Penetration of topically applied ciprofloxacin, norfloxacin, and ofloxacin into the aqueous humor.

PURPOSE: To determine the intraocular penetration of topically applied fluoroquinolone antibiotics into aqueous humor. METHODS: Thirty-two patients undergoing cataract extraction received either 0.3% ciprofloxacin, 0.3% norfloxacin, or 0.3% ofloxacin topical drops. The patients were given two drops 90 minutes preoperatively and two drops 30 minutes preoperatively. At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber and immediately stored at -70 degrees C. RESULTS: Concentrations of ciprofloxacin, norfloxacin, and ofloxacin were determined using a broth dilution bioassay. Morganella morganii with a known minimal inhibitory concentration was used to assay ciprofloxacin and norfloxacin levels. Salmonella enteritidis with a known minimal inhibitory concentration was used to assay ofloxacin levels. Topically applied ciprofloxacin achieved a mean aqueous level of 0.072 microgram/ml (range, 0.02-0.153 microgram/ml). One sample was below the sensitivity of the bioassay. Topical norfloxacin achieved a mean aqueous level of 0.0570 microgram/ml (range, 0.046-0.10 microgram/ml). Seven samples did not reach the sensitivity of the bioassay. Topical ofloxacin achieved a mean level in the aqueous humor of 0.338 microgram/ml (range, 0.078-0.625 microgram/ml). There was no statistically significant difference in intraocular aqueous humor levels of ciprofloxacin versus norfloxacin (P > 0.05). Topical ofloxacin achieved aqueous humor levels significantly higher than either ciprofloxacin or norfloxacin (P < 0.004). CONCLUSION: Of the currently available topical fluoroquinolone antibiotics, ofloxacin achieves the highest aqueous humor concentrations.

Therapy of pulmonary nocardiosis in immunocompromised mice.

We compared the bactericidal efficacies of various antimicrobial agents and combinations thereof in experimentally induced Nocardia asteroides pneumonia in immunocompromised mice. Cortisone acetate treatment, which produced impaired cell-mediated immune function, was followed by nasal inoculation of 5 x 10(4) CFU of N. asteroides into each mouse. Therapy was begun 24 h after inoculation and continued for the next 96 h. Dosages of antimicrobial agents resulted in concentrations approximating levels in human serum. Animals from each of nine treatment groups were sacrificed every 24 h. The pulmonary tissue obtained was homogenized and quantitatively cultured. Results were calculated to indicate the number of CFU per gram of lung tissue. Amikacin and imipenem were the two most effective single agents studied. Sulfadiazine and ciprofloxacin were ineffective, and ceftriaxone reduced bacterial counts modestly. Combination therapy did not enhance the bactericidal activities of the agents tested. We conclude that amikacin and imipenem, as well as select broad-spectrum cephalosporins, represent therapy superior to the sulfonamides in this experimental model and may represent alternative treatment for patients who cannot tolerate sulfa agents (e.g., human immunodeficiency virus-infected patients) or who fail primary treatment.

Strategies for the management of varicella-susceptible healthcare workers after a known exposure.

Three different sequentially applied post-varicella zoster virus (VZV) exposure management strategies were employed over a 43-month period. We began by using a standard post-exposure protocol in which 50 susceptible healthcare workers (HCW) involved in hospital exposures were furloughed from work at a loss to the hospital of 424 workdays and $46,000. Of the eight nosocomial cases of VZV infection in HCWs, four (50%) caused future HCW and patient exposure. In trial I, we substituted a post-exposure screening procedure for the standard work furlough procedure. We screened 77 exposed staff resulting in one nosocomial VZV infection that was the source of another exposure incident. No secondary cases of varicella resulted from this exposure and only 20 days of furlough time were used during trial I. As VZV resulting from a home exposure source was responsible for most hospital exposures in which HCWs were the source, our trial II protocol added the Centers for Disease Control's (CDC) off-duty procedure, but limited its use to susceptibles exposed at home. The 43-month overall attack rate of nosocomial varicella was 4.7%, while the true home exposure attack rate was 79% (p less than .00001). There was an average of 42.4 lost workdays charged to the hospital per incident under the standard protocol and three days per incident in the combined experience of trials I and II (p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrobial synergism in the therapy of experimental cerebral nocardiosis.

A mouse model of cerebral nocardiosis was used to determine the efficacy of synergistic antimicrobial combinations in reducing bacterial colony counts per gram of brain tissue. The combinations of imipenem-cefotaxime and imipenem-trimethoprim/sulphamethoxazole (TMP/SMP) were compared with each other and with each agent used alone. A saline treated control group was also included. At the completion of 72 h of therapy the combinations of imipenem-cefotaxime and imipenem-TMP/SMX were the most effective in reducing bacterial colony counts. These were statistically superior to cefotaxime and TMP/SMX used alone but not statistically superior to imipenem alone. TMP/SMX was not effective in this model and was inferior to all other antibiotic treatments.

Susceptibility of Nocardia asteroides to new quinolones and beta-lactams.

The susceptibility of 31 strains of Nocardia asteroides to various quinolones and beta-lactams, as well as coumermycin, amikacin, and minocycline, was determined by the agar dilution technique. Ciprofloxacin was the most active fluoroquinolone tested on a weight basis, as it inhibited approximately 50% of the isolates at achievable drug levels in serum. Ceftriaxone and cefpirome were the most active cephalosporins in this system with MICs of 8 micrograms/ml for 80% of strains tested. Imipenem, amikacin, and minocycline were the most effective agents tested.

A comparative trial of clotrimazole troches and oral nystatin suspension in recipients of renal transplants. Use in prophylaxis of oropharyngeal candidiasis.

An open study designed to compare the effectiveness and safety of clotrimazole troches with nystatin oral suspension in the prevention of oropharyngeal candidiasis was conducted. This study was performed as the troche form of clotrimazole was easier to administer and less costly than nystatin oral suspension. Sixty assessable patients were randomized to receive either clotrimazole troches (n = 32) or nystatin oral suspension (n = 28) for a 60-day period after receiving a renal allograft. The two groups were comparable in age, sex, type of transplant, and amount of immunosuppression. Both regimens were 100% effective in preventing the development of thrush in the patients studied. Adverse effects were infrequently seen in either group (one case of mild nausea in the clotrimazole group and three cases in the nystatin group). One patient chose to withdraw from the clotrimazole group, and eight patients withdrew from the nystatin group before completing 60 days of therapy (P = .002). Reasons given for withdrawal were the unpleasant taste of the drugs, or an inability to comply with the protocol. The cost of clotrimazole troches in the prophylactic doses given in this study was approximately one tenth that of nystatin oral suspension. Clotrimazole troches are effective, less expensive, and easier to self-administer than nystatin oral suspension.

Therapy of experimental cerebral nocardiosis with imipenem, amikacin, trimethoprim-sulfamethoxazole, and minocycline.

A mouse model of cerebral nocardiosis was used to determine relative antibiotic efficacy by reducing bacterial colony counts per gram of brain tissue. The antimicrobial agents employed were demonstrated in vitro to be inhibitory to most strains of Nocardia asteroides at very low concentrations. The agents used in this study were imipenem-cilastatin, amikacin, trimethoprim-sulfamethoxazole, and minocycline. Antibiotics were administered every 4 h for 72 h before animal sacrifice. Bacterial colony counts were assayed at various time points before the completion of therapy. Imipenem-cilastatin and amikacin were the most effective agents tested. Trimethoprim-sulfamethoxazole was less effective than imipenem and amikacin but more effective than minocycline. Minocycline did not eradicate intracerebral organisms and was similar to saline (control) in its effects.

Susceptibility of Eikenella corrodens to newer and older quinolones.

The susceptibilities of 44 clinical strains and a reference strain (ATCC 23834) of Eikenella corrodens were determined by agar dilution. All isolates were very susceptible (MICs, less than 2 micrograms/ml) to amifloxacin, ciprofloxacin, difloxacin, enoxacin, norfloxacin, ofloxacin, and Win 35439.

Amikacin synergism with beta-lactam antibiotics against selected nosocomial pathogens.

The synergistic interaction between amikacin and several investigational antibiotics against seven different genera of nosocomial pathogens was assessed using the microtitre checkerboard technique. The greatest percentage of tests showing synergy was when amikacin was used in combination with apalcillin and azlocillin particularly against Serratia marcescens and Proteus spp. When amikacin was combined with several new semi-synthetic cephalosporins, synergy was present in a variable percentage of tests. No antagonism was found in any of the tested combinations.

Comparison of agar dilution, microtitre broth dilution and tube macrodilution susceptibility testing of ciprofloxacin against several pathogens at two different inocula.

The susceptibility of six different genera of organisms to ciprofloxacin was determined by the tube macrodilution, broth microdilution and the agar dilution methods. The minimal inhibitory concentrations of ciprofloxacin determined by the broth microdilution and the agar dilution methods correlated well with each other, but in general the tube macrodilution technique gave somewhat higher results. Raising the initial inoculum of the tested organisms from 1 X 10(5) to 1 X 10(7) cfu/ml did not result in a significant increase in the minimal inhibitory or bactericidal concentrations of ciprofloxacin.

The relationship between intravenous fluid contamination and the frequency of tubing replacement.

Medical patients receiving IV therapy were randomly assigned to one of two IV tubing change groups. One group had a 48-hour tubing change and the other had no tubing change for the remainder of the cannula placement. A daily IV fluid specimen was processed microbiologically. To complete the study, a minimum of 3 continuous days of therapy and three fluid specimens was required. There were two contaminated specimens, one in each tubing change group. The contamination rate in the 48-hour change group was 0.87% and 0.96% in the no change group. The rate difference of 0.09% has a 95% confidence interval (-0.035 to +0.036) which includes zero. Survival analysis also revealed no significant difference in the cumulative probability of survival, however the mean duration of continuous tubing use of 4.3 days in the no change group and 1.8 days in the 48 hour change group were significantly different (p less than 0.05). The cumulative probability of surviving contamination free was 0.988 in the 48-hour group and 0.987 in the no-change group. We conclude that it is safe to change IV tubing at intervals up to but not exceeding 4 days.

Cefoperazone therapy of complicated urinary tract infections: pharmacokinetics in renal transplant recipients.

Cefoperazone was used to treat patients with complicated urinary tract infections due to multiple antibiotic-resistant gram-negative rods who had failed prior courses of intravenous antibiotic therapy. Cure was achieved in 44% (4/9) of cases; 44% of patients improved but relapsed and 11% (1/9) of patients were reinfected. Relapse and reinfection were associated with Pseudomonas aeruginosa and/or with conditions not normally responsive to medical therapy alone including prostatitis, reflux and chronic indwelling Foley catheters. The pharmacokinetics of cefoperazone were studied in renal transplant recipients. Peak serum concentrations (range 146-241 micrograms/ml) and 2-hour noncumulative urine concentrations (range 161-291 micrograms/ml) exceeded the minimal inhibitory concentrations of the bacteria in all cases. There was no accumulation of cefoperazone despite the presence of impaired renal function.

Susceptibility of multiply antibiotic-resistant pneumococci to the new quinoline antibiotics, nalidixic acid, coumermycin, and novobiocin.

The susceptibility of 10 multiply antibiotic-resistant strains of Streptococcus pneumoniae to several quinoline antibiotics and to coumermycin, novobiocin, and penicillin was determined. The MIC of penicillin for all test isolates was greater than or equal to 4 micrograms/ml. Ciprofloxacin was the most active quinoline derivative tested, followed by norfloxacin. These isolates of S. pneumoniae were not inhibited by the remaining quinolines at achievable concentrations in serum. Coumermycin and ciprofloxacin were the most active antibiotics tested in this study.

Cefmenoxime therapy of serious bacterial infections.

The efficacy and safety of cefmenoxime was evaluated in 50 patients with serious bacterial infections. These included 26 pneumonias, 18 urinary tract infections, 2 soft tissue infections, 2 bacteremias, 1 renal abscess, and 1 peritonitis. A satisfactory clinical response was seen in 47 patients (94%). Eosinophilia and thrombocytosis were seen in several patients but were generally mild and transient.

Cavitary Legionnaires' pneumonia: nosocomial infection in renal transplant recipients.

Cavitation is an unusual manifestation of legionnaires' pneumonia. Mortality rates range from 24 to 58 percent with effective therapy. Antibiotic therapy is not standardized and is largely based on anecdotal reports. This report has described nosocomially acquired cavitary legionnaires' pneumonia in five renal transplant recipients. The diagnosis was made by seroconversion and immunofluorescent staining of lung tissue or transtracheal aspirates. Frequently seen associated symptoms were not present. All patients were successfully treated with 2 to 4 g of erythromycin for at least 4 weeks.

Synergism of imipenem and amikacin in combination with other antibiotics against Nocardia asteroides.

The in vitro activities of imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK0787) and amikacin in combination with cefotaxime, trimethoprim-sulfamethoxazole, and each other were tested against 26 Nocardia asteroides strains. The agar dilution method was used for all tests. Synergy was present in 80% of tests with imipenem-trimethoprim-sulfamethoxazole, in 92% of tests with imipenem-cefotaxime, and in 83% of tests with amikacin-trimethoprim-sulfamethoxazole. Indifference was found on rare occasions, and no antagonism was seen.

Adult respiratory distress syndrome as a cause of death in pneumococcal pneumonia. Report of ten cases.

The Pneumococcus continues to be a common cause of infectious pneumonia; however, the cause of death in pneumococcal disease remains obscure. Ten patients are described who developed the adult respiratory distress syndrome (ARDS) secondary to pneumococcal pneumonia. The patients are young (median age, 33 years) and leukopenic (median white blood cell count, 2.1 cells/cu mm) and have a mortality of 50 percent (five patients). It is postulated that pulmonary sequestration of leukocytes may play a role in the pathogenesis of ARDS secondary to pneumococcal disease. Four different pneumococcal capsular subtypes (9V [68]; 9A [33]; 4; 3) were found capable of causing ARDS. The currently available pneumococcal vaccine does not contain two of the capsular subtypes associated with ARDS.