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Biomedical subjects

M H Samore

Publications and source records attributed to M H Samore.

At least 37 records · Page 2Linked to original sources

Vancomycin-resistant enterococci in intensive care units: high frequency of stool carriage during a non-outbreak period.

BACKGROUND: We aimed to define the epidemiological associations of vancomycin-resistant enterococci (VRE) in intensive care units (ICUs) during a non-outbreak period by examining prevalence, risk factors for colonization, frequency of acquisition, and molecular strain types. DESIGN: A prospective cohort design was followed. Consecutive patient admissions to 2 surgical ICUs at a tertiary care hospital were enrolled. The main outcome measures were results of serial surveillance cultures screened for VRE. RESULTS: Of 290 patients enrolled, 35 (12%) had colonization with VRE on admission. The VRE colonization or infection had been previously detected by clinical cultures in only 4 of these patients. Using logistic regression, VRE colonization at the time of ICU admission was associated with second- and third-generation cephalosporins (odds ratio [OR] = 6.0, P<.0001), length of stay prior to surgical ICU admission (OR = 1.06, P = .001) greater than 1 prior ICU stay (OR = 9.6, P = .002), and a history of solid-organ transplantation (OR = 3.8, P = .021). Eleven (12.8%) of 78 patients with follow-up cultures acquired VRE. By pulsed-field gel electrophoresis, 2 strains predominated, one of which was associated with an overt outbreak on a non-ICU ward near the end of the study period. CONCLUSIONS: Colonization was common and usually not recognized by clinical culture. Most patients who had colonization with VRE and were on the surgical ICU acquired VRE prior to surgical ICU entry. Exposure to second- and third-generation cephalosporins, but not vancomycin, was an independent risk factor for colonization. Prospective surveillance of hospitalized patients may yield useful insights about the dissemination of nosocomial VRE beyond what is appreciated by clinical cultures alone.

Aged↗

Health and economic outcomes of antibiotic resistance in Pseudomonas aeruginosa.

BACKGROUND: Antimicrobial resistance is an increasing problem. OBJECTIVE: To examine the clinical and economic impact of antibiotic resistance in Pseudomonas aeruginosa. METHODS: In-hospital mortality, secondary bacteremia, length of stay, and hospital charges were examined in a cohort of 489 inpatients with positive clinical cultures for P aeruginosa. One hundred forty-four had a resistant baseline P aeruginosa isolate and 30 had resistance emerge during follow-up. Multivariable and survival analytic methods were used to adjust for confounding and effects of time. RESULTS: The overall in-hospital mortality rate was 7.6%, 7.7% in patients with a resistant isolate at baseline (relative risk [RR], 1.3; 95% confidence interval [CI], 0.6-2.8) and 27% in patients in whom resistance emerged (RR, 3.0; 95% CI, 1.2-7.8). Secondary bacteremia developed in 1.4% of patients in whom resistance did not emerge and in 14% of those in whom resistance emerged (RR, 9.0; 95% CI, 2.7-30). The median duration of hospital stay following the initial P aeruginosa isolate was 7 days. Emergence of resistance, but not baseline resistance, was significantly associated with a longer hospital stay (P<.001 and P=.71, respectively). The average daily hospital charge was $2059. Neither baseline resistance nor emergence of resistance had a significant effect on the daily hospital charge. In a matched cohort analysis, a trend was seen toward increased total charges in patients demonstrating emergence of resistance (difference, $7340; P=.14). CONCLUSIONS: Emergence of antibiotic resistance in P aeruginosa results in severe adverse outcomes. Efforts should be directed toward early detection and prevention of emergence of antibiotic resistance.

Adult↗

Epidemiology of nosocomial clostridium difficile diarrhoea.

Clostridium difficile is a frequent and clinically important cause of diarrhoea that has been strongly but not exclusively associated with the hospital setting. The vast majority of cases of C. difficile diarrhoea are associated with antecedent treatment with antibiotics, of which cephalosporins and clindamycin appear to pose the highest risk. Within hospitals and chronic-care facilities, cross-infection of C. difficile has been related to transient carriage on hands of healthcare workers and contamination of diverse environmental surfaces, including electronic rectal thermometers. Prospective epidemiologic studies have demonstrated that acquisition of C. difficile is common in hospitalized patients. Although colonized patients contribute to nosocomial transmission of C. difficile, symptom-free carriage of C. difficile appears to reduce risk of subsequent development of C. difficile diarrhoea. Antimicrobial treatment with oral metronidazole or vancomycin to attempt to eradicate symptomless carriage is not recommended. Measures to control nosocomial C. difficile diarrhoea have focused on improved handwashing, use of barrier precautions with single rooms for symptomatic patients, reduction of environmental contamination, and antibiotic restriction. Restricting clindamycin has been particularly successful in terminating outbreaks of C. difficile diarrhoea associated with its use. The epidemiologic features of C. difficile and strategies for control are similar to those for micro-organisms that have acquired antimicrobial resistance. C. difficile may be indirectly or directly contributing to spread of resistant organisms, for instance, by causing diarrhoea and thereby enhancing environmental contamination with other gastrointestinal flora such as vancomycin-resistant enterococci. Thus, a consideration of C. difficile in the larger context of the world-wide spread of antibiotic resistance offers useful insights that may help form the basis for the development of more effective control measures.

Cross Infection↗

Epidemiological analysis of imipenem-resistant Serratia marcescens in hospitalized patients.

Our objective was to examine epidemiological characteristics of hospitalized patients with imipenem-resistant Serratia marcescens. We performed a case-control study using data collected from computerized databases and chart review. Molecular typing by pulsed field gel electrophoresis of available isolates was performed. One hundred and ten patients had Serratia spp isolated during the 23-month study period. Twelve were infected or colonized with S. marcescens resistant or of intermediate susceptibility to imipenem. Eleven of the 12 patients were detected during a seven-month period between August 1994 and February 1995, suggesting the possible occurrence of an outbreak. However, the patients were admitted to different wards and services and, in eight patients, imipenem-resistant S. marcescens were isolated within 48 h or admission. None of the patients had epidemiological links within other institutions. The 12 cases were not more likely to have been exposed to beta-lactam antibiotics, including imipenem, than patients with imipenem-susceptible isolates. Six isolates were available for typing by PFGE; three were indistinguishable or closely related whereas each of the other three isolates were unique. In conclusion both the prevalence of imipenem-resistant S. marcescens and its unusual epidemiologic characteristics warrant further study.

Boston↗

A cluster of VanD vancomycin-resistant Enterococcus faecium: molecular characterization and clinical epidemiology.

VanD-mediated glycopeptide resistance has been reported for an isolate of Enterococcus faecium, BM4339. Three clinical isolates of vancomycin-resistant E. faecium collected from 3 patients during a 6-week period in 1993 had agar dilution MICs of vancomycin and teicoplanin of 128 and 4 microg/mL, respectively. Polymerase chain reaction (PCR) using degenerate primers complementary to genes encoding d-Ala-d-X ligases yielded a 630-bp product that was similar to the published partial sequence of vanD. By use of inverse PCR, vanD, vanHD, and two partial flanking open-reading frames were sequenced. The deduced amino acid sequence of VanD showed 67% identity with VanA and VanB. vanD appeared to be located on the chromosome and was not transferable to other enterococci. The 3 isolates were indistinguishable by pulsed-field gel electrophoresis and differed from BM4339. No other isolates carrying vanD were found in a subset of 875 recent US isolates of vancomycin-resistant enterococci.

Amino Acid Sequence↗

Risk factors for nosocomial candiduria due to Candida glabrata and Candida albicans.

The aims of this study were to analyze the clinical characteristics and risk factors associated with catheter-associated candiduria due to Candida glabrata and due to Candida albicans and to compare patients with candiduria due to C. glabrata or C. albicans (cases) with controls. Controls were a randomly chosen sample of inpatients with Foley catheters for whom urine cultures were negative for Candida species. Univariate and multivariate analyses were performed. There were 40 cases of C. glabrata candiduria and 289 cases of C. albicans candiduria. Factors strongly associated with both C. albicans candiduria and C. glabrata candiduria were female gender (P <. 05) and being in the intensive care unit (P <. 01). Fluconazole use (adjusted odds ratio, 4.37; P <. 01) and quinolone use (adjusted odds ratio, 3.16; P <. 01) were specifically associated with C. glabrata candiduria but not with C. albicans candiduria. In conclusion, patients receiving fluconazole treatment are at risk of developing C. glabrata candiduria.

Aged↗

Colonization with broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units during a nonoutbreak period: prevalence, risk factors, and rate of infection.

OBJECTIVE: To define the epidemiology of broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units (ICUs) during a nonoutbreak period, including the prevalence, the risk factors for colonization, the frequency of acquisition, and the rate of infection. DESIGN: Prospective cohort study. SETTING: Tertiary care hospital. PATIENTS: Consecutive patients admitted to two surgical ICUs. MAIN OUTCOME MEASUREMENTS: Serial patient surveillance cultures screened for ceftazidime (CAZ) resistance, antibiotic and hospital exposure, and infections. RESULTS: Of the 333 patients enrolled, 60 (18%) were colonized with CAZ-resistant gram-negative bacilli (CAZ-RGN) at admission. Clinical cultures detected CAZ-RGN in only 5% (3/60) of these patients. By using logistic regression, CAZ-RGN colonization was associated with duration of exposure to cefazolin (odds ratio, 10.3; p < or = .006) and to broad-spectrum cephalosporins/penicillins (odds ratio, 2; p < or = .03), Acute Physiology and Chronic Health Evaluation III score (odds ratio, 1.2; p < or = .008), and previous hospitalization (odds ratio, 3.1; p < or = .006). Of the 100 patients who remained in the surgical ICU for > or = 3 days, 26% acquired a CAZ-RGN. Of the 14 infections caused by CAZ-RGN, 11 (79%) were attributable to the same species present in surveillance cultures at admission to the surgical ICU. CONCLUSIONS: Colonization with CAZ-RGN was common and was usually not recognized by clinical cultures. Most patients colonized or infected with CAZ-RGN had positive surveillance cultures at the time of admission to the surgical ICU, suggesting that acquisition frequently occurred in other wards and institutions. Patients exposed to first-generation cephalosporins, as well as broad-spectrum cephalosporins/penicillins, were at high risk of colonization with CAZ-RGN. Empirical treatment of nosocomial gram-negative infections with broad-spectrum cephalosporins, especially in the critically ill patient, should be reconsidered.

Aged↗

Emergence of antibiotic-resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents.

Pseudomonas aeruginosa is a leading cause of nosocomial infections. The risk of emergence of antibiotic resistance may vary with different antibiotic treatments. To compare the risks of emergence of resistance associated with four antipseudomonal agents, ciprofloxacin, ceftazidime, imipenem, and piperacillin, we conducted a cohort study, assessing relative risks for emergence of resistant P. aeruginosa in patients treated with any of these drugs. A total of 271 patients (followed for 3,810 days) with infections due to P. aeruginosa were treated with the study agents. Resistance emerged in 28 patients (10.2%). Adjusted hazard ratios for the emergence of resistance were as follows: ceftazidime, 0.7 (P = 0.4); ciprofloxacin, 0.8 (P = 0.6); imipenem, 2.8 (P = 0.02); and piperacillin, 1.7 (P = 0.3). Hazard ratios for emergence of resistance to each individual agent associated with treatment with the same agent were as follows: ceftazidime, 0.8 (P = 0.7); ciprofloxacin, 9.2 (P = 0.04); imipenem, 44 (P = 0.001); and piperacillin, 5.2 (P = 0.01). We concluded that there were evident differences among antibiotics in the likelihood that their use would allow emergence of resistance in P. aeruginosa. Ceftazidime was associated with the lowest risk, and imipenem had the highest risk.

Adult↗

Phase I study of a human monoclonal antibody directed against the CD4-binding site of HIV type 1 glycoprotein 120.

A phase I dose escalation study was conducted with the human monoclonal anti-gp120 antibody F105, to evaluate the safety, pharmacokinetics, and functional activity of F105 in HIV-1-infected individuals. F105 is an IgG1(kappa) antibody reactive with a discontinuous epitope that overlaps the CD4-binding site of gp120. F105 neutralizes laboratory strains of HIV-1 and some primary isolates, and synergizes with other antibodies in neutralizing an expanded spectrum of isolates. Four patients each with CD4 counts between 200 and 500/mm3 received a single dose of F105 at 100 or 500 mg/m2, intravenously. Sustained levels of F105 were obtained in plasma, and there was no evidence of an immune response to F105 as determined by a double-antigen immunoassay. No patient experienced any toxicity. Infused antibody retained full functional activity as detected by the ability of sera to block the binding of labeled F105 to HIV-1-infected cells. Of note, all patients had preexisting antibody to the gp120 CD4-binding site. The ability to culture virus by quantitative microculture remained unchanged by this single dose of antibody. Thus, it can be concluded that F105 is safe and nontoxic as a single injection at the doses tested. Furthermore, the antibody retains full gp120-binding activity. In these patients, with preexisting CD4-binding site antibody, there is no evidence of anti-HIV-1 activity following a single antibody infusion.

Adult↗

Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea.

BACKGROUND: Little is known about whether patients who develop Clostridium-difficile-associated diarrhoea (CDAD) are culture-positive or culture-negative before illness. The most important risk factor is antibiotic exposure. We aimed to find out whether patients identified as primary symptom-free C difficile carriers are at higher risk of developing CDAD than patients who are culture-negative. METHOD: We reviewed four longitudinal studies in which 810 patients admitted to hospital were followed up by prospective rectal-swab culture. At least two consecutive weekly cultures were obtained. We calculated the difference in risk of CDAD between colonised and non-colonised patients in each study and combined the results of the four studies in a random-effects model. FINDINGS: Of 618 non-colonised patients (mean follow-up 1.7 weeks [SD 1.3]), 22 (3.6%) developed CDAD, whereas only two (1.0%) of 192 primary symptom-free carriers (1.5 [1.5]) developed CDAD (pooled risk difference -2.3% [95% CI 0.3-4.3], p=0.021). Of patients who received antibiotics, the risk difference was increased: 22 (4.5%) of 491 non-colonised patients compared with two (1.1%) of 176 colonised patients developed CDAD (-3.2% [0.4-6.0], p=0.024). Of the primary symptom-free C difficile carriers, 95 were colonised with toxigenic strains, 76 with non-toxigenic strains, 12 with both toxigenic and non-toxigenic strains (non-concurrently), and nine with strains of undetermined toxigenicity. Nine of the 12 toxogenic strains of C difficile isolates that cause CDAD were also recovered from stools of symptom-free patients. INTERPRETATION: Primary symptomless C difficile colonisation is associated with a decreased risk of CDAD. Although the mechanism is unknown, risk reduction is found in colonisation with non-toxigenic and toxigenic strains.

Adult↗

Stool colonization of healthcare workers with selected resistant bacteria.

We examined the carriage of selected resistant bacteria in the stools of healthcare workers who provided direct patient care. Neither vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, nor Clostridium difficile was recovered from the 55 stool specimens collected. A ceftazidime-resistant Citrobacter freundii was isolated from one specimen. We conclude that the stool of healthcare workers is colonized infrequently with these resistant organisms.

Adult↗

Carriage of methicillin-resistant Staphylococcus aureus at hospital admission.

OBJECTIVES: To measure the prevalence of, and to establish predictors for, the nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) at hospital admission. To evaluate mannitol-salt agar with oxacillin for the simultaneous detection and identification of MRSA from nasal swabs. DESIGN: Three-month prospective case-control survey, with data collected from interviews and computerized databases. The criterion standard for MRSA detection was culture on Mueller-Hinton agar with oxacillin 6 microg/mL (National Committee for Clinical Laboratory Standards method). SETTING: 320-bed tertiary-care hospital. PATIENTS: 387 patients screened within 24 hours after admission, including 10 MRSA carriers (cases), 291 patients with no S aureus, and 86 patients with methicillin-susceptible S aureus. RESULTS: The prevalence of MRSA nasal carriage was 2.6%, whereas the prevalence of carriage was 3.1% when both nasal and wound cultures were performed. The significant predictors of carriage were a prior detection of MRSA, open wounds, diabetes mellitus, treatments by injection, prior nursing home stays, visits at home by a nurse, and prior antibiotic treatments. Cases had stayed for longer periods in hospitals and had received longer antibiotic treatments within a year. Eighty patients (including the 10 cases) had diabetes, had been exposed to healthcare facilities within a year, and had antibiotics within 6 months. The sensitivity and negative predictive value of nasal swabs on mannitol-salt agar with oxacillin were 60% and 71%, respectively. CONCLUSION: MRSA carriage on admission to the hospital may be an increasing and underestimated problem. Further studies are needed to develop and validate a sensitive and specific prediction rule.

Adolescent↗

Diagnostic characteristics of cerebrospinal fluid analysis for secondary menigitis in HIV-infected adults.

BACKGROUND: When human immunodeficiency virus (HIV)-infected patients present with neurologic problems, lumbar puncture and cerebrospinal fluid (CSF) analysis are often performed, usually to rule-out the presence of meningitis. However, the test characteristics of CSF analyses in this population are unknown. METHODS: To examine the diagnostic characteristics of CSF analyses for secondary causes of meningitis in HIV-infected adults, we performed a case-control study of 322 HIV-infected adults who received diagnostic lumbar puncture in an urban academic hospital from 1989 to 1992. Using multivariable logistic regression analyses, we determined the independent CSF correlates of cryptococcal and other types of secondary meningitis. RESULTS: Eighty percent were men who had sex with men, 89% were white, and 85% had AIDS. Thirty-seven case-subjects had a secondary cause of meningitis though none had bacterial or tuberculous meningitis. Excluding the india ink as a candidate variable, logistic regression analysis identified 2 independent CSF correlates of secondary meningitis: the leukocyte count (odds ratio [OR] per 10 cells, 1.2; 95% confidence interval [CI], 1.1 to 1.3), and the CSF-to-serum glucose ratio (OR per 0.10 units, 0.61; CI, 0.43 to 0.88). The areas (+/- SD) under the receiver operating characteristic curves were 0.76 +/- 0.05 and 0.72 +/- 0.05, respectively. CONCLUSIONS: In similar clinical settings, these findings may help clinicians assess the probability of secondary meningitis in HIV-infected patients when initial CSF results first become available.

Adult↗

Frequency, risk factors, and outcome for bacteremia after percutaneous transluminal coronary angioplasty.

The objectives of this study were to examine bacteremias after percutaneous transluminal coronary angioplasty (PTCA) with respect to incidence, outcome, and risk factors. Patients undergoing PTCA from January 1990 through April 1994 were studied; during this period a total of 4,217 PTCAs were performed in 3,473 patients. With use of predefined clinical and microbiologic criteria, bacteremias were divided into 3 categories according to the relation to the PTCA procedure: PTCA-related, unrelated, and indeterminate. Ninety-one patients with at least 1 positive blood culture during a 7-week period after PTCA were identified. The bacteremia was classified as unrelated to the PTCA procedure in 32 patients, PTCA-related in 27, and indeterminant in the remaining 32 patients. The attack rate of PTCA-related bacteremia during the 52-month period was 0.64%. The most common organisms causing PTCA-related bacteremia were Staphylococcus aureus (14 patients), coagulase-negative staphylococci (9 patients) and group B streptococci (6 patients). Septic complications, which included femoral artery mycotic aneurysm, septic arthritis, and septic thrombosis, occurred in 10 patients (0.24%). Independent risk factors for PTCA-related bacteremia included duration of procedure (odds ratio [OR] 2.9; p = 0.04), number of catheterizations at the same site (OR 4.0; p = 0.015), difficult vascular access (OR 14.9; p = 0.007), arterial sheath in place > 1 day (OR 6.8; p = 0.025), congestive heart failure (OR 43.3; p = 0.002). Thus, PTCA-related bacteremia is an infrequent complication of PTCA but can be associated with significant morbidity, particularly when the infecting organism is S. aureus. Four of the 5 risk factors for PTCA-related bacteremia appear to correlate directly with increased vascular injury or maintenance of the arterial entry for the procedure.

Aged↗

Comparison of treatment with imipenem vs. ceftazidime as a predisposing factor for nosocomial acquisition of Stenotrophomonas maltophilia: a historical cohort study.

Imipenem is considered to confer greater risk for the acquisition of Stenotrophomonas maltophilia than are other beta-lactam antibiotics. We conducted a historical cohort study to directly compare the risks of S. maltophilia acquisition in patients treated with imipenem vs. ceftazidime during a 2-year period; 843 hospitalizations of 759 patients treated with ceftazidime (465 hospitalizations), imipenem (294), or both agents (84) were included. Acquisition, as measured by clinical detection, occurred in 24 hospitalizations. Rates of acquisition did not significantly differ between the imipenem and ceftazidime groups (3.7 vs. 7.1 cases per 10,000 patients days; P = .2). In contrast, patients treated with both agents had higher acquisition rates (19 cases per 10,000 patient days; P = .002). Thus, patients treated with imipenem are not at significantly higher risk for S. maltophilia acquisition than those treated with ceftazidime. The excessive risk for patients treated with both agents may be related in part to longer antibiotic therapy and a longer hospital stay.

Anti-Bacterial Agents↗

Imipenem-resistant Pseudomonas aeruginosa: risk factors and antibiotic susceptibility patterns.

Potential risk factors for the detection of imipenem-resistant Pseudomonas aeruginosa in hospitalized patients were assessed by a case-control study. Forty patients whose first P. aeruginosa isolate was resistant or intermediate to imipenem were more likely than 387 controls to have received imipenem (odds ratio [OR] = 16.9; P < .0001) and to have undergone organ transplantation (OR = 3.9; P = .008). No significant difference was found for treatments with other antibiotics, other underlying diseases, demographic characteristics, different exposures to the hospital environment, or the culture site. Imipenem-resistant P. aeruginosa isolates were more likely to be resistant to other common antipseudomonal agents than were imipenem-susceptible isolates. It is concluded that treatment with imipenem, but not with other beta-lactam drugs, is a major risk factor for the detection of imipenem-resistant P. aeruginosa in hospitalized patients, that these organisms may relatively often be resistant to other antipseudomonal agents, and that the hospital environment per se might not play a major role in their epidemiology.

Case-Control Studies↗

Diarrhea and quality of life in ambulatory HIV-infected patients.

Our objectives were to determine HIV-infected patients' awareness and recognition of diarrheal symptoms; and to assess the impact of diarrhea on quality of life. The design was a cross-sectional study utilizing a structured telephone interview. The setting was the HIV/AIDS outpatient clinic of a tertiary referral hospital. HIV-infected patients who attended the clinic in 1994 were interviewed. The main outcome measure was the quality-of-life score (QLS). Fifty percent of patients acknowledged having diarrhea in the previous month. All four categories of diarrhea (self-reported or elicited, within the preceding week or month) were significantly associated with decreased QLS. Patients with diarrhea who did not recognize their symptoms as diarrhea also had significantly lower QLS than patients without diarrhea. Diarrhea in all categories was independently predictive of decreased QLS by multivariable analysis. Chronic diarrhea (symptoms for more than one month) was significantly associated with decreased QLS in patients with high as well as low CD4 cell counts. Lack of recognition of diarrhea may result in significant underreporting of diarrhea by patients to physicians. Diarrhea is highly prevalent in the HIV-infected population and is strongly associated with diminished quality of life.

Acquired Immunodeficiency Syndrome↗