, four treated with trimethoprim-sulfamethoxazole) experienced early reinfection. Of 370 patients entered into the study, 20 patients experienced clinical adverse effects that were probably or definitely related to the study drug; 6 patients were in the group that received norfloxacin, and 14 were in the group that received trimethoprim-sulfamethoxazole. Study antimicrobial agents were discontinued because of clinical adverse effects in eight patients (norfloxacin, one patient; trimethoprim-sulfamethoxazole, seven patients). Three patients receiving norfloxacin and four patients receiving trimethoprim-sulfamethoxazole had laboratory adverse effects which were classified as probably or definitely drug related. None of the clinical or laboratory adverse effects was serious.

Anaerobes in liver abscess.

Non-spore-forming anaerobic bacteria are recognized as the most numerous and important pathogens in pyogenic liver abscess. These infections are usually polymicrobial. Frequent causes of anaerobic liver abscess are acute and chronic inflammatory bowel disease with or without perforation, malignancy and/or surgery of the gastrointestinal tract or pelvic organs, and biliary tract disease. Many abscesses are still classified as cryptogenic. A thorough understanding of bacterial etiology and the use of refined and accurate localizing and diagnostic techniques facilitate early diagnosis and effective treatment. In addition, the availability of bactericidal antimicrobial agents with extended spectra of activity against anaerobes and their use in selected cases is changing the classic therapeutic approach of antimicrobial therapy and open surgical drainage. Percutaneous aspiration has been used successfully in lieu of open drainage in several cases and antimicrobial treatment without drainage has been successful in others.

Comparative clinical evaluation of azlocillin and gentamicin.

Forty-four patients with severe systemic bacterial infection were treated with azlocillin (20) or gentamicin (24). The commonest sites of infection were skin and soft tissue, lungs and bone. Thirty-eight patients had received previous antimicrobial therapy. The commonest infecting organism was Pseudomonas aeruginosa. The overall response rate in the azlocillin group was cure or partial cure in 18 patients and failure in one patient, and in the gentamicin group 15 cures or partial cures and six failures. Four patients, one on azlocillin and three on gentamicin, could not be evaluated. Azlocillin was an effective and safe therapy for the treatment of Ps. aeruginosa infections.

Nocardiosis pulmonar en Guatemala: primer caso confirmado. / Pulmonary nocardiosis in Guatemala: first confirmed case

Se presenta el primer caso de nocardiosis pulmonar en Guatemala, confirmado microbiologicamente por el aislamiento de Nocardia asteroides a partir de puncion pulmonar directa, y lesiones pustulosas en la cara. El paciente, oficinista de 53 anos de edad, consulto al medico por sintomatologia compatible con neumonia cronica o tuberculosis, la cual no cedio a pesar del tratamiento con diferentes antibioticos de amplio espectro y drogas antituberculosas.El diagnostico etiologico exacto permitio la administracion del tratamiento con sulfadiazina y trimetoprim-sulfametoxazol y revertir el proceso. No se logro detectar ningun factor predisponente a la infeccion o alguna deficiencia inmunologica en el paciente

Comparison of selective media for isolation of presumptive group D streptococci from human feces.

Pfizer Selective Enterococcus (PSE) agar, a medium containing bile, sodium azide, and esculin, was evaluated for its sensitivity and selectivity for detection and enumeration of presumptive group D streptococci in human feces. SF broth and SF broth plus agar (1.5%), representing selective media in common use, were studied simultaneously. Presumptive group D streptococci were recovered on PSE agar from the feces of all 25 subjects. No growth was observed in 8% of specimens in SF broth. No gram-negative organisms were recovered in any medium. PSE agar has the advantages of selecting out Streptococcus bovis, earlier appearance of distinctive reactions, and lack of requirement for special incubation temperature.

Effect of dosage and route of inoculation upon antigenicity of inactivated influenza virus vaccine (Hong Kong strain) in man.

Earlier studies on the antibody response to inactivated influenza vaccines injected by different routes have given contradictory results, some suggesting that 0.1 ml intradermally is superior to 1.0 ml subcutaneously, others suggesting the opposite. With the advent of the 1968-69 Hong Kong influenza epidemic it seemed worth while to re-evaluate whether a smaller intradermal dose would elicit antibody responses comparable to those following a larger subcutaneous dose.A study was performed evaluating 3 doses: 0.1 ml (65 CCA), 0.25 ml (160 CCA), and 0.5 ml (320 CCA) of zonal-purified vaccine. The 0.1-ml dose was administered by both routes, and the other doses subcutaneously only. The effect of "booster" inoculation by the same route 2 and 4 weeks later was also studied. Sera were examined for haemagglutination-inhibiting antibody, and antibody response was determined by the percentage showing 4-fold or greater titre rises and by increase in geometric mean titre.The antibody response to the first inoculation was highest in the 0.1-ml intradermal groups and the lowest in the 0.1-ml subcutaneous groups. All groups receiving a second inoculation 2 weeks after the first experienced an increase in antibody response; responses to the second inoculation given 4 weeks after the first were variable. Considering the over-all effect of all combinations of doses and routes, the intradermal groups appeared to achieve the best antibody response and the 0.1-ml subcutaneous groups the least.There appeared to be an inverse relationship between antibody response and pre-immunization antibody titre.The data show that, with vaccine of similar CCA content, 0.1 ml intradermally would be a reasonable alternative to, and perhaps better than, the usual 0.5-ml subcutaneous dose. The limitations of this approach are discussed.