William R. McCabe

Gram-negative bacteremia: IV. Re-evaluation of clinical features and treatment in 612 patients

Clinical features and specific aspects of treatment were evaluated in 612 patients with gram-negative bacteremia observed over a 10 year period. Coagulation abnormalities or thrombocytopenia were observed in 64 per cent of the patients. Evidence of disseminated intravascular coagulation (DIC) was found in approximately 10 per cent of them but was of sufficient severity to be associated with subcutaneous or visceral bleeding in 3 per cent of them. The frequency of coagulation abnormalities, other than DIC, was greater in patients with more severe underlying disease but DIC occurred with similar frequency irrespective of the severity of underyling host disease. Coagulation abnormalities of all types were associated with increased fatality rates. Hypothermia was noted in 13 per cent of the patients at the onset of bacteremia but was transient and was not associated with increased fatality. Failure to mount a febrile response greater than 99.6 degrees F within the first 24 hours of bacteremia was associated with a significant increase in fatality rates. Prior corticosteroid therapy diminished the febrile response to bacteremia. Age, underlying host disease, granulocytopenia, congestive heart failure, diabetes mellitus, renal insufficiency, nosocomial infections, and antecedent treatment with antibiotics, corticosteroids, and antimetabolites significantly increased fatality rates. Appropriate antibiotic treatment reduced the fatality rate of those with bacteremia by approximately one-half among patients in each category of severity of underlying host disease. In addition, it was shown that early appropriate antibiotic therapy also reduced the frequency with which shock developed by one half. Even after development of shock, appropriate antibiotic therapy significantly reduced fatality rates. The use of combinations of antibiotics could not be demonstrated to significantly improve survival rates. Minimal differences in therapeutic efficacy could be demonstrated between individual antibiotics and various combinations of antimicrobials. Shock occurred in approximately 40 per cent of the patients and its frequency was not influenced by the species of etiologic agent. Contrary to previous reports, corticosteroid therapy in patients with shock did not enhance survival and treatment with an average of 4.0 g/day of hydrocortisone or its equivalents was associated with a significant increase in fatality rates.

Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization

Gram-negative nosocomial pneumonia may result from retrograde colonization of the pharynx from the stomach, and this may be more likely when the gastric pH is relatively high. We studied the rate of nosocomial pneumonia among 130 patients given mechanical ventilation in an intensive care unit who were receiving as prophylaxis for stress ulcer either sucralfate (n = 61), which does not raise gastric pH, or conventional treatment with antacids, histamine type 2 (H2) blockers, or both (n = 69). At the time of randomization to treatment, the two groups were similar in age, underlying diseases, and severity of acute illness. Patients in the sucralfate group had a higher proportion of gastric aspirates with a pH less than or equal to 4 (P less than 0.001) and significantly lower concentrations of gram-negative bacilli (P less than 0.05) in gastric aspirates, pharyngeal swabs, and tracheal aspirates than did patients in the antacid-H2-blocker group. The rate of pneumonia was twice as high in the antacid-H2 group as in the sucralfate group (95 percent confidence interval, 0.89 to 4.58; P = 0.11). Gram-negative bacilli were isolated more frequently from the tracheal aspirates of patients with pneumonia who were receiving antacids or H2 blockers. Mortality rates were 1.6 times higher in the antacid-H2 group than in the sucralfate group (95 percent confidence interval, 0.99 to 2.50; P = 0.07). Although our results fell just short of statistical significance when they were analyzed according to intention to treat, they suggest that agents that elevate gastric pH increase the risk of nosocomial pneumonia in patients receiving ventilation by favoring gastric colonization with gram-negative bacilli. We conclude that in patients receiving mechanical ventilation, the use of a prophylactic agent against stress-ulcer bleeding that preserves the natural gastric acid barrier against bacterial overgrowth may be preferable to antacids and H2 blockers.

Bacterial infections in adult patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex

Sixty-four episodes of bacterial infection were identified over a 44-month period in 16 of 28 patients with the acquired immune deficiency syndrome (AIDS) and 14 of 31 patients with AIDS-related complex. Nineteen of the 30 infected patients were parenteral drug abusers, 10 were from Caribbean Islands and had no identified risk factor, and one was a homosexual male. Fourteen patients had 21 episodes of community-acquired pneumonia: Streptococcus pneumoniae (10), Haemophilus influenzae (three), other Haemophilus species (three), group B beta-hemolytic streptococci (one), Staphylococcus aureus (one), Branhamella catarrhalis (one), Legionella pneumophila (one), and Mycoplasma pneumoniae (one). Seven patients had eight episodes of nosocomial pneumonia caused by gram-negative bacilli. Twenty-five episodes of community-acquired bacteremia and nine episodes of nosocomial bacteremia were associated with specific sites of infection. Other infections included meningitis (two), urinary tract infection (one), and abscesses involving subcutaneous and deep tissues (12). Sixteen patients had recurrent infections; 11 of these had or eventually had AIDS. Community-acquired bacterial infections in patients with AIDS or AIDS-related complex are common and may be recurrent but have low fatality rates. In comparison, nosocomial bacterial infections occur primarily in patients with AIDS and have high fatality rates.

Activation of the Properdin Pathway of Complement in Patients with Gram-Negative Bacteremia

To determine the pathway used for activation of complement component C3, serum levels of components C1, C4, C2, C3, C5, C6, and C9 and two properdin factors, properdin and factor B, were measured in 42 patients with gram-negative bacteremia, in 19 of whom shock subsequently developed. Mean levels of the classical components C1, C4, and C2 in bacteremic patients in whom shock subsequently developed did not differ significantly (p greater than 0.05) from those of patients with uncomplicated bacteremia. Levels of properdin, factor B and C3, C5, C6, and C9 were significantly (p less than 0.05) decreased in patients with shock in comparison with those with uncomplicated bacteremia. Taken together, these findings are consistent with activation of C3 and the terminal complement sequence, C5-C9, occurring primarily by the properdin pathway, in patients with gram-negative bacteremia eventuating in shock. Biologically active products released during activation of C3-C9 may contribute to the development of shock.

Type-Specific and Cross-Reactive Antibodies in Gram-Negative Bacteremia

Abstract Antibody titers to O-specific and two shared cross-reactive antigens (common entero-bacterial antigen [CA] and a determinant [Re] of rough bacilli) were related to the frequency of shock or a fatal outcome in 175 patients with gram-negative bacteremia. High titers of O antibody did not prevent development of bacteremia and were associated with only a very slight decrease in the frequency of shock and death. The height of antibody titers to CA also did not correlate with the frequency of shock or a fatal outcome. In contrast, both shock and death were 1/3 as frequent among patients with high titers (1:80 or above) of Re antibody. The apparent protective effect of Re antibody was independent of any contribution of O antibody. These observations, coupled with prior animal studies, suggest that enhancement of resistance to enterobacteria might be accomplished by immunization with shared cross-reactive antigens.

Contamination of Mechanical Ventilators with Tubing Changes Every 24 or 48 Hours

We studied the contamination of ventilator circuits in order to assess the need for daily changes of tubing. Patients requiring continuous mechanical ventilation were randomly selected for tubing changes at 24 hours (Group 1) or at 48 hours (Group 2). Samples of inspiratory-phase gas from ventilators with standardized settings were cultured according to the tube-broth method of Edmondson and Sanford. The frequency of positive cultures from 128 ventilators in Group 1 (30 per cent) was not significantly different from that for 112 ventilators in Group 2 (32 per cent). Gram-negative bacteria were most frequently isolated from patients sputum and ventilator inspiratory-phase gas, but no species predominated in either group of patients. Further studies performed with the Aerotest and Andersen air samplers confirmed that the levels of inspiratory-phase-gas contamination were low in both groups. In addition, quantitative analysis of colonization of the tubing demonstrated no significant increase in colonization between 24 and 48 hours. The absence of a significant difference in inspiratory-phase-gas contamination or tubing colonization suggests that ventilator tubing need be changed only every 48 hours.

Contaminated medication nebulizers in mechanical ventilator circuits: Source of bacterial aerosols

The contamination rates of medication nebulizers inserted into mechanical ventilator circuits were studied. Semiquantitative techniques were used to sample the reservoir fluid from in-line nebulizers during the first 24 hours after a circuit change. In the initial survey, high levels of contamination (organism concentrations above 10(3)/ml) were present in 13 (68 percent) of the 19 nebulizer reservoirs, and bacterial aerosols were produced by 10 (71 percent) of 14 nebulizers. Gram-negative bacilli were the predominant organisms isolated. Nebulizer contamination originated primarily from reflux of contaminated condensate in the ventilator circuit. When nebulizers were cleaned after each treatment, a reduced rate of contamination was found. Small bacterial aerosols (less than 3 microns in size) were produced in vitro after inoculation of nebulizers with gram-negative bacilli in concentrations isolated from in-use nebulizers. Contaminated in-line medication nebulizers generate small-particle bacterial aerosols that may increase the risk of ventilator-associated pneumonia and therefore should be cleaned or disinfected after each treatment rather than every 24 hours.

A large outbreak of infections caused by a strain of staphylococcus aureus resistant to oxacillin and aminoglycosides

An extensive outbreak of nosocomial infections caused by oxacillin- and aminoglycoside-resistant Staphylococcus aureus (OARSA) occurred over a 16 month period. A total of 349 isolates of OARSA were obtained from 174 patients. Colonization with OARSA was found in 92 patients. There was 120 infections in 82 patients; 50 were surgical wound infections, 13 were nonsurgical wound infections, six were pneumonias, 15 were urinary tract infections, 12 were intravenous site infections, and there were 19 episodes of bacteremia (seven transient, 12 persistent). In patients with persistent bacteremia, the mortality rate was 33 percent. In patients treated for persistent bacteremia with vancomycin, the survival rate was 80 percent. Infections were highly associated with the surgical intensive care unit, and 90 percent of the isolates of OARSA tested had the same phage-type. Elderly patients with significant underlying disease, a history of previous surgery or of prior antimicrobial therapy appeared to be at increased risk for OARSA infections. OARSA were resistant to multiple antibiotics besides oxacillin, but all isolates were sensitive to vancomycin and rifampin. Three surgical intensive care unit nurses were found to be nasal carriers of OARSA, and one nurse had dermatitis of both hands colonized with OARSA. Following the removal of these nurses from the surgical intensive care unit and the institution of strict infection control measures, the number of OARSA infections and colonizations decreased to less than one per month. OARSA produces serious nosocomial disease, and epidemiologic intervention was effective in controlling this outbreak.

Limitations of the Usefulness of the Limulus Assay for Endotoxin

Abstract Gelation of lysates of amebocytes of the horseshoe crab has been proposed as a highly sensitive and specific bioassay for endotoxin that might be of diagnostic value in infections due to gram-negative bacteria. To assess the diagnostic value of the test and evaluate the role of endotoxin in such infections, limulus assays were performed on 694 specimens collected during 344 episodes of suspected bacteremia and compared with qualitative and quantitative blood cultures. Positive assays were obtained from 28 of 65 patients (43 per cent) with bacteremia due to gram-negative bacilli and in 11 of 43 patients (26 per cent) with localized infections due to gram-negative organisms. However, the occurrence of positive assays in eight of 22 patients (36 per cent) with infections due to gram-positive bacteria, who had no concomitant infections with gram-negative organisms, casts doubt on the diagnostic value of the assay. In addition, no correlation was found between positive assays and the number of circula...

Serum Complement Levels in Bacteremia Due to Gram-Negative Organisms

Abstract Mean (± S.D.) levels of C3 did not differ significantly between 75 control patients (141.4 ± 22 mg per 100 ml) and 68 patients with bacteremia due to gram-negative organisms(132 ± 50 mg per 100 ml). In the 41 patients with uncomplicated bacteremia the mean C3 levels (151 ± 51 mg per 100 ml) did not differ from values in controls; however, a significant reduction in C3 levels was observed in 26 patients with shock (105 ± 31 mg per 100 ml) and the 19 patients who died (98 ± 38 mg per 100 ml) of bacteremia (p less than 0.001). The frequency of occurrence of shock or fatal outcome tended to parallel the degree of lowering of C3 levels in serum specimens obtained shortly after the onset of bacteremia.