Hyperglycemia associated with protease inhibitors in an urban HIV-infected minority patient population.

BACKGROUND: Hyperglycemia and new-onset diabetes mellitus have been reported to occur in HIV-infected patients treated with protease inhibitors. OBJECTIVE: To determine the effect of protease inhibitor therapy on serum glucose in a predominantly minority patient population. DESIGN: Retrospective record review. SETTING: Clinical HIV program of an urban Veterans Affairs medical center. PATIENTS: All HIV-infected patients receiving a protease inhibitor over a one-year period from September 1996 through August 1997. RESULTS: One hundred seventeen patients not previously known to be diabetic received protease inhibitors; seven (6%) developed symptomatic diabetes mellitus. Eight other patients had one or more serum glucose values >150 mg/dL. Mean random glucose values for patients who did not develop diabetes were higher during therapy than prior to initiation of protease inhibitors. CONCLUSIONS: Urban minority HIV-infected patients receiving combination antiretroviral therapy including a protease inhibitor may be at increased risk for the development of hyperglycemia and diabetes mellitus. Risk factors for diabetes mellitus should be identified and blood glucose monitored in all patients receiving protease inhibitors.

Vancomycin-resistant Enterococcus faecium in a Veterans Affairs Medical Center: association with antibiotic usage.

BACKGROUND: Colonization and infection with vancomycin-resistant Enterococcus faecium (VREF) has been associated with the use of vancomycin and other antibiotics in individual patients. The objective of this study was to determine the association of VREF with the aggregate usage of antibiotics on nursing units in a hospital. METHODS: This was a retrospective correlation study. A usage ratio was calculated for each parenteral antibiotic on each nursing unit as the per-bed usage by weight of that antibiotic divided by its average usage throughout the hospital. An average usage ratio (AUR) for each nursing unit was calculated as the mean of usage ratios of individual antibiotics. The AUR was used to compare the usage of antibiotics among nursing units in the hospital. The incidence of VREF infections on individual nursing units in a Veterans Affairs Medical Center was correlated with the usage of parenteral antibiotics separately and in aggregate in univariate and multivariate regression analyses. RESULTS: The AUR was strongly and positively correlated with the recovery of VREF on individual nursing units. By univariate analyses, increasing use of each antibiotic tested was associated with isolation of VREF but only clindamycin remained significant in the multivariate model. However, usage of various antibiotics was highly interrelated, and only clindamycin usage was significantly correlated with usage of all other antibiotics studied. Intensive care and acute care units and units with fewer patient beds were more likely to have patients with VREF infection than were subacute care units (p < 0.003) or larger units (p < 0.01). CONCLUSIONS: VREF infections were associated with greater aggregate antibiotic use on nursing units. Determination of antibiotic usage ratios may provide a convenient and useful tool for examining the association of antibiotic usage with other nosocomial infections.

Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS.

The study objective was to obtain preliminary information regarding the safety and efficacy of amphotericin B (AmB) lipid complex (ABLC) in the treatment of AIDS-associated cryptococcal meningitis. Of 55 patients randomly assigned to 6 weeks of therapy with ABLC (1.2-5.0 mg/[kg.d], with ascending doses for three sequential cohorts) or AmB (0.7-1.2 mg/[kg.d]), 46 received > or = 12 doses. Transfusion requirements, mean decreases in hemoglobin level, and mean increases in creatinine level were significantly greater with AmB than with ABLC. The total number of adverse events, infusion-related events, and occurrences of hypomagnesemia and hypokalemia associated with each form of therapy were similar. Among 21 recipients of ABLC at a dosage of 5 mg/kg (daily for 2 weeks and then thrice weekly for 4 weeks), symptoms and signs resolved for 18 (86%). Of those receiving > or = 12 doses of ABLC, cultures converted to negative for 8 (42%), were undeterminable for 3 (16%), and remained positive for 8 (42%) despite resolution of symptoms. Although preliminary, these data suggest ABLC has significant activity in patients with AIDS-associated cryptococcal meningitis. Because this formulation has less hematologic and renal toxicity than does AmB, further evaluation of ABLC is warranted.

Survival of nosocomial pathogenic bacteria at ambient temperature.

Staphylococcus aureus and many gram-negative rods are prevalent nosocomial pathogens. The mechanisms by which these organisms persist and spread within the hospital environment have not been clearly defined. We found that these bacteria have an extraordinary capability for survival in the environment. The viabilities of staphylococcal and gram-negative (Escherichia coli and Pseudomonas aeruginosa) isolates were assessed on three environmental surfaces: a non-nutrient surface, a woven cotton fiber, and a blood protein coagulum. The bacteria were dried on these surfaces and quantitatively subcultured over six months. The viability was consistently higher on dried blood surfaces. Viability was next highest on cotton strings. For both of these environments, staphylococci appeared to lose viability between three and six months, while E. coli and P. aeruginosa survived longer. Survival on a clean non-nutrient surface (tubes alone) for all organisms was much briefer and did not extend beyond four weeks. Such extended survival on blood and fiber surfaces, as observed in part, explains the difficulty in controlling colonization of patients by and spread of these nosocomial pathogens.

Vancomycin-dependent Enterococcus faecium isolated from stool following oral vancomycin therapy.

The isolation of clinical strains of enterococci requiring vancomycin for growth has only recently been reported. We describe the isolation of Enterococcus faecium requiring vancomycin for growth from the stool of a patient who had completed oral vancomycin therapy. Growth of the vancomycin-dependent E. faecium was supported by ristocetin and D-alanyl-D-alanine but not by daptomycin, teicoplanin, or D,L-alanine. Spontaneous revertants not requiring vancomycin occurred at a rate of 1 in 10(6). Both the vancomycin-dependent E. faecium and the revertant hybridized with a vanB gene probe and had identical contour-clamped homogeneous electrophoresis patterns. The majority of revertant colonies were resistant to teicoplanin, suggesting constitutive production of the vanB ligase. We believe the vancomycin-dependent E. faecium evolved from a vancomycin-resistant, vancomycin-independent E. faecium in the presence of high concentrations of vancomycin in the intestine.

Oral fluconazole versus amphotericin B bladder irrigation for treatment of candidal funguria.

A randomized trial was conducted to compare amphotericin B bladder irrigation (AmBBI) with oral fluconazole in terms of efficacy and safety in the treatment of candidal funguria. Fifty-three patients with two consecutive positive funal cultures of urine were randomized to undergo AmBBI (50 mg/L over 24 hours or 50 mg/L for 7 days) or to receive fluconazole (200 mg/d for 7 days). Urinary catheters were changed upon entry into the study and following therapy. Blood and urine specimens were obtained throughout the study. Candida albicans was the species isolated most frequently from urine cultures. Eradication rates for funguria at 24 hours and 5-9 days after therapy were 82.4% and 75%, respectively, with the 7-day AmBBI regimen; and 83.3% and 76.9%, respectively, with fluconazole. There were no differences in the posttherapy eradication rates between the regimens at 24 hours (P = .597) and at 5-9 days (P = .66). Candida glabrata was the predominant organism recovered from patients in the fluconazole group 5-9 days after the completion of therapy. Adverse events were limited to bladder fullness in a patient who underwent AmBBI and hypoglycemia in a patient who received concomitant therapy with fluconazole and glyburide. AmBBI (once or for 7 days) and fluconazole appear to be equally efficacious in the treatment of candidal funguria.

Antibiotic killing of bacteria: comparison of bacteria on surfaces and in liquid, growing and nongrowing.

The minimum inhibitory concentrations of antibiotics for bacterial pathogens are derived from broth suspensions (broth dilution) and from nutrient surfaces (agar dilution). These concentrations may not apply when bacteria are on a nonnutrient surface such as in a foreign body infection. We compared bacteria (Staphylococcus epidermidis and Escherichia coli) broth suspension MBCs with MBCs of the same bacteria when on a nonnutrient surface in broth the growing and nongrowing phases. Bacteria growing on cotton surfaces were much less susceptible to antibiotic killing than when freely suspended in the liquid nutrient. These results alone, independent of host factors, would explain the failure of antibiotics to eradicate infections involving bacteria on foreign body surfaces. The resistance of bacteria to antibiotic killing is not caused by a lack of antibiotic penetration to the site of the bacteria, but by an altered state of the bacteria when they are associated with a surface.

Accuracy of disincorporation for identification of vascular graft infection.

OBJECTIVE: The presence or absence of prosthetic graft incorporation with surrounding tissue was assessed relative to bacterial culture results, using enhanced microbiologic culture techniques. DESIGN: Criterion standard. SETTING: University and Veterans Affairs hospital. PATIENTS: Prosthetic samples were removed from 113 aortofemoral, extra-anatomic, infrainguinal, and hemoaccess sites at the time of vascular reoperative surgery. Harvested grafts were sonicated. Density of organisms was determined by quantitative culture. MAIN OUTCOME MEASURES: The culture result was predicted from the status of prosthetic incorporation or disincorporation as determined at surgery. For purposes of this study, any bacterial growth represented graft infection. RESULTS: Cultures positive for bacteria were obtained from 31 sites; cultures with no growth, from 82. Thirty-one of the 113 sites were disincorporated, of which 23 yielded cultures positive for bacteria, and eight, no growth. The remaining 82 sites were well incorporated, of which 74 yielded cultures negative for bacteria, and eight, bacterial growth. Sixteen (14%) incorrect predictions were noted. The concurrence of disincorporation and a culture positive for bacteria relative to all culture-positive grafts (sensitivity) was 74%. The concurrence of incorporation and cultures negative for bacteria relative to all culture-negative grafts (specificity) was 90% in prostheses implanted for longer than 2 weeks; in prostheses implanted for longer than 12 weeks, specificity was 97%. CONCLUSIONS: The surgical finding of incorporation or disincorporation accurately predicted the culture result in 89% of the sites. Disincorporation correlated with presence of bacteria in 71%; incorporation reliably excluded the presence of bacteria in 97%.

Colonization pattern of vancomycin-resistant Enterococcus faecium.

BACKGROUND: Vancomycin-resistant Enterococcus faecium is increasingly recognized as a serious problem by hospital epidemiologists. Understanding its colonization patterns may help in designing strategies to control its nosocomial spread in the hospital. METHODS: Twenty patients, selected at random, with vancomycin-resistant E. faecium isolated from cultures of various body sites were studied to determine sites of colonization. For 12 of these patients, cultures of environmental surfaces of their rooms and wards were also obtained. RESULTS: Eighteen patients (90%) had vancomycin-resistant E. faecium grown in stool cultures. In five patients (25%), vancomycin-resistant E. faecium was cultured from other sites: groins (four), popliteal fossae (three), mouth (one), and an open wound site (one). Patients with positive cultures from the groins and popliteal fossae also had growth of vancomycin-resistant E. faecium in cultures of diarrhea soiling those sites. No patients had the organism isolated from their nares. Vancomycin-resistant E. faecium grew in cultures obtained from bedside stand tables, over-bed tables, used linen, and bedside rails. CONCLUSIONS: In the 20 patients studied, colonization of vancomycin-resistant E. faecium was limited chiefly to the enteric tract. Absence of colonization of such a secluded area with poor antibiotic penetrability as the nares is encouraging. In our study, vancomycin-resistant E. faecium was isolated from various environmental surfaces from the rooms and wards of patients with vancomycin-resistant E. faecium in their stools.

Enteric eradication of vancomycin-resistant Enterococcus faecium with oral bacitracin.

The emergence of vancomycin-resistant Enterococcus faecium (VREF) has produced a therapeutic dilemma. The colonization of the intestinal tract with VREF may predispose patients to infections by this organism and may contribute to its nosocomial spread. It is reasonable to attempt to eradicate VREF from colonized patients. The optimal regimen, however, is unknown and this study was designed to evaluate the efficacy of oral regimens of vancomycin and bacitracin for the elimination of VREF from the enteric tract. Enterococcal isolates were tested for susceptibilities to vancomycin, bacitracin, and ampicillin with median minimum inhibitory concentrations of > 512 micrograms/ml, 10 units/ml, and 128 micrograms/ml, respectively. All patients were given an initial trial of oral vancomycin 125 mg every 6 h for 10 days. Those who failed oral vancomycin were then given oral bacitracin 25,000 units every 6 h for 10 days due to its favorable in vitro activity. VREF was eradicated from the stools of 42% of patients (eight of 19) receiving oral vancomycin as compared with all eight patients receiving oral bacitracin (P < 0.01). The organism recurred in two bacitracin patients (25%) 8 and 20 days after completion of therapy. Whether prior vancomycin therapy predisposed patients to colonization by VREF was also examined. Ten (53%) of 19 patients had received prior vancomycin therapy before isolation of VREF from the stool. Our data suggest that oral bacitracin may be an effective alternative to commercially available oral vancomycin for the eradication of VREF from the enteric tract.

Effect of morphine or phenobarbital on teicoplanin elimination pharmacokinetics.

Elimination kinetics following a single dose of teicoplanin in rats pre-treated with morphine sulphate (MS), phenobarbital sodium (Pb), and normal saline (NS) were determined. A microbioassay was used to measure teicoplanin levels. A significant increase in the total clearance of teicoplanin was found in rats pre-treated with MS as compared to controls (P < 0.048). Wide variability was observed in the renal and non-renal clearances of teicoplanin. The mean renal clearance for rats pre-treated with MS, Pb and NS was 0.61 +/- 0.07.mL/min/kg, 0.60 +/- 0.13 mL/min/kg, and 0.46 +/- 0.02 mL/min/kg, respectively; the mean non-renal clearance was 0.33 +/- 0.18 mL/min/kg, 0.17 +/- 0.15 mL/min/kg, and 0.08 +/- 0.03 mL/min/kg, respectively. The differences among the groups for renal and non-renal clearance were not statistically significant. The mean apparent volume of distribution of teicoplanin at steady state was significantly lower in the Pb-pre-treated rats as compared to controls (P < 0.043). The mean half-life for MS-, Pb-, and NS pre-treated groups was 8.1 +/- 3.1 h, 5.9 +/- 3.3 h, and 34.6 +/- 20.7 h, respectively. The differences in mean half-life among the groups achieved statistical significance (P < 0.016). The increase in the total clearance of teicoplanin can best be explained by an increase in both renal elimination and hepatic metabolic pathways.

Effect of antibiotics on endotoxin release from gram-negative bacteria.

Antibiotics may inhibit bacterial growth or may kill bacteria by inhibiting cell wall synthesis or protein synthesis. The amount of endotoxin released during antibiotic action has been found to be clinically important. Nine antibiotics, representing seven classes, were studied for the amounts of endotoxin released during their action on susceptible strains of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa. Staphylococcus aureus, which produces no endotoxin, was used as a control organism. Aztreonam induced the highest release of endotoxin, whereas other antibiotics such as imipenem and the quinolones induced the lowest release of endotoxin. Although the quantities of endotoxin released are not easily explained from the established mechanisms of antibiotic action, our findings may have implications for therapy of the acutely ill, septic patient in whom release of large quantities of endotoxin may be catastrophic.

Optimal method for culturing vascular prosthetic grafts.

Vascular prosthetic infection may be underrecognized when identified by standard culture techniques. Improved microbiologic methodology may enhance detection of bacteria in prosthetic graft specimens, and thus may alter clinical decisions. Quantitative culture techniques were employed to compare three methods of enhancing bacterial recovery from Dacron graft cylinders seeded with commonly encountered bacterial pathogens. Methods included: (1) ultrasonic bath treatment, (2) direct ultrasonic disruption, and (3) agitation on a Vortex mixer. Ultrasonic bath treatment released bacteria with colony counts that were consistently greater by 1 log than direct ultrasonic disruption and Vortex agitation. Direct ultrasonic disruption at high energy levels selectively killed gram-negative bacteria by as much as a 4 log decrease in viable organisms. Agitation (Vortex mixing) of the specimen produced the lowest counts among the three methods tested. These data would indicate that a 5-min ultrasonic bath treatment was the optimal method of preparation of vascular prostheses for bacterial culture.

Involvement of Gardnerella vaginalis in urinary tract infections in men.

Fifteen male patients from whose urine samples Gardnerella vaginalis was isolated (clinical incidence of 0.1%) were evaluated for clinical signs and symptoms of urinary tract infection and modality of acquisition of the organism. Ten of 15 (67%) patients were symptomatic or had signs of inflammation as manifested by an increased number of urinary neutrophils. One patient had two bouts of infection caused by this organism which required two courses of antibiotic therapy. Colonies of diphtheroidlike organisms found in urine cultures should not be ignored as insignificant but should be further investigated to determine whether G. vaginalis is present.

Vitamin K supplementation during prophylactic use of cefoperazone in urologic surgery.

Cefoperazone, an antibiotic commonly used for prophylaxis of infection, has been associated with hypoprothrombinemia and bleeding. To reduce the risk of bleeding, co-administration of vitamin K has been advised. We reassessed the need for vitamin K use in a retrospective analysis of 50 patients undergoing urologic procedures and who had received cefoperazone for three days to prevent infection. Eleven of 50 patients were given vitamin K because of liver or renal disease. Prothrombin time was not elevated in any of the 50 patients analyzed. We conclude that routine use of vitamin K with cefoperazone for perioperative prophylaxis of infection may be unwarranted in patients without identified risk for bleeding.

A comparison of antimicrobial activity of ofloxacin, L-ofloxacin, and other oral agents for respiratory pathogens.

The attainable inhibitory ratios (AR) for oral antibiotics were calculated by using literature reports of concentrations attained in respiratory secretions for amoxicillin-clavulanic acid (AMX/CA), ofloxacin (OFL), L-ofloxacin (L-OFL), cefuroxime (CEFU), ciprofloxacin (CIP), and enoxacin (ENO), and using microdilution minimum inhibitory concentration data of these antimicrobials against the common bacterial respiratory pathogens. AR of each antibiotic against the pathogens was expressed as multiples of the MICs achieved at the respiratory site. Bacteria tested included Staphylococcus aureus, group-A and group-B streptococci, Viridans streptococci, Streptococcus pneumoniae, Brahamella catarrhalis, Klebsiella pneumoniae, Eikenella corrodens, Haemophilus influenzae, H. parainfluenzae, Pseudomonas aeruginosa, and Legionella pneumophila. The antimicrobials with the narrowest spectrum of activity were amoxicillin-clavulanic acid and cefuroxime which had high attainable inhibitory ratios only against Gram-positive cocci. Ofloxacin and L-oflaxacin were among the quinolones with the highest overall ARs against respiratory pathogen, including, L. pneumophila, H. influenzae, and B. catarrhalis. All agents showed no, or inadequately low ARs for P. aeruginosa.

Fungemia observations of peripheral tissue clearance in humans.

Patients with fungemia, mainly due to Candida albicans, had cultures repeated from arterial and venous sites to determine yeast cell clearance during fungemia. Of the 48 patients, 37 had repeat positive cultures (36 arterial and venous samples; one venous culture). Additionally, 24 patients had arterial and venous samples cultured quantitatively. An average of 9.1 colony forming units (CFU) ml-1 was isolated from arterial samples and 5.5 CFU ml-1 from venous samples (60% of arterial, P < 0.01). This suggest that arterial fungal densities exceed venous densities and that peripheral tissues clear 40% of yeasts.

Escherichia coli resistant to ampicillin/sulbactam.

Escherichia coli strains resistant to ampicillin/sulbactam from hospitals in 4 different geographic locations were examined with respect to type and amount of beta-lactamase produced. A total of 5 strains was examined from each region. The isoelectric points of all of the involved beta-lactamases were 5.4, corresponding to TEM-1. Km and Vmax values of the beta-lactamases among the clinical isolates resembled those from the control TEM-1 strain. In an 18-hour broth culture the highly resistant isolates produced 3 times more beta-lactamase as compared to the ampicillin/sulbactam-susceptible isolates. However, the highly resistant strains contained approximately the same amount of plasmid DNA (size of > 6,500 bp) as the susceptible isolates. In transformation experiments, both the resistance and the degree of resistance appeared to have been transferable by plasmids. The mechanism for resistance is likely to be a baseline overproduction of TEM-1 beta-lactamase due to either an alteration in the control of gene expression or simply to an increase in the number of copies of the beta-lactamase gene in the plasmids.