Successful treatment of persistent vancomycin-resistant Enterococcus faecium bacteremia with linezolid and gentamicin.
Explore the source record for details and available documents.
Acetamides↗
Biomedical subjects
G A Noskin
Publications and source records attributed to G A Noskin.
Medical and economic benefit of a comprehensive infection control program that includes routine determination of microbial clonality.
Nosocomial infections are a major part of the problem of reemerging pathogens causing infectious diseases, affecting 5% of patients hospitalized in the United States during 1995. We assessed the medical and economic effects on the overall nosocomial infection rate of an intervention that provided an enhanced, integrated infection control program, including an in-house molecular typing laboratory capability to rapidly assess microbial clonality. Data on nosocomial infections for 24 months prior to the change in approach to infection control were compared with data from the 24 months immediately following implementation of the new program. Infections per 1,000 patient-days and percentage of hospitalized patients in whom nosocomial infection developed were assessed. Overall, nosocomial infections per 1,000 patient-days decreased more than 10% (P = .027), and percentage of patients with nosocomial infection decreased 23% during the post-intervention period compared with the previous control 24 months. This translated to a mean reduction of some 270 patients per year with nosocomial infection, and lowering of actual health care costs for our institution by $4,368,100 over the 2 years of the intervention.
Cross Infection↗
Enterococcus faecium bacteremia: does vancomycin resistance make a difference?
BACKGROUND: Enterococcus faecium has received increased attention, primarily due to the emergence of vancomycin resistance. The purpose of this investigation was to study the epidemiological characteristics of vancomycin-resistant E faecium (VRE) bacteremia and to determine the clinical impact of vancomycin resistance on the outcome of patients with this infection. METHODS: We retrospectively analyzed the clinical features and outcome of 53 patients with E faecium bacteremia. RESULTS: From January 1992 until December 1995, there were 32 episodes of bacteremia caused by vancomycin-susceptible E faecium (VSE) and 21 caused by VRE. An intra-abdominal site was the most common source of bacteremia in both groups. All of the VRE and 78% of VSE bacteremia cases were nosocomially acquired. Previous administration of vancomycin was associated with VRE bacteremia (P<.001), as were indwelling bladder catheters (P=.01). Fifty-nine percent of the patients with VSE bacteremia survived vs 24% with VRE (P=.009), despite similar severity-of-illness scores. In 62% of the patients with VRE sepsis, death was related to the bacteremia (P=.01). Patients infected with VRE had longer hospitalizations than those with VSE (34.8 vs 16.7 days, respectively) (P=.004), were more likely to be on the medical service (P=.03), and on the average, had hospitalization costs of more than $27,000 per episode than did patients with VSE bloodstream infection ($83,897 vs $56,707, respectively) (P=.04). CONCLUSIONS: Vancomycin-resistant E faecium bacteremia is a complication of prolonged hospitalization in debilitated patients. Vancomycin resistance has a negative impact on survival in patients with E faecium bacteremia and leads to higher health care costs.
Anti-Bacterial Agents↗
Recent advances in the management of fungal infections.
Explore the source record for details and available documents.
Aspergillosis↗
Prevention of infection in immunocompromised hosts.
The prevention of infection in patients with cancer has changed tremendously over the last decade, but remains in evolution. Despite many clinical trials examining the role of antibacterial, antifungal, and antiviral prophylaxis, there is still discussion among physicians about not only which patients require prophylaxis, but also the optimal regimen. Nevertheless, many of these regimens offer the hope to prevent infection in patients with underlying neoplastic diseases. There is no therapy that is uniformly effective in all settings. This is generally due to the severity of the defects in host defenses and the virulence of the microorganism. Hopefully, the future will hold many new therapeutic options to help prevent infection in patients with cancer.
Bacterial Infections↗
The utility of aminoglycosides in an era of emerging drug resistance.
As the problem of global antibiotic resistance continues to worsen, aminoglycosides have assumed increasing importance in clinical practice. Their broad antimicrobial spectrum, rapid bactericidal action, and ability to act synergistically with other drugs have made them especially useful in the treatment of serious nosocomial infections. However, as with other drugs, their overuse and misuse leads to the development of resistance in important microbial pathogens. The appropriate use of the aminoglycosides is essential to assure their continued efficacy. Therefore, physicians must familiarize themselves with both the clinical indications and the limitations of these drugs if they are to remain efficacious in the years to come.
Aminoglycosides↗
Management of fluoroquinolone resistance in Pseudomonas aeruginosa--outcome of monitored use in a referral hospital.
We evaluated a strategy designed to improve useful activity of ciprofloxacin against Pseudomonas aeruginosa. Following changes in antimicrobial agent use made by the institutional Pharmacy and Therapeutic Drug Committee, monthly drug usage and microbial susceptibility records from June 1992 through October 1995 were reviewed. From July 1992 through October 1992 (Period 1), ciprofloxacin and ofloxacin usage represented 95 and 5% of total quinolone doses; from December 1992 to March 1993 (Period 2), ciprofloxacin represented 19%; from July 1993 to October 1993 (Period 3), ciprofloxacin usage represented 85%; from July 1994 to October 1994 (Period 4), ciprofloxacin represented 95%; and from July 1995 to October 1995 (Period 5), ciprofloxacin and ofloxacin respectively represented 98 and 2% of total quinolone doses. Comparison of the anti-pseudomonal activity of the two fluoroquinolones to ofloxacin use, ciprofloxacin use and total quinolone use during the entire observational period showed the highest (negative) correlation with ofloxacin use versus ofloxacin activity (y = -15.04x + 1367.99, r2 = 0.06, w = 0.126). Increased use of quinolones plus a change to primarily ofloxacin usage appeared to adversely affect the activity of both ofloxacin and ciprofloxacin against P. aeruginosa.
Anti-Infective Agents↗
Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia.
We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.
Adolescent↗
Amphotericin B colloidal dispersion for treatment of candidemia in immunocompromised patients.
The efficacy and safety of amphotericin B colloidal dispersion (ABCD; Amphotec, Sequus Pharmaceuticals, Menlo Park, CA), a lipid complex of amphotericin B, were evaluated in immunocompromised patients with candidemia. These patients were recruited from five open-label clinical trials of ABCD therapy for fungal infections subsequent to bone marrow transplantation, hematologic malignancies, solid tumors, solid-organ transplantation, or other severe underlying disorders. ABCD was given intravenously in a median daily dose of 3.9 mg/kg for < or =72 days. Response rates were as follows: 53% overall (n = 88), 66% for patients with candidemia alone (n = 67), and 14% for patients with disseminated candidemia (n = 21). Nephrotoxicity occurred in 16% of patients, with either doubling of the baseline serum creatinine level or an increase of > or =1 mg/dL or a > or =50% decrease in calculated creatinine clearance. On average, there were no significant changes in the levels of serum creatinine or bilirubin from baseline to the end of treatment. In conclusion, ABCD was safe and effective for treating immunocompromised patients with candidemia.
Adolescent↗
Treatment of invasive fungal infections in renally impaired patients with amphotericin B colloidal dispersion.
Amphotericin B colloidal dispersion (ABCD) is a new formulation of conventional amphotericin B designed to minimize drug distribution in the kidney and reduce nephrotoxicity. We studied the safety and efficacy of ABCD in 133 renally compromised patients with invasive fungal infections. Patients had either nephrotoxicity from amphotericin B or preexisting renal disease. Intravenous treatment with ABCD (4 mg/kg of body weight daily) was administered for up to 6 weeks. Evaluations included clinical response to treatment and adverse events, with emphasis on changes in serum creatinine levels. ABCD did not appear to have an adverse effect on renal function: mean serum creatinine level tended to decrease slightly with days on therapy, and increases were not dose related. Complete or partial response to treatment was reported for 50% of the 133 intent-to-treat patients and 67% of the 58 evaluable patients.
Adolescent↗
Thirteen-year evolution of azole resistance in yeast isolates and prevalence of resistant strains carried by cancer patients at a large medical center.
Drug resistance is emerging in many important microbial pathogens, including Candida albicans. We performed fungal susceptibility tests with archived isolates obtained from 1984 through 1993 and fresh clinical isolates obtained from 1994 through 1997 by testing their susceptibilities to fluconazole, ketoconazole, and miconazole and compared the results to the rate of fluconazole use. All isolates recovered prior to 1993 were susceptible to fluconazole. Within 3 years of widespread azole use, we detected resistance to all agents in this class. In order to assess the current prevalence of resistant isolates in our hematologic malignancy and transplant patients, we obtained rectal swabs from hospitalized, non-AIDS, immunocompromised patients between June 1995 and January 1996. The swabs were inoculated onto sheep's blood agar plates containing 10 microg of vancomycin and 20 microg of gentamicin/ml of agar. One hundred one yeasts were recovered from 97 patients and were tested for their susceptibilities to amphotericin B, fluconazole, flucytosine, ketoconazole, and miconazole. The susceptibility pattern was then compared to those for all clinical isolates obtained throughout the medical center. The antifungal drug histories for each patient were also assessed. The yeasts from this surveillance study were at least as susceptible as the overall hospital strains. There did not appear to be a direct linkage between prior receipt of antifungal agent therapy and carriage of a new, drug-resistant isolate. Increased resistance to newer antifungal agents has occurred at our medical center, but it is not focal to any high-risk patient population that we studied. Monitoring of susceptibility to antifungal agents appears to be necessary for optimizing clinical therapeutic decision making.
Antifungal Agents↗
Comparison of genomic methods for differentiating strains of Enterococcus faecium: assessment using clinical epidemiologic data.
Genomic DNA extracted from 45 vancomycin-resistant Enterococcus faecium (VRE) isolates was cleaved with HindIII and HaeIII and subjected to agarose gel electrophoresis. The ability of this method (restriction endonuclease analysis [REA]) to distinguish strains at the subspecies level was compared with results previously determined by pulsed-field gel electrophoresis (PFGE). Chart reviews were performed to provide a clinical correlation of possible epidemiologic relatedness. A likely clinical association was found for 29 patients as part of two outbreaks. REA found 21 of 21 isolates were the same type in the first outbreak, with PFGE calling 19 strains the same type. In the second outbreak with eight patient isolates, HindIII found six were the same type and two were unique types. HaeIII found three strains were the same type, two strains were a separate type, and three more strains were unique types, while PFGE found three were the same type and five were unique types. No single "ideal" method can be used without clinical epidemiologic investigation, but any of these techniques is helpful in providing focus to infection control practitioners assessing possible outbreaks of nosocomial infection.
Anti-Bacterial Agents↗
Vancomycin-resistant enterococci: clinical, microbiologic, and epidemiologic features.
Enterococci have emerged as important nosocomial pathogens with increasing antimicrobial resistance. Within the past 5 years, vancomycin-resistant strains have disseminated throughout the United States and Europe. Many of these organisms are also highly resistant to beta-lactams and aminoglycosides, making them virtually untreatable. Because optimal therapy for these infections is unknown, attributable mortality rates for patients with vancomycin-resistant enterococcal bacteremia are extremely high. Recently identified risk factors for acquisition include prolonged hospitalization, prior antibiotic use, and serious underlying illness. Until effective therapy is available, prevention of infection by proper infection control procedures and judicious antibiotic use is critical.
Anti-Bacterial Agents↗
Effects of incubation time and buffer concentration on in vitro activities of antifungal agents against Candida albicans.
Nine selected isolates of Candida albicans were tested for their susceptibilities to amphotericin B and fluconazole by using three methods to assess the effect of incubation time and buffer concentration. By using a microdilution method with 0.0165 M 3-(N-morpholino)propanesulfonic acid (MOPS) and a 24-h incubation time, all of the isolates were found to be susceptible to amphotericin B and fluconazole. After 48 h of incubation, all isolates were still susceptible to amphotericin B. Seven of the nine isolates were resistant to fluconazole, and for the remaining two isolates, MICs increased by fourfold or more but the isolates remained susceptible (MIC, < or = 10 microg/ml). The nine isolates, along with three control strains, were further tested against amphotericin B and fluconazole by a standard broth macrodilution method with both 0.165 and 0.0165 M MOPS. The susceptibility results for fluconazole by the broth macrodilution method with the lower MOPS concentration correlated with the results of the 24-h broth microdilution method for determination of susceptibility or resistance in eight of nine tests and with the results of the 48 h broth microdilution method in three of nine tests. The results of the broth macrodilution method with the standard MOPS concentration did not correlate with any of the results obtained by the 24-h broth microdilution but correlated with results of seven of nine tests by the 48-h broth microdilution method. All nine test strains appeared to be susceptible when they were examined by a flow cytometric method. For clinical yeast susceptibility testing in microdilution panels, the 0.0165 M MOPS concentration combined with 24 h of incubation appeared to be the method of choice. The lower MOPS concentration may also be a useful modification to the tentative broth macrodilution method of the National Committee for Clinical Laboratory Standards. Use of the higher buffer concentration or longer incubation time may lead to false in vitro resistance for agents like fluconazole.
Amphotericin B↗
Hyperkalemia and trimethoprim-sulfamethoxazole.
Explore the source record for details and available documents.
Anti-Infective Agents↗
Selection of Enterococcus faecium strains with stable and unstable resistance to the streptogramin RP 59500 using stepwise in vitro exposure.
Therapy of vancomycin-resistant enterococcal infections is an increasing problem for many large medical centers. One promising agent for use against Enterococcus faecium is RP 59500 (Quinupristin/Dalfopristin). To assess the potential for emergence of resistant strains during clinical trials with this new compound, we collected and tested 11 vancomycin-resistant and three vancomycin-susceptible E. faecium strains. The strains were exposed to doubling dilutions of RP 59500, beginning at drug concentrations ranging from 0.25 to 16 micrograms/ml agar. A saturated swab with approximately 3 x 10(7) organisms/ml was spread as a lawn on agar containing RP 59500 and incubated at 35 degrees C for 48 h. Growth on the highest drug-containing plate was used to prepare the inoculum for the next series of resistance-selection experiments. After the final passage, the range of the highest RP 59500 plate concentration with growth was 32-512 micrograms/ml (initial resistance frequency ranging from 1 x 10(-6) to > 1 x 10(-4). After the selection of resistant strains, the organisms were passed twice weekly on antimicrobial agent-free media to determine resistance stability in the absence of drug. Resistance in strains with an RP 59500 MIC of > or = 16 micrograms/ml was stable after repeated passage for 4 weeks. These results indicate that stable resistance to RP 59500 can be selected in E. faecium when the organism is exposed to increasing drug concentrations only slightly above the minimum inhibitory concentration (MIC). This stable resistance is seen in strains exhibiting an MIC > or = 16 micrograms/ml, and unstable in those with resistance where the RP 59500 MIC is less than eight times the original drug MIC. Our observation suggests more than one mechanism of resistance is likely present when stable resistance to RP 59500 develops.
Anti-Bacterial Agents↗
Bacterial pneumonia associated with HIV-1 infection.
Bacterial pneumonia remains an important cause of treatable morbidity among HIV-1-infected persons. These pneumonias occur at all CD4 counts but are especially common as the HIV-1 infection progresses. Bronchopneumonia should be considered particularly in the setting of segmental or lobar consolidation associated with productive cough and fever. S. pneumoniae remains the most common pathogen causing bronchopneumonia. Because of the high rate of bacteremia, diagnosis may be facilitated by blood cultures. Treatment is similar to management of HIV-1-seronegative persons, although drug resistance against some bacteria may be an emerging problem. Several opportunities exist for prevention, and these should be pursued vigorously.
AIDS-Related Opportunistic Infections↗
Microbial contamination of blood conservation devices during routine use in the critical care setting: results of a prospective, randomized trial.
OBJECTIVES: To compare microbial contamination of two different blood conservation devices; to determine if there was an association between contamination of the blood conservation devices and clinical infections; to determine if there was a significant user preference for either of the two devices. DESIGN: Prospective, randomized trial. SETTING: Medical, neurosurgical, and spinal cord intensive care units of an urban, university hospital. PATIENTS: Forty patients who required clinically indicated intrafierial catheters placed at new sites. INTERVENTIONS: The two most widely available blood conservation devices at the time of the study (Venous Arterial blood Management Protection system [VAMP], Baxter Edwards Critical-Care, Irvine, CA; and Safe Draw, Ohmeda, Madison, WI) were chosen for comparison. After the normal 48 to 72 hrs of device use, the blood conservation systems were removed and semi-quantitative and quantitative cultures were taken from comparable sites of the two devices. Positive cultures from the patients were recorded and correlated with cultures obtained from the devices. In order to assess preference for either device, a survey tool was administered to the nursing staff who participated in the study. MEASUREMENTS AND MAIN RESULTS: Quantitative cultures from all sites cultured in both groups demonstrated mean colony counts of < 10(3) colony-forming units (cfu)/mL. There were no statistically significant differences in the colony counts at any of the sites compared between the two groups. There were no statistically significant relationships between positive cultures and patient age, gender, duration of device utilization, frequency of device entry, or the intensive care unit in which the study was conducted. In no circumstance did positive cultures from any of the blood conservation devices correlate with positive culture results from any sites of clinical infection. The clinical survey demonstrated a statistically significant preference for the VAMP system, which persisted despite increased experience with the Safe Draw system. CONCLUSIONS: The levels of microbial contamination noted in these devices were not consistent with clinical infection (defined as 10(3) cfu/mL on quantitative cultures). There was no significant difference in degree or pattern of contamination between the two devices. When utilized and changed according to the Centers for Disease Control guidelines, blood conservation devices are not harbors of infection in the critical care setting. Blood conservation devices can be used as part of a comprehensive blood conservation program in the critical care setting without undue concern for exacerbating infectious processes.
Blood Specimen Collection↗