Risk factors for methicillin-resistance among patients with Staphylococcus aureus bacteremia at the time of hospital admission

BACKGROUND: Community-acquired infections caused by methicillin-resistant Staphylococcus aureus (MRSA) seem to be increasing. Characteristics permitting recognition of patients with such strains would aid infection control efforts and choice of empiric therapy pending culture and susceptibility results. METHODS: Retrospective review of medical records for all adults seen in the Emergency Care Center at Grady Memorial Hospital, Atlanta, Georgia, whose blood cultures taken within 24 hours of entry yielded S. aureus. Risk factors for the presence of methicillin resistance in S. aureus isolates recovered from patients with staphylococcal bacteremia were assessed. RESULTS: S. aureus isolates from 118 (40%) of 297 study patients with bacteremia at the time of admission were methicillin-resistant. Multivariate analysis identified hospitalization in the 6 months preceding admission [odds ratio (OR) = 4.4; 95% CI, 2.0-9.8], receipt of antimicrobial agents in the past 3 months (OR = 5.6; 95% CI, 2.6-11.9], presence of indwelling urinary catheter (OR = 7.3; CI, 2.5-20.9), and nursing home residence (OR = 9.9; 95% CI, 3.9-25.6) to be independently associated with the presence of methicillin resistance. All but 4 of the 118 patients with methicillin-resistant strains had at least 1 of these factors and the proportion of resistant isolates progressively increased as more of these features were present. CONCLUSIONS: The presence of these risk factors should be considered when making decisions about isolation and other infection control procedures as well as empiric antimicrobial therapy with vancomycin for patients with suspected staphylococcal infection at the time of hospital admission. Similar studies could guide practices for dealing with such patients in other centers, because the occurrence of MRSA infections at the time of admission may vary widely by geographic area.     

Persistent Staphylococcus aureus bacteremia: an analysis of risk factors and outcomes

BACKGROUND: Persistent Staphylococcus aureus bacteremia (pSAB) is an emerging problem among hospitalized patients. We studied key clinical characteristics and outcomes associated with pSAB to better define the epidemiological features of this increasingly recognized clinical entity. METHODS: A retrospective case-control study of patients hospitalized with SAB between January 1, 2001, and September 30, 2004, was conducted to compare the clinical characteristics, management, and outcomes of patients with pSAB (> 7 days of bacteremia) with those of a cohort of patients with nonpersistent SAB (< 3 days of bacteremia). Patients with 4 to 6 days of bacteremia were excluded from the analysis. To detect a potential association between reduced susceptibility to vancomycin and persistent methicillin-resistant SAB, vancomycin susceptibilities were confirmed using standard dilution methods. RESULTS: Eighty-four patients with pSAB and 152 patients with nonpersistent SAB were included in the analysis. Methicillin resistance (odds ratio [OR], 5.22; 95% confidence interval [CI], 2.63-10.38), intravascular catheter or other foreign body use (OR, 2.37; 95% CI, 1.11-3.96), chronic renal failure (OR, 2.08; 95% CI, 1.09-3.96), more than 2 sites of infection (OR, 3.31; 95% CI, 1.17-9.38), and infective endocarditis (OR, 10.30; 95% CI, 2.98-35.64) were independently associated with pSAB. The mean time to device removal was significantly longer in patients with pSAB than in patients with nonpersistent SAB (4.94 vs 1.64 days; P < .01). There was no evidence of reduced vancomycin susceptibility among persistent methicillin-resistant S aureus isolates. Clinical outcomes were significantly worse among patients with pSAB. CONCLUSIONS: Many hospitalized patients may be at risk for pSAB. Aggressive attempts to minimize the risk of complications and poor outcomes associated with pSAB, such as early device removal, should be encouraged.     

Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia.

BACKGROUND: Vancomycin treatment failure in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is not uncommon, even when MRSA is susceptible to vancomycin. The aim of our study was to evaluate whether vancomycin minimum inhibitory concentration has any influence on the mortality associated with MRSA bacteremia. METHODS: A total of 414 episodes of MRSA bacteremia were prospectively followed-up from 1991 through 2005. MIC of vancomycin for the first isolate was determined by E-test. Clinical variables recorded were age, comorbidity, prior administration of vancomycin, use of corticosteroids, prognosis of underlying disease, source of bacteremia, the need for mechanical ventilation, shock, and mortality. A "treatment group" variable was created and defined as follows: (1) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1 microg/mL (38 episodes), (2) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1.5 microg/mL (90 episodes), (3) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (40 episodes), and (4) receipt of inappropriate empirical therapy (246 episodes). Univariate and multivariate analyses were performed. RESULTS: Episodes caused by strains with a vancomycin MIC of 2 microg/mL were independently associated with a lower risk of shock (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.15-0.75). Multivariate analysis selected receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (OR, 6.39; 95% CI, 1.68-24.3), receipt of inappropriate empirical therapy (OR, 3.62; 95% CI, 1.20-10.9), increasing age (OR, 1.02; 95% CI, 1.00-1.04), use of corticosteroids (OR, 1.85; 95% CI, 1.04-3.29), an ultimately (OR, 10.2; 95% CI, 2.85-36.8) or rapidly (OR, 1.81; 95% CI, 1.06-3.10) fatal underlying disease, high-risk (OR, 3.60; 95% CI, 1.89-6.88) and intermediate-risk (OR, 2.18; 95% CI, 1.17-4.04) sources of bacteremia, and shock (OR, 7.38; 95% CI, 4.11-13.3) as the best predictors of mortality. CONCLUSIONS: Mortality associated with MRSA bacteremia was significantly higher when the empirical antibiotic was inappropriate and when vancomycin was empirically used for treatment of infection with strains with a high vancomycin MIC (>1 microg/mL).     

Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study

Staphylococcus aureus bacteremia is associated with substantial morbidity. Recurrence is common, but incidence and risk factors for recurrence are uncertain. The emergence of methicillin resistance and the ease of administering vancomycin, especially in patients who have renal insufficiency, have led to reliance on this drug with the assumption that it is as effective as beta-lactam antibiotics, an assumption that remains open to debate.We initiated a multicenter, prospective observational study in 6 university hospitals and enrolled 505 consecutive patients with S. aureus bacteremia. All patients were monitored for 6 months and patients with endocarditis were followed for 3 years. Recurrence was defined as return of S. aureus bacteremia after documentation of negative blood cultures and/or clinical improvement after completing a course of antistaphylococcal antibiotic therapy. All blood isolates taken from patients with recurrent bacteremia underwent pulsed-field gel electrophoresis testing. Recurrence was subclassified as reinfection (different pulsed-field gel electrophoresis patterns) or relapse (same pulsed-field gel electrophoresis pattern).Forty-two patients experienced 56 episodes of recurrence (79% were relapses and 21% were reinfection). Relapse occurred earlier than reinfection (median, 36 versus 99 d, p < 0.06). Risk factors for relapse of S. aureus bacteremia included valvular heart disease, cirrhosis of the liver, and deep-seated infection (including endocarditis). Nafcillin was superior to vancomycin in preventing bacteriologic failure (persistent bacteremia or relapse) for methicillin-susceptible S. aureus (MSSA) bacteremia. Failure to remove infected intravascular devices/catheters and vancomycin therapy were common factors in patients experiencing multiple (greater than 2) relapses. However, by multivariate analysis, only endocarditis and therapy with vancomycin (versus nafcillin) were significantly associated with relapse.Recurrences occurred in 9.4% of S. aureus bacteremias following antistaphylococcal therapy, and most were relapses. Duration of antistaphylococcal therapy was not associated with relapse, but type of antibiotic therapy was. Nafcillin was superior to vancomycin in efficacy in patients with MSSA bacteremia.     

Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. a prospective multicenter study

BACKGROUND: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. DESIGN: Prospective observational study. SETTING: Four academic medical centers and a community hospital. PATIENTS: All patients with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.     

Persistent Staphylococcus aureus Bacteremia: A Prospective Analysis of Risk Factors,Outcomes, and Microbiologic and Genotypic Characteristics of Isolates

Persistent Staphylococcus aureus bacteremia (SAB) that fails to respond to appropriate antibiotic therapy is associated with poor outcomes. Comprehensive prospective studies on risk factors and outcomes of persistent bacteremia are limited. We investigated outcomes and risk factors encompassing clinical, pharmacokinetic, microbiologic, and genotypic characteristics associated with persistent bacteremia using a case-control study nested in a prospective cohort of patients with SAB at a tertiary-care hospital from August 2008 through September 2010. We compared the clinical characteristics, management, and outcomes of patients with persistent bacteremia (≥7 d) with controls with resolving bacteremia (<3 d). To detect associations between microbiologic and genotypic characteristics of methicillin-resistant S. aureus (MRSA) isolates and persistent bacteremia, we determined the heteroresistance phenotype, SCCmec type, agr genotype and functionality, multilocus sequence typing, and presence of 41 virulence genes. Our cohort consisted of 483 patients; 76 (15.7%) had persistent bacteremia, 212 (43.5%) had resolving bacteremia. In the multivariate analysis, independent risk factors associated with persistent bacteremia were community-onset bacteremia (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.24–6.87), bone and joint infection (OR, 5.26; 95% CI, 1.45–19.03), central venous catheter-related infection (OR, 3.36; 95% CI, 1.47–7.65), metastatic infection (OR, 36.22; 95% CI, 12.71–103.23), and methicillin resistance (OR, 16.99; 95% CI, 5.53–52.15). For patients with eradicable foci, delay (>3 d) in the removal of the infection focus was significantly associated with persistent bacteremia (OR, 2.18; 95% CI, 1.05–4.55). There were no significant associations of persistent bacteremia with high vancomycin minimal inhibitory concentration, vancomycin heteroresistance, and microbiologic/genotypic characteristics of MRSA isolates. However, initial vancomycin trough level <15 mg/L was an independent risk factor for persistent MRSA bacteremia (OR, 4.25; 95% CI, 1.51–11.96) in the multivariate analysis. Clinical outcomes were significantly worse for patients with persistent bacteremia. Relapse of bacteremia and attributable mortality within 12 weeks after SAB were significantly higher in patients with persistent bacteremia than in those with resolving bacteremia (9.2% [7/76] vs. 2.4% [5/212], p = 0.02 and 21.1% [16/76] vs. 9.4% [20/212], p = 0.009, respectively).In conclusion, patients with SAB should be given early aggressive treatment strategies, including early source control and maintenance of a vancomycin trough level ≥15 mg/L, to reduce the risk of persistent bacteremia.     

Staphylococcus aureus bacteremia: compliance with standard treatment, long-term outcome and predictors of relapse

The long-term outcome of compliance with standard treatment recommendations for Staphylococcus aureus bacteremia was assessed. Cases of S. aureus bacteremia at our institution over a 2-y period were reviewed and follow-up performed by review of subsequent admissions or contact with primary care physicians. We encountered 226 cases (age 64.7 +/- 15.8 y) and most (171/226, 75.7%) had no removable source. In-hospital mortality rate was 32.7% (74/226). Follow-up of 104/152 (68.4%) survivors (for 386.7 +/- 449.8 d) revealed 23.1% (24/104) relapses: recurrent bacteremia (n = 19), distant site (n = 3) and local recurrence (n = 2). Most relapses (21124; 87.5%) occurred within 90 d of therapy. Relapse rate was higher with vancomycin treatment (20148 vs. 4/56; p < 0.001), bacteremia for > or = 3 d (9/20 vs. 15/84; p = 0.001), and failure to remove the source (6/7 vs. 6/22; p = 0.006). Vancomycin effect was independent of oxacillin susceptibility. Treatment for less than the standard 2-week duration among 19 patients with short duration of bacteremia (< 3 d) did not increase relapse rate (1/19; 5.3%). Duration of bacteremia, vancomycin therapy and failure to remove the source were predictors of relapse. Prospective studies are needed to determine if S. aureus bacteremias of short duration can be treated for 2 weeks or less, and define the optimal duration for prolonged bacteremia when vancomycin is used.     

Delayed peripheral venous catheter-related Staphylococcus aureus bacteremia: onset ≥ 24 hours after catheter removal

Peripheral venous catheter (PVC)-associated bacteremia usually develops during the indwelling period. We present a review of 14 patients who developed delayed onset Staphylococcus aureus bacteremia (D-SAB), 1-6 days after PVC removal, and compare them to 29 patients with early onset PVC-related S. aureus bacteremia (E-SAB). At the time of removal, the catheter site exhibited inflammation in 8 (57.1%) cases. At SAB onset, PVC site inflammation developed in all patients. Compared to E-SAB, patients with D-SAB were more often aged ≥ 65 y (71.4% vs. 34.5%; p = 0.03) and on corticosteroids (35.7% vs. 6.9%; p = 0.02). D-SAB was more complicated with persistent (> 3 days) bacteremia (42.9% vs. 13.8%; p = 0.04), metastatic infections (35.7% vs. 6.9%; p = 0.02), and slightly higher mortality (21.4% vs. 10.3%; p = 0.3). Logistic regression revealed that the predictors of D-SAB were corticosteroids (odds ratio (OR) 2.10, 95% confidence intervals (CI) 1.16-58.61) and age ≥ 65 y (OR 1.63, 95% CI 1.12-23.30). These patients may have impaired local/systemic defenses that lead to D-SAB, or a blunted host response with delayed recognition.     

Streptococcus pneumoniae bacteremia in patients with cancer: disease characteristics and outcomes in the era of escalating drug resistance (1998-2002)

In the current era of multidrug-resistant organisms, the clinical spectrum of Streptococcus pneumoniae infection remains unclear, especially in immunosuppressed patients with cancer. We sought to define the characteristics of pneumococcal bacteremia in patients who were receiving care at a comprehensive cancer center. All consecutive episodes of S. pneumoniae bacteremia between January 1998 and December 2002 were evaluated retrospectively. One hundred thirty-five episodes of pneumococcal bacteremia occurred in 122 patients. Sixty-three (52%) of 122 patients had hematologic malignancies; the others had solid tumors. The median Acute Physiology and Chronic Health Evaluation II score was 14 +/- 5. Twenty-four episodes (18%) occurred during neutropenia (<500 cells/microL). Sixty-five patients (53%) were receiving antineoplastic therapy, and 36 (30%) were receiving systemic corticosteroids. Twelve (41%) of 29 hematopoietic stem cell transplant (HSCT) recipients had received transplantation within 12 months of the infection diagnosis; 11 patients had graft-versus-host disease (chronic in 10). In 27 episodes (22%), S. pneumoniae bacteremia was considered as a breakthrough infection. Nine (56%) of 16 hospital-acquired episodes of S. pneumoniae bloodstream infection occurred in patients with profound neutropenia, whereas 15 (13%) of 119 episodes of community-acquired infection occurred during neutropenia (p < 0.0002). In 91 episodes (67%), patients had radiographic evidence of pneumonia. Infected catheters were associated with 21 episodes (16%). Forty-eight (36%) of 135 isolates were not susceptible to penicillin (minimum inhibitory concentration [MIC] > or = 2 microg/mL); 9 (7%) showed intermediate susceptibility to ceftriaxone (MIC >0.5 and <2.0 microg/mL). Nineteen patients (16%) died within 2 weeks of diagnosis; 18 deaths were attributed to systemic pneumococcal infection. Univariate analysis showed no significant increase in the risk of short-term death in patients with infection due to penicillin non-susceptible organisms (OR [odds ratio], 1.47; 95% confidence intervals [CI], 0.53-4.05; p < 0.46), initially discordant treatment (OR, 1.0; 95% CI, 0.62-665.4; p < 0.16), presence of pneumonia (OR, 1.19; 95% CI, 0.39-3.62; p < 0.76), neutropenia (OR, 1.0; 95% CI, 0.28-4.09; p < 0.92), systemic corticosteroid use (OR, 1.96; 95% CI, 0.69-5.60; p < 0.21), or antineoplastic therapy (OR, 1.45; 95% CI, 1.52-4.05; p < 0.47). Similarly, patients with hematologic cancers compared to those with solid cancers (OR, 1.0; 95% CI, 0.49-3.70; p < 0.56) and recipients of HSCT compared to those with no history of transplantation (OR, 1.0; 95% CI 0.59-12.71; p < 0.20) did not have a less favorable outcome. In conclusion, most pneumococcal bloodstream infections were community acquired, although hospital-acquired infections were common in neutropenic patients. It is noteworthy that initially discordant therapy, penicillin non-susceptible S. pneumoniae, and other conventional predictors of unfavorable outcome were not associated with increased mortality rates in these high-risk patients with cancer.     

Persistent Staphylococcus aureus bacteremia: incidence and outcome trends over time

Persistent Staphylococcus aureus bacteremia (SAB-P) is well known but poorly delineated due to unclear definition. We retrospectively studied 78 patients with SAB-P using a stringent definition (bacteremia for > or = 7 d), in a single teaching hospital, during 1 January 2002 to 30 June 2003 and 1 November 2005 to 31 December 2006 to determine whether the frequency, risk factors and outcome changed over time. SAB was encountered in 354 and 259 instances during the 2 periods, respectively. Patients' characteristics changed with increasing organ dysfunction score (2.9+/-1.7 vs 3.4+/-1.4; p <0.001), patients with invasive devices (27.7% vs 41.3%; p=0.001), hemodialysis dependence (19.2% vs 27.8%; p=0.04), MRSA (50.8% vs 64.5%; p=0.001), and vancomycin treatment (57.9% vs 67.2%; p=0.02). SAB-P frequency increased slightly (11.0% vs 15.1%). Risk (associated) factors for SAB-P (identified by logistic regression) were metastatic infection (OR=5.60; 95% CI 3.00 - 10.47), vancomycin treatment (OR=4.17; 95% CI 2.14 - 8.11), endovascular sources (OR=3.35; 95% CI 1.92 - 5.85) and diabetes (OR=2.14; 95% CI 1.26 - 3.64). SAB- and SAB-P-associated case-fatality did not change (23.2% vs 18.5% and 25.6 vs 30.8%, respectively). All survivors ultimately achieved clearance. These findings suggest that patients with SAB are changing over time. Additionally, SAB-P frequency is higher than previously reported. SAB-P rise is probably due to increasing SAB, MRSA, and patients at risk for complications. Innovative approaches should target novel treatment modalities and risk reduction.     

Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort.

We performed a retrospective study of a large cohort of patients who had episodes of Staphylococcus aureus bacteremia (SAB) from January 1995 through February 1999 at 1 medical center to identify predictors of 30-day mortality in SAB. Among 293 patients with episodes of SAB, 68 died (23.2%) within 30 days of onset. There was no significant difference in 30-day mortality associated with treatment with vancomycin, a beta-lactam, or a miscellaneous group of antimicrobial agents (P=.180). By logistic regression, an acute physiology score (a component of the acute physiology and chronic health evaluation [APACHE III]) >60 at onset of SAB was the most important predictor of 30-day mortality (odds ratio [OR], 15.7). Other significant predictors were lung (OR, 5.8) or unknown (OR, 4.1) focus of SAB, age > or =65 years (OR, 2.0), and diabetes mellitus (OR, 2.4). Future investigators of SAB should take into consideration acute severity of illness at onset as well as other factors when evaluating or comparing outcomes.     

Nosocomial sepsis associated with interleukin-2

STUDY OBJECTIVE: To determine the incidence, clinical magnitude, and risk factors for nosocomial bacteremia in patients given interleukin-2 with or without (+/-) lymphokine activated killer (LAK) cells for cancer immunotherapy. DESIGN: Cohort study. SETTING: Clinical study unit of tertiary medical center. PATIENTS: All patients entering the interleukin-2 +/- LAK cancer immunotherapy protocol during a 28-month period. Control groups were patients in a surgical intensive care unit, patients receiving total parenteral nutrition, and patients with solid tumors. MEASUREMENTS AND MAIN RESULTS: Twenty of 107 (19%) interleukin-2-treated patients developed sepsis; in 12 of these patients, sepsis was intravenous catheter-associated. The bacteremia rate among patients receiving total parenteral nutrition, in the surgical intensive care unit, or having solid tumors was 2.8%, 4.1%, and 1.9%, respectively. Staphylococcus aureus was the pathogen in 13 courses; Staphylococcus epidermidis, in 5; and Escherichia coli, in 2. Two patients died; three developed suppurative thrombophlebitis; one developed septic arthritis; one, septic arterial aneurysm; and one, peritonitis with probable meningitis. Colonization with S. aureus increased the risk of S. aureus bacteremia 6.3-fold (95% CI, 2.8 to 14.5; P less than 0.001); skin desquamation at the catheter site increased the relative risk 2.0-fold (95% CI, 1.3 to 3.1; P = 0.031). Both colonization with S. aureus and skin desquamation increased the relative risk of S. aureus bacteremia 14.5-fold (95% CI, 4.1 to 50.9; P less than 0.0001). CONCLUSIONS: Staphylococcal bacteremia is more frequent in patients receiving interleukin-2 therapy and is associated with substantial morbidity and toxic skin reactions.     

Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study

Glutathione S-transferases (GSTs) have been associated with outcome in human cancers treated with cytotoxic chemotherapy. In a case-control study, we investigated the association between polymorphisms within the GSTM1, GSTT1, and GSTP1 genes and risk of relapse in childhood acute lymphoblastic leukemia (ALL). Cases were relapsed patients. Controls were successfully treated patients with a minimum follow-up of 5 years. The null genotype (absence of both alleles) for GSTM1 or GSTT1 conferred a 2-fold (OR = 0.5, 95% CI = 0. 23-1.07, P =.078) and 2.8-fold (OR = 0.36, 95% CI = 0.13-0.99, P =. 048) reduction in risk of relapse, respectively, relative to the presence of the GSTM1 or GSTT1 gene. The GSTP1 Val(105)/Val(105) genotype showed a 3-fold decrease in risk of relapse (OR = 0.33, 95% CI = 0.09-1.23, P =.099) in comparison to the combined category of Ile(105)/Val(105) and Ile(105)/Ile(105 )genotypes. No particular associations with relapse were observed for the GSTP1 polymorphism at codon 114. The risk of relapse when having 1 of the low-risk genotypes (GSTM1 null, GSTT1 null, GSTP1 Val(105)/Val(105)) decreased 1.9-fold (OR = 0.53, 95% CI = 0.24-1.19, P =.123), and the risk when having 2 or 3 low-risk genotypes 3.5-fold (OR = 0.29, 95% CI = 0.06-1.37, P =.118), compared with individuals having no low-risk genotype (P for trend =.005). Our results suggest that polymorphisms within genes of the GST superfamily may be associated with risk of relapse in childhood ALL. (Blood. 2000;95:1222-1228)     

Persistent bacteremia due to methicillin-resistant Staphylococcus aureus infection is associated with agr dysfunction and low-level in vitro resistance to thrombin-induced platelet microbicidal protein

BACKGROUND: The causes of persistent bacteremia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) are poorly understood. This investigation examined potential associations between PB with key clinical features and several in vitro bacterial genotypic and phenotypic characteristics, in isolates from 1 institution. METHODS: Pulsed-field gel electrophoresis (PFGE) relatedness, thrombin-induced platelet microbicidal protein (tPMP)-susceptibility phenotype, accessory gene regulator (agr) genotype and functionality (via delta-lysin production), and autolysis phenotypes were assessed in MRSA isolates from the bloodstream of 21 prospectively identified patients with PB (blood cultures positive after > or =7 days of therapy) and of 18 patients with resolving bacteremia (RB) (sterile blood cultures within the first 2-4 days of therapy) due to MRSA. RESULTS: The 2 groups had comparable baseline characteristics but differed in their clinical courses (e.g., endocarditis was more frequent in patients with PB than in those with RB [43% vs. 0%, respectively; P=.0016]); isolates from patients with PB exhibited higher rates of (1) survival in vitro after exposure to tPMP (22.4+/-14.8% vs. 11.6+/-6.5%, respectively; P=.005); (2) defective delta-lysin production (71.4% vs. 38.9%, respectively; P=.057); (3) non-agr genotype II profile (100% vs. 77.8%, respectively; P=.037); and (4) overrepresentation of a specific PFGE genotype (85.7% vs. 44.4%, respectively; P=.015). CONCLUSIONS: Isolates from patients with PB differed from those in patients with RB, in several in vitro characteristics. Further studies will be necessary to define how these factors might affect clinical outcome.     

Association between resistance to vancomycin and death in cases of Enterococcus faecium bacteremia.

We conducted a retrospective cohort study to determine the association between resistance to vancomycin and mortality among hospitalized patients with Enterococcus faecium bacteremia. We compared outcomes for patients infected with vancomycin-resistant versus vancomycin-susceptible E. faecium among 69 patients with bacteremia defined according to the National Nosocomial Infections Surveillance system. The univariate odds ratio (OR) for death associated with vancomycin resistance was 2.1 (P=.172). After controlling for severity of illness, we found that vancomycin resistance was not associated with mortality (OR, 1.74; 95% confidence interval, 0.5-6.12; P=.39). Vancomycin resistance does not independently increase mortality among patients with E. faecium bacteremia.     

Iron overload is a major risk factor for severe infection after autologous stem cell transplantation: a study of 367 myeloma patients

We evaluated the risk factors for infection of 367 consecutive myeloma patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT). Examination of bone marrow iron stores (BMIS) prior to ASCT was used to evaluate body iron stores. Other variables included age, sex, active smoking, myeloma remission status, severity of mucositis and duration of severe neutropenia post-ASCT (<100 absolute neutrophils counts (ANC)/microl). Median age was 56 years; 61% of patients were males. 140 episodes of severe infections occurred in 116 patients, including bacteremia (73), pneumonia (40), severe colitis (25) and bacteremia with septic shock (two). The infection incidence per 1,000 days at risk was 45.2. Pre-ASCT risk factors for severe infection by univariate analysis were increased BMIS (OR=2.686; 95% CI 1.707-4.226; P<0.0001), smoking (OR=1.565; 95% CI 1.005-2.437; P=0.0474) and male gender (OR=1.624; 95% CI 1.019-2.589; P=0.0414). Increased BMIS (OR=2.716; 95% CI 1.720-4.287; P<0.0001) and smoking (OR=1.714; 95% CI 1.081-2.718; P=0.022) remained significant by multivariate analysis. Duration of ANC <100 micro/l (OR=1.129; 95% CI 1.039-1.226; P=0.0069 and OR=1.127; 95% CI 1.038-1.224; P=0.0045 by both univariate and multivariate analysis, respectively) was the only post-ASCT risk factor for infection. Increased pre-transplant BMIS and smoking are significant predictors of severe infection after myeloablative chemotherapy followed by ASCT in myeloma patients.     

Emergence of community-associated methicillin-resistant Staphylococcus aureus USA 300 clone as a cause of health care-associated infections among patients with prosthetic joint infections

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as an important cause of staphylococcal infections, but there have been little data on whether CA-MRSA causes health care-associated infections. METHODS: A case-control study was performed to identify risk factors for prosthetic joint infections (PJI). Antibiograms of isolates associated with PJI were reviewed. Molecular typing of available MRSA isolates was done using pulsed field gel electrophoresis (PFGE). Nares cultures of health care workers who provided care to those orthopedic patients were obtained. RESULTS: Over a 13-month period (January 2003-January 2004), 9.5% of patients with prosthetic hip (THA) or knee (TKA) joint surgery developed PJI (7 TKA and 2 THA). The mean time to development of PJI was 20 days. Five infections were caused by CA-MRSA and 3 by methicillin-susceptible S aureus; one was culture negative. All CA-MRSA isolates had identical antibiograms (resistant to beta-lactams and erythromycin; susceptible to clindamycin, trimethoprim-sulfamethoxazole, rifampin, gentamicin, levofloxacin, and vancomycin). Molecular typing of 2 available CA-MRSA isolates revealed that these were the USA300 clone; these isolates were PVL+ and carried SCCmec IV. CA-MRSA was not recovered from nares cultures from 31 health care workers. In multivariate analysis, TKA (OR, 8.1; 95% CI: 1.3-48.1) and surgery time >180 minutes (OR, 7.4; 95% CI: 1.4-39.6) were associated with PJI. CONCLUSION: We have demonstrated that the CA-MRSA USA300 clone is no longer just a cause of community-acquired infections but has also emerged as a cause of health care-associated infections, causing PJI at our institution.     

Predicting methicillin resistance and the effect of inadequate empiric therapy on survival in patients with Staphylococcus aureus bacteremia

BACKGROUND: The restriction of vancomycin hydrochloride use is recommended as a measure to decrease the emergence of vancomycin resistance in gram-positive organisms; however, vancomycin also is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections. If vancomycin use is restricted to patients with documented infections due to methicillin-resistant organisms, then patients with MRSA infections may not initially receive vancomycin. This study was performed to determine factors that predict MRSA bacteremia and if ineffective empiric antibiotic therapy increased the risk of death in patients with S aureus bacteremia. METHODS: We conducted a retrospective cohort study of all patients with clinically significant S aureus bacteremia (132 episodes in 128 patients) diagnosed between October 1, 1995, and January 1, 1998, at an urban acute care Veterans Affairs medical center (approximately 200 acute care beds) in Baltimore, Md. During the study period, vancomycin was a restricted antibiotic. Empiric use had to be approved by an attending physician specializing in infectious diseases. RESULTS: Compared with patients who had methicillin-sensitive S aureus bacteremia, patients with MRSA bacteremia were significantly older (70 vs 58 years; P<.01), more likely to have a history of MRSA (47% vs 6%; P<.01) and a nosocomial infection (76% vs 50%; P<.01), and less likely to use injection drugs (8% vs 32%; P<.01). In addition, compared with patients who had methicillin-sensitive S aureus bacteremia, patients with MRSA bacteremia were significantly less likely (45% vs 98%; P<.01) to receive effective antibiotic therapy during the first 48 hours of hospitalization. However, the risk of death due to ineffective empiric therapy was less than 1 (relative risk, 0.82; 95% confidence interval, 0.36-1.88) and did not change significantly when adjusted for age, occurrence of sepsis, or nosocomial infection. CONCLUSIONS: The results of this study support the safety of the restriction of vancomycin use in patients with clinically significant S aureus bacteremia. However, patients with a history of MRSA are more likely to have future MRSA infections and should receive empiric therapy using vancomycin for possible S aureus infections, particularly for nosocomial infections.     

Community-onset methicillin-resistant Staphylococcus aureus bacteremia in Northern Australia.

BACKGROUND: Community-onset infections caused by methicillin-resistant Staphylococcus aureus (COMRSA) are being increasingly reported worldwide. METHODS: A retrospective study was performed of 14 patients with 15 episodes of COMRSA bacteremia (COMRSAB) admitted to the Royal Darwin Hospital, Northern Territory, Australia from 1998 to 2001. Isolates from COMRSAB episodes underwent extended susceptibility testing and molecular typing by pulsed field gel electrophoresis and allotyping of the staphylococcal cassette chromosome mec (SCCmec) region by polymerase chain reaction. RESULTS: The proportion of community-onset S. aureus bacteremia episodes that were due to COMRSA increased from 9% in 1998 to 20% in 2001. The clinical features of COMRSAB were similar to those seen with methicillin-susceptible strains, including sepsis, endocarditis and metastatic infection. Ineffective empiric antimicrobial therapy was administered in the majority (80%) of episodes. All COMRSAB isolates tested contained allotype IV SCCmec, which is commonly found in community isolates of MRSA and rarely found in isolates from healthcare-associated MRSA infection. CONCLUSION: The increasing incidence of COMRSAB in our region has resulted in the addition of vancomycin to standard empiric therapy in certain patients with suspected S. aureus bacteremia acquired in the community.