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.     

High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity

BACKGROUND: Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 microg/mL. METHODS: A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>/=2 vs <2 microg/mL) for efficacy and high vs low trough (>/=15 vs <15 microg/mL) for nephrotoxicity analyses. RESULTS: Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents. CONCLUSIONS: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 microg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.     

Recurrent Staphylococcus aureus bacteremia: pulsed-field gel electrophoresis findings in 29 patients

To identify risk factors for relapse among 309 prospectively identified cases of Staphylococcus aureus bacteremia, patients with recurrent S. aureus bacteremia were identified, and pulsed-field gel electrophoresis (PFGE) was performed on isolates from both episodes. PFGE banding patterns from both isolates were identical in 23 patients, consistent with relapsed infection. Patients with PFGE-confirmed relapse were more likely by both univariate and multivariate analyses to have an indwelling foreign body (odds ratio [OR]=18.2, 95% confidence interval [CI]=7. 6-43.6; P<.001), to have received vancomycin therapy (OR=4.1, 95% CI=1.5-11.6; P=.008), or be hemodialysis-dependent (OR=4.1, 95% CI=1. 8-9.3; P=.002) than patients who did not develop recurrent bacteremia. These results suggest that recurrent episodes of S. aureus bacteremia are primarily relapses and are associated with an indwelling foreign body, receiving vancomycin therapy, and hemodialysis dependence.     

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.     

Evidence for a continuum of decreased vancomycin susceptibility in unselected Staphylococcus aureus clinical isolates

Some Staphylococcus aureus isolates have glycopeptide minimal inhibitory concentrations (MICs) in the susceptible range but have subpopulations that grow on >or=4 microg/mL vancomycin. Clinical laboratory methods for determining susceptibility have proven to be inadequate for detecting these strains. Among methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) clinical isolates, 149 (66.2%) of 225 and 17 (56.6%) of 30, respectively, grew on brain-heart infusion (BHI) medium containing 2 microg/mL vancomycin; 17 (7.5%) of the MRSA and 2 (6.6%) of the MSSA isolates grew on BHI screening plates containing 4 microg/mL vancomycin. One isolate grew on plates containing 6 microg/mL vancomycin. This isolate escaped detection by routine testing but had a vancomycin MIC of 6 microg/mL when tested in BHI medium. This isolate also had decreased Triton X-100-induced autolysis and killing when incubated in broth media containing vancomycin, properties accorded to glycopeptide-intermediate S. aureus isolates. These observations suggest that glycopeptide-intermediate-like S. aureus isolates are circulating undetected and that a continuum of decreased susceptibility exists in unselected isolates.     

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.     

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: 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.     

Treatment outcomes in patients with third-generation cephalosporin-resistant Enterobacter bacteremia

Abstract Background: Infections with resistant Enterobacter spp. are increasingly described, yet data on outcomes associated with these infections are limited. Methods: A retrospective cohort study was conducted to investigate outcomes of hospitalized patients with third-generation cephalosporin-resistant (CR) Enterobacter bacteremia. Cephalosporin resistance was detected using cefotaxime and cefpodoxime. Patients with Enterobacter spp. bacteremia from January 2006 through February 2008 defined the population. We defined cases as those with CR isolates; controls were patients with bacteremia due to non-CR isolates. Treatment failure was defined as persistence of the presenting signs of infection 72 h after initial culture collection. Results: Of the 95 Enterobacter cases identified, 31 (33%) were CR. CR cases were significantly associated with treatment failure (odds ratio (OR) 2.81, 95% confidence interval (CI) 1.14-6.94). This association was not seen after adjustment for age, simplified acute physiology score (SAPS II), and inappropriate empiric antibiotic therapy. Inappropriate empiric therapy (adjusted OR 3.86, 95% CI 1.32-11.31) and SAPS II score (adjusted OR 1.09, 95% CI 1.02-1.16) were significantly associated with treatment failure in the multivariate analysis. Conclusions: Third-generation cephalosporin-resistant Enterobacter bacteremia is associated with treatment failure due to receipt of inappropriate empiric antibiotic therapy and severity of illness.     

Impact of Prior Healthcare-Associated Exposure on Clinical and Molecular Characterization of Methicillin-Susceptible Staphylococcus aureus Bacteremia: Results From a Retrospective Cohort Study

By virtue of medical advances and an aging society, people have increased opportunities for healthcare exposure. Little is known about the impact of healthcare exposure on the clinical features and molecular typing of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We classified the onset of MSSA bacteremia into 3 mutually exclusive categories according to the Centers for Disease Control definition, and conducted a retrospective cohort study to investigate the differences among patients with community-associated (CA), healthcare-associated community onset (HACO), and hospital onset (HO) MSSA bacteremia at a medical center from January 1, 2002 through December 31, 2011. Antibiotic susceptibilities and multilocus sequence typing of MSSA isolates were also determined.A total of 290 patients with MSSA bacteremia, including of 165 (56.9%), 91 (31.4%), and 34 (11.7%) of HACO, HO, and CA, respectively, were studied. ST188 (29.3%) was the most common sequence type regardless of classification. Patients with HACO bacteremia were significantly older, had more solid tumors, higher Charlson scores, and more catheter-related bloodstream infections than those with CA bacteremia. The proportions of osteoarticular infections among patients with both HACO and CA bacteremia were higher than that of patients with HO bacteremia. By univariate analysis, patients with HO bacteremia had significantly higher in-hospital mortality compared to those with CA or HACO bacteremia (31.9% vs 18.8% and 20.4%). Multivariate analysis showed that Charlson score (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.10–1.52), septic shock (OR, 5.28; 95% CI, 2.37–11.78), liver cirrhosis (OR, 3.57; 95% CI, 1.14–11.24), receipt of β-lactams other than oxacillin and cefazolin as definitive therapy (OR, 9.27; 95% CI, 4.25–20.23), and higher oxacillin minimum inhibitory concentration (MIC) (≥0.5 mg/L) (OR, 2.35; 95% CI, 1.05–5.25) of the causative pathogen were independently associated with in-hospital mortality.In conclusion, patients with HACO bacteremia had different host factors compared with those with CA bacteremia. Infection foci varied with different onset settings. Overall, ST188 was the most predominant sequence type. Onset settings were not independently associated with outcomes.     

Clinical diagnostic accuracy of suspected sources of bacteremia and its effect on mortality

BackgroundAlthough much has been written about bacteremia, evidence of the clinical diagnostic accuracy of bacteremia sources in the absence of microbiological results and the impact of diagnostic accuracy on mortality is scarce.MethodsThis is a retrospective study of bacteremia episodes over a 2-year period at a general hospital in Madrid. Congruence analyses between clinically presumed and definite sources, acquisition, causative organism, empirical treatment and progression to death were performed.ResultsThe study included 323 bacteremia episodes. Clinicians' diagnostic accuracy was higher for gastrointestinal (88.8%; 95% CI: 79%–84%), respiratory (93.9%; 95% CI: 79%–99%) and urinary tract sources (83.6%; 95% CI: 75%–89%) and lower for skin and soft tissues (77.2%; 95% CI: 54%–92%) and, notably, intravascular sources (56%; 95% CI: 39%–71%).Overall, a non-significant (3.45%; 95% CI: ? 0.6%–13.5%, p = 0.47) increase in mortality was observed in the incorrectly suspected bacteremia source group.Mortality related to a definitive source was significantly higher when an intravascular origin was not suspected, resulting in a 26% increase in mortality (95% CI: 1%–52%, p = 0.03). Differences in mortality related to inaccurate source assumptions were non-significant when the definitive bacteremia sources were gastrointestinal, urinary, respiratory, skin and soft tissues or unknown.Mortality in the group receiving appropriate empirical antimicrobial treatment was 10.6% compared with 19.7% mortality in the group receiving inappropriate empirical antimicrobial treatment (OR 2; 95% CI: 1.01–4.25).ConclusionsThe diagnostic accuracy of bacteremia sources is high in all but intravascular sources. A non-suspected intravascular source and inappropriate empirical treatment are related to a higher mortality.     

Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia.

To assess whether methicillin resistance is a microbial characteristic associated with deleterious clinical outcome, we performed a cohort study on 908 consecutive episodes of Staphylococcus aureus bacteremia and a case-control study involving 163 pairs of patients matched for preexisting comorbidities, prognosis of the underlying disease, length of hospitalization, and age. Of 908 bacteremic episodes, 225 (24.8%) were due to methicillin-resistant S. aureus (MRSA). Multivariate analysis did not reveal that methicillin resistance was an independent predictor for mortality when shock, source of bacteremia, presence of an ultimately or rapidly fatal underlying disease, acquisition of the infection in an intensive care unit (ICU), inappropriate empirical therapy, female sex, and age were taken into account. Nonetheless, methicillin resistance was an independent predictor for shock. The case-control study could not confirm that shock was linked to MRSA when prior antimicrobial therapy, inappropriate treatment, ICU residence, and female sex were considered. Our data suggest that cohort studies tend to magnify the relationship of MRSA with clinical markers of microbial pathogenicity and that this effect is a shortcoming of these kind of studies that is caused by inadequate control for underlying diseases.     

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.     

Appropriate empirical antibiotic use and 30-d mortality in cirrhotic patients with bacteremia

AIM: To analyze whether prompt and appropriate empirical antibiotic(AEA) use is associated with mortality in cirrhotic patients with bacteremia. METHODS: A total of 102 episodes of bacteremia in 72 patients with cirrhosis were analyzed. AEA was defined as a using or starting an antibiotic appropriate to the isolated pathogen at the time of bacteremia. The primary endpoint was 30-d mortality. RESULTS: The mortality rate at 30 d was 30.4%(31/102 episodes). Use of AEA was associated with better survival at 30 d(76.5% vs 46.9%, P = 0.05), and inappropriate empirical antibiotic(IEA) use was an independent factor associated with increased mortality(OR = 3.24; 95%CI: 1.50-7.00; P = 0.003, adjusted for age, sex, ChildPugh Class, gastrointestinal bleeding, presence of septic shock). IEA use was more frequent when the isolated pathogen was a multiresistant pathogen, and when infection was healthcare-related or hospital-acquired. CONCLUSION: AEA use was associated with increased survival of cirrhotic patients who developed bacteremia. Strategies for AEA use, tailored according to the local epidemiological patterns, are needed to improve survival of cirrhotic patients with bacteremia.     

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.     

Risk factors for vancomycin-resistant Enterococcus faecalis bacteremia in hospitalized patients: an analysis of two case-control studies

BACKGROUND: Vancomycin-resistant enterococci (VRE) is an important pathogen in the hospital environment, and a progressive increase in its incidence is a cause of nosocomial infections. Bacteremia is one of the major infections caused by this pathogen. Risk factors for VRE bacteremia were assessed at a university-affiliated hospital. METHODS: Two case-control studies with different control groups were used. In study 1, patients with VRE bacteremia were compared with control patients matched by sex, admission unit, age (+/-10 years), and time of admission (+/-1 year). In study 2, the case group (VRE patients) was compared with vancomycin-susceptible enterococci (VSE) patients. RESULTS: A total of 34 patients with VRE bacteremia and 102 control patients were included in study 1, and 34 patients with VRE bacteremia and 55 patients with VSE bacteremia were included in study 2. In study 1, vancomycin use (OR, 10.19; CI 95%, 3.63-28.57) was associated with VRE bacteremia. In study 2, vancomycin use (OR, 17.58; CI 95%, 5.24-58.96) was also associated with VRE bacteremia. CONCLUSION: Because vancomycin use was the only variable associated with VRE bacteremia in the two studies, we confirmed that vancomycin exposure is the major risk factor for VRE 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.     

Tratamiento con daptomicina en pacientes con bacteriemia

Community-acquired bacteremias assciated with healthcare and, especially, those of nosocomial origin, are mainly caused by Gram-positive microorganisms. Notable among this group are Staphylococcus spp, with an incidence of methicillin resistance of approximately 30% in S. aureus and of 70% in coagulase-negative staphylococcus, which is higher in patients admitted to intensive care units. Vancomycin has been the most widely used antibiotic in these situations but its toxicity, especially in the kidney, and reports of failure when used for the treatment of methicillin-resistant S. aureus (MRSA) and with a vancomycin MIC > 1 mg/L have led to the search for other treatments.Daptomycin is a new lipopeptide antibiotic that has been shown to be not inferior to vancomycin in a pivotal clinical trial in patients with bacteremia and right endocarditis due to S. aureus. Recent guidelines and consensus documents place daptomycin as an ideal alternative in these situations, indicating its use in MRSA bacteremia with a vancomycin MIC > 1 mg/L, as well as in patients whose renal dysfunction excludes the use of vancomycin therapy. Evidence of worse prognosis in MRSA bacteremia when empirical treatment is inappropriate has led to the recommendation of daptomycin as the first-choice drug in critically ill patients with suspected Gram-positive bacteremic infection and renal dysfunction and/or in hospitals where there is a high prevalence of MRSA with a MIC > 1 mg/L. The recommended dose in severely ill patients should be higher than 6 mg/kg/day.     

Distribution of resistant gram-positive organisms across the census regions of the United States and in vitro activity of tigecycline, a new glycylcycline antimicrobial

BACKGROUND: Gram-positive isolates were collected from 76 medical centers within the 9 census regions across the United States. METHODS: Antimicrobial susceptibilities were determined according to Clinical and Laboratory Standards Institute guidelines. RESULTS: Vancomycin resistance among Enterococcus faecium isolates varied from 45.5% (New England) to 85.3% (East South Central). The lowest concentrations at which 90% of the isolates were inhibited (MIC90) were for tigecycline (0.06-0.12 microg/mL) and for linezolid (2-4 microg/mL). Methicillin-resistant Staphylococcus aureus (MRSA) varied from 27.4% (New England) to 62.4% (East South Central). All MRSA were susceptible to tigecycline, linezolid, and vancomycin. Penicillin-nonsusceptible Streptococcus pneumoniae ranged from 23.3% in the Pacific region to 54.5% in the East South Central region. Tigecycline, imipenem, levofloxacin, linezolid, and vancomycin all maintained MIC90 of < or =1 microg/mL against penicillin-nonsusceptible S pneumoniae in vitro, irrespective of region. CONCLUSION: This study demonstrates the variable rate of antimicrobial-resistant gram-positive organisms in the United States. Tigecycline may make a useful addition to the antimicrobial armamentarium.     

Risk factors for mortality due to bacteremia and fungemia in childhood.

To define risk factors for mortality due to bacteremia and fungemia of childhood, 242 episodes (for which the mortality rate was 19%) were studied prospectively by univariate and multivariate analyses. The mortality rate was higher in neonates (23%) and in individuals 10-18 years old (26%) than in infants and young children (10%-16%). The mortality rate was 29% for children who had neutropenia, 29% for those who had received therapy with steroids, 26% for those who had received antibiotics, and 75% for those who were in septic shock. The fatality rates for polymicrobial bacteremia (40%), recurrent bacteremia (67%), and hospital-acquired bacteremia (28%) were higher than those for other types of bacteremia; the fatality rate was related to inappropriate empiric antibiotic treatment or to the specific organism isolated (mortality rates associated with the latter ranged from 0 to 60%). Seven variables that independently and significantly affected mortality were defined with use of multivariate logistic regression analysis: septic shock (odds ratio [OR], 26.4); polymicrobial (OR, 5.4), recurrent (OR, 4.5), or hospital-acquired (OR, 4.3) bacteremia; candidemia (OR, 3.6); inappropriate antibiotic treatment (OR, 2.4); and neutropenia (OR, 2.3). These variables should be considered for adequate management of bacteremic patients who are at high risk for death.