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Combination antimicrobial agent therapy has been advocated for treatment of gram-negative bacteremia, including that caused by KlebsielUa spp. We performed a prospective, observational, 10-hospital collaborative study to evaluate the efficacy of antibiotic combination therapy versus that of monotherapy for 230 consecutive patients with KiebsieUla bacteremia. The species involved were K. pneumoniae (82%), K. oxytoca (15%), and K. ozaenae (0.4%). Of the bacteremias, 26% were polymicrobial in nature. A total of 53% of cases were nosocomial infections. The most common portals were the urinary tract (28%), biliary tract (12%), lung (10%b), and abdomen (9%k). Some 49 and 51% of the patients had received monotherapy and antibiotic combination therapy (beta-lactam plus aminoglycoside), respectively; 14-day mortalities in the two groups were 20 and 18%, respectively. However, for the subgroup of patients who experienced hypotension within 72 h prior to or on the day of the positive blood culture, those patients who received combination therapy experienced significantly lower mortality (24%) than did those who received monotherapy (50%k). We conclude that monotherapy with an antibiotic that is active in vitro against KiebsieUla (beta-lactam or aminoglycoside) is sufficient therapy for less severely ill patients (immunocompetent, urinary tract portal, mentally alert, normal vital signs). On the other hand, for severel ill patients who experience hypotension, antibiotic combination therapy with a beta-lactam and an aminoglycoside agent is preferred.Klebsiella spp. are the second most frequent cause of gram-negative bacteremia (3,5,12,14). Combination therapy with a beta-lactam and an aminoglycoside has been advocated for treatment of Klebsiella bacteremia because of its notable mortality (1,11,15).Most studies of bacteremia have focused on Klebsiella spp. not as a single entity but, rather, have included it in the category of gram-negative bacteremias. This is problematic, given the inherent differences in antibiotic susceptibility and virulence among the aerobic gram-negative rods. Young (15) has also pointed out that failure to stratify patients by underlying disease category in most studies of therapy for gram-negative bacteremia has resulted in invalid comparisons of antibiotic efficacy.We performed a prospective, observational, multicenter collaborative study to evaluate the efficacy of antibiotic combination therapy versus monotherapy on the outcome of Klebsiella infections. We made a concerted effort to address those areas of weakness that have characterized previous studies, including a prospective rather than retrospective study design, adequate sample size for statistical evaluation, assessment for severity of illness, and requirement for bacteremia as an eligibility criterion. Furthermore, given the large sample size of 230 patients, analysis by subgroups including underlying disease was feasible. MATERIALS AND METHODSStudy design. From 1986 to 1987, 230 consecutive patients from whose blood Klebsiella spp. were ...

One gram of ceftriaxone was given intravenously to 15 patients approximately 2 h before cardiopulmonary bypass surgery. Ceftriaxone levels in plasma (mean ± standard deviation) were 60.4 ± 18.8 ,ug/ml (range, 17.0 to 96.0 ,ug/ml) at the beginning of bypass, 44.2 ± 16.6 ,ug/ml (range, 9.4 to 78.6 ,ug/ml) at the end of bypass, and 19.6 ± 9.6 ,ug/ml (range, 4.2 to 47.1 ,ug/ml) the following morning, 18.1 to 24.7 h after infusion of ceftriaxone. Concentrations in the sternal bone were 4.7 ± 2.1 ,xg/g (range, 1.0 to 10.1 ,ug/g; tissue-toplasma ratios, 0.066 ± 0.036). Concentrations in the atrial appendage were 7.7 ± 1.8 ,ug/g (range, 3.6 to 10.2 ,ug/g; tissue-to-plasma ratios, 0.143 ± 0.062). These data suggest that a single dose of ceftriaxone might be useful for prevention of infection due to susceptible pathogens.Cephalosporins are widely used for prevention of infection in patients undergoing cardiac surgery. However, microorganisms resistant to older cephalosporins such as cephalothin, cefazolin, and cefamandole sometimes cause postoperative infections in these patients (1,8,10). Bor et al. (1) reported that 13 gram-negative isolates from cases of mediastinitis after cardiac surgery were resistant to antimicrobial agents used perioperatively. Thus, newer cephalosporins may find a place in such preventive therapy.Ceftriaxone is a new cephalosporin with a broad spectrum of activity against both gram-positive and gram-negative microorganisms. Various investigators have determined that 90% of strains of most members of the family Enterobacteriaceae are inhibited by ceftriaxone concentrations of 1 ,ug/ml (5-7) and that 90% of Staphylococcus aureus strains are inhibited by concentrations of 3.1 to 4 ,ug/ml (5, 7). The elimination half-life of ceftriaxone in normal volunteers, ranging from 6 to 8.6 h (6, 9), exceeds that of all cephalosporins studied to date. We determined levels of ceftriaxone in plasma and tissue after a single intravenous dose to patients undergoing cardiopulmonary bypass surgery. MATERIALS AND METHODSA total of 15 patients (14 men, 1 woman) scheduled for elective saphenous vein bypass grafting for coronary artery disease were given 1 g of ceftriaxone before the procedure. The patients were 49 to 68 years of age (mean ± standard deviation, 55.6 ± 8.4), weighed 53.8 to 121.8 kg (83.8 ± 13.7), and had normal renal function and no recent history of infection or antimicrobial therapy. The protocol was approved by the institutional review boards. Patients received ceftriaxone by intravenous infusion over 20 to 30 min approximately 1 h before the anticipated skin incision and 2 h before the anticipated bypass procedure. This single dose was the only perioperative antimicrobial therapy administered to these patients.Blood samples were collected in heparinized tubes. The first sample was obtained 20 to 50 min after completion of the infusion. At the time of median sternotomy, a portion of the xiphoid process was removed for determination of * Corresponding author.antibiotic concentration, and a second blood...

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