Comparison of difloxacin, enoxacin, and cefazolin for the treatment of experimental Staphylococcus aureus endocarditis.

This study compared difloxacin administered orally, enoxacin administered orally, and cefazolin administered intramuscularly for the treatment of experimental Staphylococcus aureus endocarditis. Difloxacin significantly reduced bacterial counts of vegetations compared with enoxacin. This study demonstrated that difloxacin was significantly more effective than enoxacin and as effective as cefazolin for the treatment of S. aureus endocarditis in rabbits.

Comparison of difloxacin, enoxacin, and cefoperazone for treatment of experimental Enterobacter aerogenes endocarditis.

This study compared difloxacin administered orally, enoxacin administered orally, and cefoperazone administered intramuscularly for the treatment of experimental Enterobacter aerogenes endocarditis. Difloxacin significantly reduced bacterial counts of vegetations, as compared with enoxacin and cefoperazone. Enoxacin and cefoperazone did not differ significantly. This study demonstrated that difloxacin was significantly more effective than enoxacin and cefoperazone for the treatment of E. aerogenes endocarditis in rabbits.

Therapy vs no therapy for bacteriuria in elderly ambulatory nonhospitalized women.

This prospective randomized study was undertaken to determine the efficacy of antimicrobial therapy compared with no therapy for bacteriuria in elderly ambulatory nonhospitalized women. Sixty-one women (mean age, 85.8 years) with bacteriuria were in the no therapy control group and 63 women (mean age, 85.8 years) with bacteriuria were in the therapy group; none had symptoms of urinary tract infection. One short course of antimicrobial therapy achieved a cure rate of 68.3% (43 of 63 women cured) two weeks after treatment. During the six-month follow-up period, ten (16.4%) of 61 women in the no therapy group and five (7.9%) of 63 women in the therapy group developed symptomatic urinary tract infection. At the time of six-month follow-up, 19 (34.5%) of 55 women in the no therapy group and 35 (63.6%) of 55 women in the therapy group did not have bacteriuria. We conclude that for asymptomatic bacteriuria in elderly ambulatory nonhospitalized women, short-course antimicrobial therapy is effective at two-week follow-up and that antimicrobial therapy can eliminate bacteriuria in most of these women for at least a six-month period.

Lack of association between bacteriuria and symptoms in the elderly.

In a study of bacteriuria in elderly (mean age 85 years, range 69 to 101), mostly middle- and upper-class Jewish subjects, attempts were made to determine if bacteriuria without dysuria is otherwise asymptomatic. Seventy-two subjects (59 women and 13 men) without dysuria were questioned about other urinary symptoms (incontinence, frequency, urgency, suprapubic pain, flank pain, fever) and symptoms indicating a lack of well-being (anorexia, difficulty in falling asleep, difficulty in staying asleep, fatigue, malaise, weakness) when they were with and without bacteriuria. Twenty-two subjects had bacteriuria that resolved spontaneously; bacteriuria subsequently developed in 24 nonbacteriuric subjects; and 26 subjects had bacteriuria that resolved with antimicrobial therapy. Subjects occasionally reported urinary symptoms (especially incontinence) and commonly reported symptoms indicating a lack of well-being when they were with and/or without bacteriuria. However, no differences in symptoms were found when bacteriuric subjects were compared with themselves when they were nonbacteriuric. Thus, bacteriuria without dysuria in the elderly appears to be asymptomatic.

Teicoplanin compared with vancomycin for treatment of experimental endocarditis due to methicillin-resistant Staphylococcus epidermidis.

This study compared teicoplanin with vancomycin without and with gentamicin and/or rifampin for treatment of experimental endocarditis due to methicillin-resistant Staphylococcus epidermidis. In rabbits treated for three days and killed 12 hr after the last doses of antimicrobial agents, no significant difference in reducing bacterial titers of vegetations was detected between vancomycin and teicoplanin without and with gentamicin and/or rifampin. Addition of gentamicin and/or rifampin to vancomycin or teicoplanin significantly reduced bacterial titers of vegetations compared with vancomycin or teicoplanin alone. Addition of rifampin alone or gentamicin plus rifampin was significantly more effective than addition of gentamicin alone. In rabbits treated for three days and killed seven days after the last doses of antimicrobial agents, no significant difference in sterilizing vegetations was detected between vancomycin and teicoplanin with gentamicin and/or rifampin. However, there was a trend (probably due to the longer elimination half-life of teicoplanin in serum) that clearly favored teicoplanin over vancomycin. Teicoplanin plus rifampin without or with gentamicin is at least as effective as vancomycin plus rifampin without or with gentamicin for treatment of experimental endocarditis due to methicillin-resistant S. epidermidis.

Enoxacin compared with vancomycin for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis.

Enoxacin administered orally was compared with vancomycin administered intravenously for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis. The MICs and MBCs of both enoxacin and vancomycin for an inoculum of 5.0 X 10(5) CFU of the methicillin-resistant S. aureus strain per ml were 1.56 microgram/ml. With an inoculum of 10(8) CFU/ml, enoxacin at 6 micrograms/ml and vancomycin at 180 micrograms/ml resulted in similar decreases in numbers of methicillin-resistant S. aureus in broth. Methicillin-resistant S. aureus endocarditis in rabbits was treated with enoxacin at 100 mg/kg orally every 12 h or vancomycin at 30 mg/kg intravenously every 12 h for 3 or 5 days. Enoxacin treatment for 3 or 5 days and vancomycin treatment for 5 days significantly reduced bacterial counts of vegetations compared with those in untreated control rabbits after 1 day of infection. Bacterial counts of vegetations after vancomycin treatment for 3 days did not differ significantly from those of untreated controls. Bacterial counts of vegetations in the four therapeutic groups did not differ significantly from one another. In uninfected rabbits single doses of vancomycin at 30 mg/kg administered intravenously achieved much higher concentrations in serum than did single doses of enoxacin at 100 mg/kg administered orally. Enoxacin had an elimination half-life in serum that was approximately 1.5 times longer than that of vancomycin. This study demonstrated that enoxacin administered orally is as effective as vancomycin administered intravenously for the treatment of experimental methicillin-resistant S. aureus endocarditis.

Epidemiology of bacteriuria in an elderly ambulatory population.

This study of bacteriuria in elderly (mean age 85 years, range 68 to 103) Jewish subjects of mostly middle and upper class attempted to determine disease prevalence, define the turnover in infected subjects, and assess the relation between functional status and infection. The prevalence of bacteriuria (midstream clean-catch method) was assessed in 373 women and 150 men. It was higher in women (18.2 percent) than in men (6.0 percent) (p less than 0.001) and was more common in functionally impaired nursing home residents (23.5 percent) than in apartment house dwellers (12.1 percent) (p less than 0.01). In longitudinal studies, 260 subjects (184 women and 76 men) had three urine culture surveys at six-month intervals. The cumulative percent infected on at least one survey was high (women 30.4 percent, men 10.5 percent). However, persistence of the same organism on all three surveys was surprisingly infrequent (women 6.0 percent, men 1.3 percent), and the turnover of infected and noninfected subjects was considerable. Persistence of bacteriuria on all three surveys was significantly more common in nursing home residents (13.9 percent) than in apartment house dwellers (3.1 percent) (p less than 0.01). Thus, bacteriuria is common in the elderly and appears related to functional status. However, the turnover of infected and noninfected subjects was high, and surprisingly, persistence was not found in most. The transient nature of bacteriuria in most provides support against the treatment of asymptomatic bacteriuria in the elderly.

Enoxacin compared with cefoperazone for the treatment of experimental Enterobacter aerogenes endocarditis.

This study compared enoxacin administered orally with cefoperazone administered intramuscularly for the treatment of Enterobacter aerogenes endocarditis in rabbits. The MICs and MBCs of both enoxacin and cefoperazone for an inoculum of 10(5) CFU/ml of the E. aerogenes strain used were 0.8 micrograms/ml, respectively. With an inoculum of 10(8) organisms per ml, enoxacin at 2 and 5 micrograms/ml and cefoperazone at 60 and 155 micrograms/ml were effective in reducing titers of E. aerogenes in broth. E. aerogenes endocarditis in rabbits was treated with enoxacin (100 or 25 mg/kg orally every 6 h) or cefoperazone (60 mg/kg intramuscularly every 6 h) for 5 or 10 days. Enoxacin at 100 and 25 mg/kg significantly reduced bacterial titers of vegetations compared with those of untreated controls. Enoxacin at 100 mg/kg was significantly more effective than enoxacin at 25 mg/kg and cefoperazone. Enoxacin at 25 mg/kg and cefoperazone did not differ significantly. Cefoperazone and controls did not differ significantly. In uninfected rabbits single doses of cefoperazone achieved much higher concentrations in serum than single doses of enoxacin (25 and 100 mg/kg). The half-lives of enoxacin at 25 and 100 mg/kg were approximately three times longer than that of cefoperazone.

Mezlocillin and ticarcillin alone and combined with gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis.

The efficacies of mezlocillin and ticarcillin, each alone and in combination with gentamicin, in the therapy of experimental left-sided Enterobacter aerogenes endocarditis in rabbits were compared. Each beta-lactam was administered intramuscularly at a dose of 180 mg/kg every 6 h either alone or with gentamicin (1.7 mg/kg intramuscularly every 8 h). Bacterial populations at the start of therapy (7 days after initiation of infection) were 9 to 10 log10 CFU/g of vegetation. Ticarcillin produced concentrations in serum that were twice those produced by mezlocillin, but the therapeutic ratios of mezlocillin and ticarcillin (ratio of peak level in serum to MBC) were the same. All of the therapeutic regimens given for either 5 or 10 days were effective in reducing vegetation counts when compared with the untreated controls (P less than 0.01 for all comparisons), except mezlocillin alone and ticarcillin alone, which caused insignificant reductions in counts after 5 days of therapy (P greater than 0.05). After 10 days of therapy, the only regimen that was significantly different from another was that of mezlocillin plus gentamicin, which was significantly better than that of ticarcillin alone (P less than 0.01). These studies document that mezlocillin and ticarcillin were both effective in reducing the numbers of E. aerogenes CFU in vegetations in rabbits with experimental endocarditis when the drugs were given over a prolonged course. More rapid and extensive reduction in vegetation counts was achieved with combinations of an aminoglycoside plus mezlocillin or ticarcillin. Mortality was significantly less among rabbits treated with mezlocillin plus gentamicin.

Pharmacokinetics of cefoperazone in normal subjects and patients with hepatosplenic schistosomiasis.

The pharmacokinetics of cefoperazone were studied and compared in four normal subjects and six patients with hepatosplenic schistosomiasis (HSS) with mild liver disease but marked portal hypertension. All subjects received a 2 g intravenous infusion of cefoperazone over 15 min. Although most pharmacokinetic parameters did not differ significantly between normal subjects and patients with HSS, the serum beta half-life of cefoperazone was longer in patients with HSS compared to normal subjects (3.0 h vs. 1.7 h). This demonstrates only mild impairment of excretion of cefoperazone in patients with HSS.

Aztreonam, cefoperazone, and gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis in rabbits.

The effectiveness of aztreonam, cefoperazone, and gentamicin alone and in combination was evaluated in Enterobacter aerogenes endocarditis in rabbits. The minimal inhibitory concentration/minimal bactericidal concentration ratios for E. aerogenes were as follows: aztreonam, 0.4/0.4 microgram/ml; cefoperazone, 0.8/0.8 microgram/ml; and gentamicin, 3.1/3.1 micrograms/ml. With an inoculum of 10(9) organisms per ml, aztreonam and cefoperazone were equivalent in reducing titers of E. aerogenes in broth, and both drugs demonstrated an increased rate of reduction when gentamicin was added; gentamicin alone was least effective. E. aerogenes endocarditis in rabbits was treated intramuscularly with aztreonam (60 mg/kg) every 6 h, with cefoperazone (60 mg/kg) every 6 h, with gentamicin (1.7 mg/kg) every 8 h, and with aztreonam plus gentamicin or cefoperazone plus gentamicin for 5 and 10 days, respectively. All of the therapeutic regimens were effective in reducing vegetation titers as compared with untreated controls. Aztreonam plus gentamicin was more effective than either aztreonam or gentamicin alone. Cefoperazone plus gentamicin was more effective than cefoperazone alone but was not more effective than gentamicin alone. Neither aztreonam and cefoperazone nor aztreonam and gentamicin differed significantly, but gentamicin was significantly more effective than cefoperazone. Aztreonam plus gentamicin did not differ significantly in effectiveness from cefoperazone plus gentamicin. Aztreonam gave a peak level of about 135 micrograms/ml and a half-life of 0.7 h. Cefoperazone gave a peak level of about 155 micrograms/ml and a half-life of 1.1 h. Gentamicin gave a peak level of 7.4 micrograms/ml and a half-life of 1.3 h.

Therapy for experimental endocarditis due to Staphylococcus epidermidis.

Vancomycin was evaluated with and without gentamicin and/or rifampin in therapy for endocarditis due to methicillin-resistant Staphylococcus epidermidis in rabbits. Vancomycin (30 mg/kg iv every 12 hr), gentamicin (3.5 mg/kg im every 8 hr), rifampin (20 mg/kg im every 12 hr), combinations of vancomycin plus gentamicin, vancomycin plus rifampin, and vancomycin plus gentamicin plus rifampin were injected for two days, and the number of bacteria in vegetations was determined. Ratios of minimal inhibitory concentrations to minimal bactericidal concentrations (microgram/ml) for S. epidermidis were 3.1:25 for vancomycin, 0.2:0.8 for gentamicin, and 0.4:0.4 for rifampin. After two days of therapy, mean log colony-forming units +/- SD in vegetations were 7.1 +/- 1.5 (none of eight animals were sterile) for vancomycin; 4.6 +/- 2.2 (two of nine) for gentamicin; 4.5 +/- 2.2 (two of eight) for rifampin; 3.3 +/- 1.3 (three of 10) for vancomycin plus gentamicin; 2.7 +/- 1.2 (three of nine) for vancomycin plus rifampin; 2.1 +/- 0.2 (eight of nine) for vancomycin plus gentamicin plus rifampin; and 8.1 +/- 1.3 (none of 12) for the control group. Gentamicin, rifampin, vancomycin plus gentamicin, and vancomycin plus rifampin were significantly more effective than was vancomycin; vancomycin plus rifampin was more effective than was gentamicin alone; and the combination of vancomycin plus gentamicin plus rifampin was more effective than were the drugs administered alone or in the combinations vancomycin plus gentamicin and vancomycin plus rifampin. Two days of treatment followed by seven days of no treatment resulted in 71%, 29%, and 14% sterile vegetations in rabbits receiving the combination therapy vancomycin plus gentamicin plus rifampin, vancomycin plus rifampin, and vancomycin plus gentamicin, respectively.

Cefoperazone pharmacokinetics in normal subjects and patients with cirrhosis.

The pharmacokinetics of cefoperazone were studied and compared in six normal subjects and six patients with severe liver disease. All subjects received a 2-g intravenous infusion of cefoperazone over 15 min. Significantly different results were noted between normal subjects and patients with cirrhosis (range [mean]) for the following: peak serum concentrations (203 to 345 [239] versus 82 to 206 [141] micrograms/ml; P less than 0.01); serum beta half-lives (1.0 to 1.8 [1.5] versus 2.3 to 9.9 [4.5] h; P less than 0.05); renal excretion (17 to 27 [21] versus 32 to 60 [50]%; P less than 0.01); and apparent volumes of distribution at steady state (4.1 to 7.8 [6.3] versus 12.7 to 23.8 [15.9] liters/1.73 m2; P less than 0.01). Lower peak serum levels in the patients with cirrhosis were probably related to an increased apparent volume of distribution secondary to ascites and to decreased serum protein binding of cefoperazone. Longer beta half-lives in the patients with cirrhosis were probably secondary to both decreased hepatic excretion caused by severe liver disease and to increased apparent volume of distribution. However, the longest beta half-life among the patients with cirrhosis was in a subject with a serum creatinine level of 2.1 mg/dl. We conclude that, although mild to moderate impairment of cefoperazone excretion occurs in patients with hepatic disease, adjustment of dosage may be necessary only with concomitant renal insufficiency.

Effect of cimetidine and antacid on gastric microbial flora.

The effect of a standard regimen of cimetidine on the gastric flora of 20 male volunteers was studied in a double-blind manner and compared with the effects of a standard antacid regimen. Postprandial microbial titers in gastric aspirates were significantly higher at 4, 8, and 16 weeks of therapy in subjects taking antacids and at 4 weeks in subjects taking cimetidine when compared with their pretreatment titers. Although not significant, there was a tendency for fasting microbial titers to be higher in subjects receiving cimetidine as compared with pretreatment titers. The higher titers were primarily related to increases in survival of mouth flora (viridans streptococci and Neisseria spp.); Enterobacteriaceae and other nitrate-reducing organisms were unusual isolates. There was no significant difference in the total titers or types of organisms isolated when subjects taking cimetidine were compared with those taking antacid.

Cefoperazone treatment of experimental endocarditis.

Cefoperazone (10 mg/kg) and cephalothin (20 mg/kg) administered intramuscularly every 6 h were both effective in reducing the number of Staphylococcus aureus cells in vegetations in rabbits with endocarditis. Cefoperazone produced higher peak concentrations and greater bactericidal activity in serum than did cephalothin. Cefoperazone (40 mg/kg) administered every 6 h was significantly more effective than cefamandole (40 mg/kg) administered every 6 h in reducing the number of Enterobacter aerogenes cells in vegetations. Although cefamandole produced higher peak concentrations in serum, the serum bactericidal activity was greater with cefoperazone. The half-lives in serum were 0.64 h for cefoperazone and 0.46 h for cephalothin and cefamandole.

Comparison of ceforanide, cefazolin, methicillin, and nafcillin in Staphylococcus aureus endocarditis therapy in rabbits.

Ceforanide (30 mg/kg) administered every 12 h, cefazolin (20 mg/kg) administered every 8 h and methicillin or nafcillin (40 mg/kg) administered every 6 h were equally effective in reducing the number of Staphylococcus aureus in vegetations in rabbits with endocarditis. These treatments were more effective than methicillin or nafcillin administered every 12 h. Ceforanide produced higher peak concentrations and greater bactericidal activity in serum than the other drugs and had the longest half-life (5.8 h, compared with 0.4 to 0.8 h for the other agents.

Effectiveness of nafcillin, methicillin, and cephalothin in experimental Staphylococcus aureus endocarditis.

Nafcillin, methicillin, and cephalothin (40 mg/kg every 6 h) were all effective in reducing the number of Staphylococcus aureus in vegetations in rabbits with endocarditis. Nafcillin and methicillin reduced the number of S. aureus at a significantly faster rate than did cephalothin. Nafcillin and methicillin also reduced titers of the S. aureus more rapidly than did cephalothin in vitro, both in broth and in rabbit serum.

Treatment of experimental Staphylococcus aureus abscesses: comparison of cefazolin, cephalothin, cefoxitin, and cefamandole.

Cefazolin (CZ), cephalothin (CF), cefoxitin (CX), and cefamandole (CM) were evaluated in therapy of Staphylococcus aureus infection produced in perforated table tennis balls placed intraperitoneally in rabbits. Four weeks after placement of two balls in each rabbit, a beta-lactamase producing strain of S. aureus was injected into one of the balls. Twenty-four hours later therapy was initiated with 40 mg of CZ or 80 mg of CF, CX, or CM per kg intramuscularly every 6 h. After 24 h of treatment, the mean log(10) colony-forming units per ml were 7.1 for CZ, 6.7 for CF, 6.5 for CX, and 7.2 for CM. After 72 h the mean log(10) colony-forming units per ml were 5.0 for CZ, 4.1 for CF, 3.6 for CX, and 5.6 for CM. After 8 days, the titers were 1.6/ml for CZ, 1.0 for CF, 1.9 for CX, and 3.6 for CM. CZ serum levels were about double CF and CX levels and about two-thirds of CM levels. In sterile ball fluid CZ and CM levels were more than double CF or CX concentrations. Concentrations of all four antibiotics were lower in infected balls.

Comparison of methicillin, nafcillin, and oxacillin in therapy of Staphylococcus aureus endocarditis in rabbits.

Methicillin (M), nafcillin (N), and oxacillin (OX) (400 mg administered intramuscularly every 8 hours) were compared in the therapy of left-sided endocarditis in rabbits infected with two different strains of Staphylococcus aureus. The three antibiotics were equally effective in eliminating staphylococci from cardiac vegetations. N and OX were four to eight times as active against the staphylococci as M in broth but had equivalent activity in serum. The peak M and OX levels in serum were at least twice the peak N level, but the half-life of N in the serum (2.1 hours) was about three times that of M (0.6 hours) and twice that of OX (1.1 hours). Serum bactericidal activity tests demonstrated essentially equal activity with the three antibiotics 1 and 2 hours after injection; however, at 4 and 6 hours N had an advantage over M and OX. Therefore, despite clear differences in vitro activity, protein binding, and pharmacodynamics, M, N, and OX were equally effective in therapy of staphylcoccal endocarditis in rabbits.