Ciprofloxacin therapy in cystic fibrosis.

There is great need for an oral agent that could be used to treat pulmonary exacerbations in patients with cystic fibrosis. In this study, the use of oral ciprofloxacin as sole therapy was evaluated in 18 patients with 39 infectious episodes; 13 episodes were classified as severe, 19 were classified as moderate, and seven were classified as mild. Patients ranged in age from eight to 36 years (mean, 23 years). Dosage varied according to severity of disease, body size, and the susceptibility of the Pseudomonas isolate to ciprofloxacin; the dose ranged from 750 to 2,250 mg daily (mean, 1,800 mg). Ten patients received one course of ciprofloxacin, and eight received repeated courses. The overall clinical response rate was 82 percent. There was a response to the initial treatment course in 96 percent of the patients. Those in whom therapy failed had been re-treated with ciprofloxacin and were severely ill. Failure to respond correlated poorly with pretreatment minimal inhibitory concentration (MIC) values (0.6 microgram/ml for failures versus 0.4 microgram/ml for responses). Pseudomonas could not be eradicated from the sputum of any of the patients, although there was a marked reduction in purulence and bacterial counts. In general, patients who did not require re-treatment for three months would again have susceptible organisms. When organisms became resistant to ciprofloxacin (MIC greater than 2 micrograms/ml), they showed no concomitant new aminoglycoside or beta-lactam resistance. No serious toxicity occurred in any of the 39 episodes of treatment. In seven patients treated with combination therapy (tobramycin or azlocillin), the infecting organisms were reduced in number, but eradication of Pseudomonas generally could not be achieved. Increases in MIC occurred during combination therapy. Ciprofloxacin is a major advance in the treatment of bronchopulmonary infection in patients with cystic fibrosis.

Treatment of serious infections with intravenous ciprofloxacin.

Thirty-four patients were treated with intravenous ciprofloxacin. Thirty infections occurring in 28 patients were assessable for the efficacy analysis. The drug dosage was 300 mg every 12 hours in 19 patients and 200 mg intravenously every 12 hours in nine patients. Twelve patients were also given ciprofloxacin orally after initial intravenous therapy. The mean duration of total therapy was 31 days. The overall clinical response rate was 87 percent, and the bacteriologic response rate was 70 percent. Favorable responses were observed in 10 of 12 patients with osteomyelitis/septic arthritis; seven of eight with soft tissue infection; four of four with pneumonitis; one of two with cystic fibrosis; and four of four with urinary tract infections. Resistance to ciprofloxacin developed in three Pseudomonas aeruginosa isolates. Toxicity was minor: phlebitis occurred in six patients, nausea in six, and rash in one. Intravenously administered ciprofloxacin or intravenous ciprofloxacin followed by oral ciprofloxacin is a safe and effective therapy for serious infections.

Effect of ciprofloxacin on fecal flora of patients with cystic fibrosis and other patients treated with oral ciprofloxacin.

Ciprofloxacin is a fluorinated carboxyquinolone that inhibits Enterobacteriaceae, staphylococci, and Pseudomonas at low concentrations. It has poor activity against Bacteroides fragilis. In this study, the effect of administration of ciprofloxacin on bowel flora was determined in patients treated for different infections. Patients, aged 22 to 70 years, were treated with 500 mg of ciprofloxacin every 12 hours or 750 mg every eight hours for seven to 42 days. Some patients had advanced cystic fibrosis; other patients had infections with resistant bacteria. Infecting organisms were Pseudomonas aeruginosa, Staphylococcus aureus, Serratia, and Acinetobacter. Sites of infections were lung, soft tissue, and urinary tract. Stool samples were evaluated initially, during therapy, and after therapy. No resistant gram-negative aerobic species emerged; five patients had yeast colonization, staphylococci were found in three patients, and streptococci were found in one patient. Ciprofloxacin did not select resistant gram-negative bacteria in the stool, although sputum isolates showed increases in minimal inhibitory concentrations. Resistant bacteria were not selected in the fecal flora of patients who had received beta-lactam and aminoglycoside antibiotics before therapy with ciprofloxacin.

Oral ciprofloxacin therapy of infection caused by multiply resistant bacteria other than Pseudomonas aeruginosa.

Of 125 patients treated with ciprofloxacin at the Columbia-Presbyterian Medical Center, New York, 34 had infections due to bacteria other than Pseudomonas aeruginosa. The mean age of the patients was 50 years (19-88 years) and most had significant underlying disease. There were nine lower respiratory infections, eight urinary tract infections, eight soft tissue infections, three osteomyelitis, and three intra-abdominal infections. The pathogens were: Escherichia coli, 7 (mean MIC 0.07 mg/l); Serratia marcescens, 6 (0.2 mg/l); Enterobacter spp., 5 (0.1 mg/l); Klebsiella pneumoniae, 3 (0.1 mg/l); Proteus mirabilis, 3 (0.06 mg/l); Cutrobacter freundii, 2 (0.06 mg/l), Staphylococcus aureus, 3 (0.5 mg/l); and one each of Acinetobacter anitratus. Haemophilus, influenzae, Salmonella enteritidis, Flavobacterium meningosepticum, and Streptococcus faecalis. Of these organisms 81% were resistant to ampicillin, 70% to carbenicillin, 22% to gentamicin, 49% to cefazolin and cephalexin, and 25% to cotrimoxazole. Ten patients had concomitant Ps. aeruginosa infections. Patients were treated orally with 500 mg or 750 mg ciprofloxacin every 12 h. The overall clinical response rate was 88%, and the bacteriological response 76%, and 65% if Ps. aeruginosa is included. Resistance to ciprofloxacin developed in one Staph. aureus and one Ser. marcescens (MIC greater than 2 mg/l). Toxicity was minor. Ciprofloxacin was effective and safe therapy of infections due to Gram-negative bacteria resistant to many of the currently available oral and parenteral agents.

Oral ciprofloxacin therapy of infections due to Pseudomonas aeruginosa.

The efficacy and safety of oral ciprofloxacin, a fluoroquinolone, were evaluated in the treatment of infection due to Pseudomonas aeruginosa. 96 infections in 71 patients were treated. Substantial underlying disease was present in most of the patients, and 25 (35%) were seriously ill. 52% of pseudomonas isolates were carbenicillin-resistant, and 31% gentamicin-resistant. The overall clinical response rate was 77%-28 of 35 exacerbations of cystic fibrosis respiratory disease, 17 of 19 urinary infections, 4 of 6 osteomyelitis, and 11 of 15 soft tissue infections. The bacteriological cure rate was 34%-0 of 35 cystic fibrosis, 4 of 17 respiratory infections, 17 of 19 urinary infections, 4 of 6 osteomyelitis, and 8 of 15 soft tissue infections. Ps aeruginosa developed resistance to ciprofloxacin in 25 of 96 infections. Side-effects were generally slight with nausea in 14 (15%) the most common, and there were only two substantial superinfections.

Ceftriaxone in the treatment of serious infections, particularly after surgery.

The clinical efficacy and safety of ceftriaxone when administered twice daily was evaluated in the treatment of serious infections, including 9 episodes of bacteremia, 4 of pneumonia, 7 of intra-abdominal or soft tissue infections, 11 of urinary tract infections, 3 of osteomyelitis, and 5 of meningitis. Causative pathogens were Strep. pneumoniae, other hemolytic streptococci, E. coli, P. mirabilis, K. pneumoniae, and species of Enterobacter, Serratia, and Pseudomonas. The overall clinical cure rate was 87 percent and the bacteriologic cure rate was 77 percent. Cures were achieved in infections due to organisms resistant to ampicillin, cefazolin, cefamandole, carbenicillin, and gentamicin. Peak plasma levels were far in excess of the minimal inhibitory concentrations of Enterobacteriaceae. Adverse effects were infrequent, and in only one instance was it necessary to discontinue treatment. Resistance to ceftriaxone developed during therapy with several Enterobacter and Pseudomonas species isolates. Ceftriaxone appears to be a useful agent for treatment of serious gram-negative infections in seriously ill patients.