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 ...

A multicenter, prospective randomized trial was conducted to determine if the addition of rifampin to a combination therapy of an antipseudomonal beta-lactam agent and aminoglycoside improves the outcome of patients with Pseudomonas aeruginosa bacteremia. The Zelen protocol for randomized-consent design was used. Consent was sought only from patients randomized to the experimental therapy (rifampin+). If the experimental therapy was refused, the patient would then receive the standard combination therapy (control); however, when outcome was evaluated, all patients randomized to the rifampin+ group, including those that declined rifampin, were compared with the control group. One hundred twenty-one consecutive hospitalized patients with positive blood cultures for P. aeruginosa were enrolled. Entry was stratified for prior use of empiric antipseudomonal antibiotics, neutropenia, severity of illness, and presence of pneumonia. Fifty-eight patients were randomized to receive rifampin (600 mg orally every 8 h for the first 72 h and then every 12 h for a total of 10 days) plus a beta-lactam agent plus an aminoglycoside. Sixty-three received the standard therapy of a beta-lactam plus an aminoglycoside agent (control). Bacteriologic cure occurred significantly more frequently in patients randomized to the rifampin+ regimen. Breakthrough or relapsing bacteremias occurred in 2% of the three-drug (rifampin+) group, compared with 14% for the two-drug (standard therapy) group. Despite this favorable trend in bacteriological response, no significant differences in survival were seen for the two treatment groups. Rifamycin derivatives warrant further clinical study as antipseudomonal agents. The Zelen protocol appears well suited for comparative trials of antimicrobial agents.Pseudomonas aernginosa continues to be an important pathogen, especially among debilitated and immunocompromised individuals. Infections caused by P. aeruginosa are difficult to treat because of the organism's intrinsic resistance to many antibiotics and its propensity to develop resistance during therapy (10,(13)(14)(15)(16)(17). These properties have so limited the effectiveness of antibiotic monotherapy that combination antibiotic therapy has been advocated for serious P. aeruginosa infection (1,11,13,19). Nevertheless, the mortality rates for bacteremia due to P. aeruginosa continue to be consistently higher than for other bacterial pathogens (1,3,5,8).In an exploration for more potent antipseudomonal combinations of antibiotics, rifampin was found to be synergistic in vitro with antipseudomonal penicillin and an aminoglycoside against P. aeruginosa (20,22,26). Compared with the double combination of an antipseudomonal beta-lactam agent and an aminoglycoside, a triple combination of rifampin, an antipseudomonal beta-lactam agent, and an aminoglycoside significantly improved survival in neutropenic mice infected with P. aeruginosa (9,21,25). Moreover, selected patients with P. aeruginosa sepsis who failed standard antipseudomonal combination therapy w...

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In this study we estimated occurrence of the booster effect in a population infected with the human immunodeficiency virus (HIV) and assessed the relation between the booster effect, T-lymphocyte CD4 cell counts, tuberculosis risk categories, and HIV exposure categories. Patients were recruited from 13 participating sites of the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). A two-stage tuberculin skin test was applied to 709 HIV-infected patients using the Mantoux method. An induration reading < 5 mm on the first test and > or = 5 on the second skin test defined the booster effect. Overall, 18 patients, or 2.7% (95% confidence interval, 1.6 to 4.2) experienced the booster effect. Boosted responses were seen in eight (2.1%) anergic patients, six (4.5%) nonanergic patients, and four (2.5%) with anergy status unknown. Boosting was noted in 1 of the 131 women enrolled. Age, race, CD4 cell count, injection drug use, anergy status, tuberculosis risk categories, and HIV exposure categories were not predictive of boosting. The booster effect occurs in a small percentage of HIV-infected patients tested, thus identifying small numbers of patients with latent tuberculosis infection. The two-stage procedure is probably of limited value in the diagnosis of latent tuberculosis in HIV-infected persons.