Recurrent gram-negative bacteremia: incidence and clinical patterns.

Fifty-eight patients who had at least two episodes of gram-negative bacteremia were evaluated to define the epidemiology of recurrent bacteremia caused by these organisms. Thirty-two patients (55%) had single relapses, 16 (28%) had one reinfection, and 10 (17%) had more than one recurrence of bacteremia. Intravenous catheters were the most common probable source of bacteremia. Relapses occurred earlier after the initial episode than did reinfections (58 days vs. 292 days; P = .002). The duration of antibiotic therapy for the first episode was shorter for patients with relapses than for those with reinfections (13.9 days vs. 17.5 days; P = .046). Microorganisms causing recurrent bacteremic episodes were not unusually resistant to antimicrobial agents. Reinfections may be difficult to prevent because they are associated with the severity of the underlying illness, which may not improve. The frequency of relapses might be reduced by increasing the duration of antibiotic therapy and eliminating foci of infection.     

Amikacin therapy of gram-negative bacteremia

Treatment with amikacin was evaluated in 15 patients with gram-negative bacteremia. The sources of sepsis were urinary tract (in six patients), abdomen (in five) and miscellaneous sites (in four). Sixteen bacterial pathogens were recovered, including three gentamicin-resistant organisms. All isolates were susceptible to amikacin. Eleven of the 14 patients who could be evaluated fulfilled the criteria for cure, including the three patients with gentamicin-resistant organisms. Three patients failed to respond to amikacin therapy. Monitoring untoward effects revealed eighth nerve toxicity in one patient and nephrotoxicity in one patient. These results indicate that amikacin is effective in the treatment of patients with gram-negative bacteremia, even when caused by gentamicin-resistant bacteria.     

Improved mortality in gram-negative bacillary bacteremia

From 1979 to 1982, the four years of this study, episodes of gram-negative bacillary bacteremia occurred in a 489-bed community teaching hospital--an increase of 15.9%. Mortality related to bacteremia was 19.4% overall and only 3.2% for the 158 episodes involving nonfatal underlying illnesses, lower figures than those reported in the past. The severity of underlying illnesses in bacteremic patients dominated all other clinical variables that were studied as prognostic factors for the outcome of the episode. The same bacteremia-related mortality was seen in patients who had empirically received (1) multiple-antibiotic regimens in which one or more drugs were active against the pathogenic organism(s), (2) either an appropriate aminoglycoside or beta-lactam antibiotic alone, or (3) both an aminoglycoside antibiotic and a beta-lactam antibiotic active against the pathogenic organism(s).     

Antibiotic therapy for gram-negative bacteremia.

Although antibiotic therapy is the mainstay of therapy for gram-negative bacillary bacteremia, the amelioration of the underlying conditions, the correction of predisposing factors, the drainage of abscesses, the removal of infected foreign bodies, and adequate supportive care are also of paramount importance for curing the infection and should not be neglected. Beginning in the late 1960s, most of the clinical work on gram-negative infections has focused on the evaluation of new antibiotics. Numerous studies have shown that early, appropriate antibiotic treatment of gram-negative bacteremia significantly improved patients' outcomes and prevented the development of septic shock. Prescribing standard doses of antibiotics does not necessarily mean that therapeutic levels will be reached in all patients, and relapses of infections or breakthrough bacteremias can occur in patients with subinhibitory serum levels of antibiotics. The monitoring of serum concentrations of antibiotic is therefore recommended in critically ill septic patients. Whereas initial studies on the antibiotic treatment of gram-negative bacteremia were carried out in nonneutropenic patients, more recent clinical investigations have been performed almost exclusively in cancer patients with neutropenia. Studies conducted in the 1970s and 1980s among these patients have shown the following: (1) early empirical therapy reduced the mortality of gram-negative bacteremia; (2) therapy with a combination of two antibiotics, be it an extended spectrum penicillin plus an aminoglycoside or a third-generation cephalosporin, has significantly improved patients' outcomes; and (3) triple-drug combinations (i.e., a penicillin plus a cephalosporin plus an aminoglycoside) are not superior to combinations of beta-lactams and aminoglycosides. For the treatment of gram-negative bacteremia, clinicians today have a choice between well-established antibiotic combinations and broad-spectrum single-agent therapy with third-generation cephalosporins or carbapenem antibiotics. Although recent studies suggested that monotherapy could be as effective as combination therapy for the empirical treatment of fever in the neutropenic host, no definitive study has so far unquestionably demonstrated the equivalence of these treatments in patients with gram-negative bacteremias, especially those caused by P. aeruginosa, or in patients with adverse prognostic conditions, such as persistent and profound granulocytopenia. This literature should however be reviewed with great caution. Indeed, only a minority of studies have included a sufficient number of patients to confidently assess the impact of therapy on patients' outcomes. Obviously, small studies can have a significant risk of type II errors, that is, making false-negative conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Molecular epidemiology of gram-negative bacteremia.

We did pulsed field gel electrophoresis (PFGE) and antibiotic susceptibility testing on 202 gram-negative isolates obtained from blood cultures between 1 January 1989 and 31 December 1993. Seventy-eight patients had at least two gram-negative isolates of the same species recovered from blood drawn one or more days apart and met the other study criteria. Twenty patients had only 1 bloodstream infection, 48 patients had 1 recurrence of bacteremia, and 10 patients had > 1 recurrence of bacteremia. Of 80 recurrences of bacteremia, 52 (65%) were relapses and 28 (35%) were reinfections. Seventy-eight percent of the episodes of bacteremia occurring < or = 300 days apart were relapses, and 100% occurring > 300 days apart were reinfections (P < .001). Organisms causing recurrent bacteremia were not more resistant than those causing initial episodes. In conclusion, most episodes of recurrent gram-negative bacteremia were relapses. Relapses and reinfections could not be distinguished only by the length of time between episodes or by antimicrobial susceptibility patterns.     

Principles of antibiotic treatment of gram-negative bacteremia

Summary Patients with gram-negative bacteremia studied between 1951–1958 (173 patients) and 1965–1974 (612 patients) were carefully evaluated to delineate critical determinants of outcome. Severity of the host's underlying disease was the major factor influencing outcome in both series. Early appropriate antibiotic therapy was associated with significant reductions in both fatality rates and the frequency of development of shock. Appropriate antibiotic therapy was also associated with a significant reduction in fatality rates even if initiated after the onset of shock. Most individual antimicrobial agents appeared to be of comparable efficacy provided the infecting organism was susceptible. Combinations of antibiotics could not be demonstrated to be more effective than single agents.

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Prinzipien der Antibiotikabehandlung der gramnegativen Bakteriämie

Zusammenfassung Patienten mit gramnegativer Bakteriämie, die zwischen 1951–1958 (173 Patienten) und 1965–1974 (612 Patienten) untersucht wurden, wurden sorgfältig auf die kritischen Determinanten des Ausgangs der Erkrankung hin analysiert. Die Schwere der Grunderkrankung war der Faktor, der den Ausgang bei beiden Serien hauptsächlich beeinflußte. Frühzeitige, angemessene Antibiotikatherapie war mit einer signifikanten Verminderung sowohl der Letalität als auch der Häufigkeit der Schockentwicklung assoziiert. Angemessene Antibiotikatherapie war auch mit einer signifikanten Verminderung der Letalität assoziiert, wenn sie nach dem Eintreten des Schocks begonnen wurde. Die meisten einzelnen anti-mikrobiellen Substanzen schienen vergleichbare Effektivität zu besitzen, vorausgesetzt, der infizierende Keim war empfindlich. Es konnte nicht gezeigt werden, daß Antibiotikakombinationen wirksamer waren als Einzelsubstanzen.

     

Polyclonal bacteremia due to gram-negative rods.

The frequency of, risk factors for, and outcome of polyclonal gram-negative bacteremia are still unknown. We investigated them in a prospective cohort study of patients for whom a blood culture yielded >/=1 species of gram-negative aerobic rod. For each patient, pulsed field gel electrophoresis (PFGE) was performed on 4 colonies of each morphologic type. Episodes of bacteremia were considered polyclonal if caused by >1 PFGE type of the same species. Ten (6.5%) of 153 investigated patients had polyclonal bacteremia. Bacteremia due to nonfermenting rods was the single significant risk factor for polyclonal bacteremia. Complications were equally frequent in all patient groups. However, patients with polyclonal bacteremia received more extensive antibiotic therapy than did patients with monoclonal bacteremia. Nearly 20% of episodes of bacteremia due to nonfermenting rods were polyclonal, but it remains unclear why nonfermenting rods were more likely to cause polyclonal bacteremia than were other gram-negative rods.     

Improved prognosis for granulocytopenic patients with gram-negative bacteremia

The grave prognosis associated with gram-negative bacteremia occurring in granulocytopenic patients with cancer suggests that granulocyte transfusions are frequently indicated. We have evaluated 67 episodes of gram-negative bacteremia, studied in four consecutive antibiotic trials, in order to correlate prognostic determinants of recovery. These patients had a median absolute granulocyte count of 100/μl at the time of bacteremia. Empiric antibiotic regimens were begun at the first evidence of suspected infection. Granulocyte transfusions were employed only as clinically indicated by inadequate patient response to antibiotic therapy. Among the 29 patients who had an increase in their granulocyte count of ?100/μl over the subsequent 14 days, 27 (93 per cent) recovered whereas among 38 patients who had no appreciable increase in their granulocyte count, 21 (55 per cent) improved (p = 0.006). In this latter group of patients with no granulocyte recovery, the susceptibility of the pathogen(s) to the initial empiric antibiotic regimen was of major importance. None of four patients responded when the pathogen was resistant to both antibiotics initially utilized, six of 14 (44 per cent) patients responded when there was susceptibility to one antibiotic, and 15 of 20 (75 per cent) patients responded when there was susceptibility to both antibiotics (p < 0.025). We conclude that patients with gramnegative bacteremia and persistent granulocytopenia will often respond to antimicrobial therapy alone provided the initial choice of empiric antibiotics is appropriate and that their use is instituted promptly. Granulocyte transfusions need not be added unless clinical evaluation indicates inadequate response.     

The significance of serum-sensitive bacilli in gram-negative bacteremia.

Clinical findings from 76 patients (median age 67 years) with gram-negative bacteremia were analysed and related to the sensitivity of the blood isolates to the bactericidal activity of normal human serum. 28 strains (37%) were resistant, an equal number intermediately sensitive and 20 markedly sensitive (26%). No correlation was found between serum sensitivity and origin of the bacteremia, presence of fever or blood granulocyte count. The frequency of shock in immunocompromised patients with serum-resistant strains was 60% (6/10); in those with intermediately or markedly sensitive strains it was 44% (8/18). In the non-immunocompromised patients with resistant strains the frequency of shock was 33 (6/18) versus 10% (3/30) in those without such strains. Thus the risk of developing shock with gram-negative bacteremia seems to depend on both parasite and host factors, although in this study only the latter were statistically significant. We conclude that serum-sensitive strains can invade the blood stream in spite of the serum bactericidal activity and cause severe disease in some patients.     

Antimicrobial therapy of gram-negative bacteremia at two university-affiliated medical centers

PURPOSE: To describe antimicrobial prescribing practices and patient outcomes associated with the treatment of aerobic gram-negative rod bacteremia at two university-affiliated medical centers. SUBJECTS AND METHODS: All adult patients with gram-negative bacteremia (N = 326) who were at Stanford and University of California, San Francisco (UCSF) Hospitals from September 1, 1996 through August 31, 1997 were evaluated via retrospective review of medical records. RESULTS: Most patient characteristics were similar between institutions; however, patients at Stanford were more likely to have had a diagnosis of bone marrow transplantation, liver failure, or poor nutritional status, while more patients at UCSF had solid organ transplant, diabetes, pulmonary disease, or hypotension. The bacteriology was similar at both sites, with Escherichia coli the predominant pathogen (139 [43%] of 326). The majority of episodes were community acquired (67% [218/326]). Patients at Stanford were more likely to have been treated empirically with aminoglycosides (28% vs. 7%, P <0.001) and noncephalosporin beta-lactams (31% vs. 11%, P <0.001), while patients at UCSF were more likely to have received cephalosporins (62% vs. 29%, P <0.001) and fluoroquinolones (21% vs. 11%, P = 0.02). These patterns continued for definitive therapy. Overall mortality was 60 (19%) of 326. Several risk factors were associated with 14-day mortality, including severity of illness, neutropenia, diabetes mellitus, use of vasopressors, and empiric use of a noncephalosporin beta-lactam. CONCLUSION: Prescribing practices for the treatment of gram-negative bacteremia differed significantly in the two institutions despite similar patients and pathogens.     

Bacterial translocation and gram-negative bacteremia in patients with hematological malignancies

Between 1976 and 1982, Enterobacteriaceae and Pseudomonas aeruginosa were prospectively counted in fecal specimens from leukemic patients with gram-negative bacteremia. The strains isolated from the blood and feces of 55 patients were compared. Translocation of the dominant fecal strain of Enterobacteriaceae or P. aeruginosa was observed in 45 cases (82%) and was strongly associated with granulocytopenia of less than 10(2) cells/microliter (P less than .0001). Thirteen (81%) of 16 patients with bacteremia caused by P. aeruginosa were intestinal carriers of the same strain, whereas only 2 (5%) of 39 patients with bacteremia caused by Enterobacteriaceae were carriers of P. aeruginosa. Bacterial translocation of Enterobacteriaceae was not associated with an abnormally high fecal population of the translocating strain. Prospective quantitative and qualitative analyses of fecal flora were useful in forecasting the most probable translocating gram-negative organism in neutropenic leukemic patients with clinical signs of bacteremia.