Nosocomial bloodstream infections caused by gentamicin-resistant gram-negative bacilli

Gentamicin resistance has emerged since 1971 among gram-negative bacilli isolated at the University of Virginia Hospital. Of 9,169 gram-negative bacilli isolated in 1971, 0.8 per cent were resistant to gentamicin by disc sensitivity testing. Of 7,817 isolates in 1975, 7.7 per cent were resistant. Approximately 20 per cent of the Klebsiellae had a minimum inhibitory concentration (MIC) ≥ 16 μg/ml of gentamicin.     

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.     

Recurrent gram-negative bacteremia

PURPOSE: Recurrent gram-negative bacteremia is defined as two or more episodes of bacteremia occurring in the same patient with an infection-free interval between each episode. Our purpose was to identify patients with recurrent gram-negative bacteremia in order to define possible risk factors for its recurrence. PATIENTS and METHODS: During a recently completed prospective study of all episodes of gram-negative bacteremia at the Buffalo Veterans Administration Center between April 1, 1984, and May 31, 1987, 35 patients with 74 episodes of gram-negative bacteremia were identified. The following information was obtained from all 35 patients: age, service, date of hospital admission, date of the bacteremia, underlying diseases, initial antimicrobial therapy, focus of infection, the presence or absence of shock, antimicrobial susceptibility of the blood isolate, and outcome. RESULTS: All 35 patients were men, had a mean age of 69 years, and all had one or more underlying diseases; 45 percent had a malignancy. The duration of time between a pair of episodes was four weeks or more for 74 percent of 38 pairs of episodes. In 25 of 38 (66 percent) pairs of episodes, the focus of infection was the same; in 80 percent of these 25 pairs, the urinary tract was the focus. Overall, the urinary tract was the focus of gram-negative bacteremia in almost 50 percent. Escherichia coli was the single most common organism isolated (28 percent of all episodes), followed by Proteus mirabilis (17.5 percent) and Pseudomonas aeruginosa (17.5 percent). Six of 35 (17 percent) patients died due to gram-negative bacteremia; five of these six had a respiratory tract focus of infection. CONCLUSIONS: In a population of veterans, recurrent gram-negative bacteremia was identified in almost 10 percent of all patients with gram-negative bacteremia during a 37-month study period. Recurrent gram-negative bacteremia most frequently occurred in the setting of underlying malignancy with the urinary tract as a common focus of infection. The mortality rate of 17 percent was similar to that of all patients with gram-negative bacteremia reported in previous studies.     

Interactions of phagocytic and bacterial cells in patients with bacteremia caused by gram-negative rods

The phagocytic and bactericidal functions of polymorphonuclear leukocytes and monocytes and the opsonic activity of serum from patients with gram-negative bacteremia were compared with those of cells and serum from healthy donors and control patients. Leukocytes from five of 20 patients showed diminished phagocytic capacity. Leukocytes from three of 12 patients had decreased chemotactic activity. Eleven of 37 blood culture isolates were inefficiently phagocytized after opsonization in homologous patient serum. However, in no instance was the opsonic capacity of patient serum significantly lower than that of control serum. In the serum of some patients, an increase in heat-stable opsonins was found during the course of infection. Resistance to opsonization of strains of Escherichia coli correlated with the presence of K capsular polysaccharide. It was concluded that both impaired leukocyte function and ineffective opsonization play a role in the pathogenesis of gram-negative bacteremia. Heat-stable opsonins (presumably specific antibodies) appear to be necessary for effective phagocytosis of bacilli that cause gram-negative bacteremia.     

Effects of IgM and IgG antibody in patients with bacteremia due to gram-negative bacilli.

Earlier studies, which indicated that high titers of O-specific antibody to the patient's infecting organism in acute-phase serum specimens were not associated with a decrease in the frequency of subsequent shock and death in bacteremia due to gram-negative bacilli, were reexamined for evaluation of the protective activity of specific IgG and IgM antibody. Titers of hemagglutination antibody and levels of IgM, determined by indirect immunofluorescent staining of the patient's infecting organism, as well as hemagglutination titers after reduction of serum with 2-mercaptoethanol and IgG levels, correlated closely (P less than 0.001). High titers of IgG antibody to the patient's infecting organism in acute-phase specimens were associated with a significant reduction in the frequency of shock and death in bacteremia. In contrast, high titers of IgG antibody were not associated with a diminution in the frequency of shock and death. The previously demonstrated protective activity of antibody to an antigen, Re lipopolysaccharide, shared by most gram-negative bacilli was reconfirmed and shown to be independent of the protective activity of O-specific IgG antibody.     

Wounds caused by corn-harvesting machines: an unusual source of infection due to gram-negative bacilli

The infectious complications in 23 patients with mutilating wounds due to trauma during corn harvesting were compared with those in 41 patients with factory-related hand injuries of similar severity. Initial cultures revealed bacterial growth in 89% of the agricultural wounds and in 63% of the factory wounds. A mean of 3.8 initial bacterial species were isolated per corn-harvesting wound vs. 0.9 species per factory wound. Gram-negative rods were recovered from 81% of the agricultural wounds; the commonest of these organisms were Enterobacter species and Xanthomonas maltophilia. Only 7% of factory-wound cultures grew gram-negative rods. Osteomyelitis, all with gram-negative rods, developed in five (22%) of the patients with farm injuries but did not occur in patients with factory wounds. More gram-negative rods were recovered from environmental cultures of corn-harvesting machines and corn plants than from those of factory machinery.     

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.     

Amikacin therapy of gram-negative bacteremia and meningitis. Treatment in diseases due to multiple resistant bacilli.

The therapeutic efficacy of amikacin was evaluated in patients with serious hospital-acquired infections caused by Gram-negative bacilli susceptible to amikacin, but usually resistant to kanamycin, gentamicin, and tobramycin. The infections for which amikacin was given were Gram-negative bacteremia in 15 patients and Gram-negative meningitis in two patients. Therapy with amikacin resulted in a cure in 13 patients, improvement in 1, and failure in 3. Continuous intravenous infusion of amikacin yielded a high cerebrospinal fluid to serum ratio of amikacin in one case of meningitis and intrathecally administered amikacin yielded high ventricular fluid levels in another case of meningitis. The emergence of resistance to amikacin was noted in one patient treated with amikacin in whom Serratia bacteremia persisted. Treatment with amikacin was usually tolerated well. This study indicates that amikacin is an effective antibiotic in the treatment of serious Gram-negative infections caused by gentamicin-resistant organisms.     

New treatment options for infections caused by multiresistant strains of Pseudomonas aeruginosa and other nonfermenting gram-negative bacilli

Hospital-acquired infections are one of the most important challenges to patient safety, especially in critical care units. The use of broad-spectrum antibiotics results frequently in multidrug-resistant pathogens. Therefore, we are attending to increased rates of multidrug-resistant microorganisms, especially gram-negative bacilli, that have been associated with prolonged hospital stays, higher costs, and increased mortality. The most important multidrug-resistant pathogens are PSEUDOMONAS AERUGINOSA and ACINETOBACTER BAUMANNII. There has been an important but as yet unsuccessful effort to develop new drugs to treat these pathogens. Nevertheless, old, very well known drugs, such as polymyxins, administered intravenously and aerosolized, have been revisited. Future options include immunotherapy or the continuous infusion of antibiotics. It is also important to emphasize the rational use of antibiotics to diminish the appearance of multiresistant pathogens.     

Endocarditis due to anaerobic gram-negative bacilli

A case of Bacteroides fragilis endocarditis which developed after appendicitis is discussed. Combined therapy with tetracycline and erythromycin for over 18 months, and therapy with several other agents given over a period of more than two years in all, failed to eradicate the infection. The organism in this case was markedly resistant to penicillin, intermediate in susceptibility to vancomycin, and sensitive to tetracycline, erythromycin, lincomycin, 7-chlorolincomycin, chloramphenicol, rifampin and metronidazole. Only metronidazole (Flagyl®), however, demonstrated bactericidal activity. Unfortunately, this drug was not available at the time of this patient's illness for therapeutic evaluation.A review of the 37 published cases of endocarditis due to gram-negative anaerobic bacilli revealed that these organisms appear to be more invasive and destructive than “viridans” streptococci. Major embolie phenomena were prominent complications. The over-all mortality was 46 per cent. If the penicillin-susceptible organisms alone are considered, the mortality is probably less than 20 per cent. However, because of the lack of an agent with bactericidal activity against B. fragilis (which is usually resistant to penicillin), the mortality caused by this organism is considerably greater.