Inappropriate Empirical Antibiotic Therapy Research Articles

Risk Factors and Outcomes of Bacteremia Caused by Drug-Resistant ESKAPE Pathogens in Solid-Organ Transplant Recipients

Although infections due to the six ESKAPE pathogens have recently been identified as a serious emerging problem, information regarding bacteremia caused by these organisms in solid-organ transplant (SOT) recipients is lacking. We sought to determine the frequency, risk factors, and outcomes of bacteremia due to drug-resistant ESKAPE (rESKAPE) organisms in liver, kidney, and heart adult transplant recipients. All episodes of bacteremia prospectively documented in hospitalized SOT recipients from 2007 to 2012 were analyzed. Of 276 episodes of bacteremia, 54 (19.6%) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium [0], methicillin-resistant Staphylococcus aureus [5], extended-spectrum β-lactamase-producing Klebsiella pneumoniae [10], carbapenem-resistant Acinetobacter baumannii [8], carbapenem- and quinolone-resistant Pseudomonas aeruginosa [26], and derepressed chromosomal β-lactam and extended-spectrum β-lactamase-producing Enterobacter species [5]). Factors independently associated with rESKAPE bacteremia were prior transplantation, septic shock, and prior antibiotic therapy. Patients with rESKAPE bacteremia more often received inappropriate empirical antibiotic therapy than the others (41% vs. 21.6%; P=0.01). Overall case-fatality rate (30 days) was higher in patients with rESKAPE bacteremia (35.2% vs. 14.4%; P=0.001). Bacteremia due to rESKAPE pathogens is frequent in SOT recipients and causes significant morbidity and mortality. rESKAPE organisms should be considered when selecting empirical antibiotic therapy for hospitalized SOT recipients presenting with septic shock, particularly those with prior transplantation and antibiotic use.

Epidemiology, antibiotic therapy and outcomes of bacteremia caused by drug-resistant ESKAPE pathogens in cancer patients

Infection due to the six ESKAPE pathogens has recently been identified as a serious emerging problem. However, there is still a lack of information on bacteremia caused by these organisms in cancer patients. We aimed to assess the epidemiology, antibiotic therapy and outcomes of bacteremia due to drug-resistant ESKAPE pathogens (rESKAPE) in patients with cancer. All episodes of bacteremia prospectively documented in hospitalized adults with cancer from 2006 to 2011 were analyzed. Of 1,148 episodes of bacteremia, 392 (34 %) were caused by ESKAPE pathogens. Fifty-four episodes (4.7 %) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium 0, methicillin-resistant Staphylococcus aureus (MRSA) 13, extended-spectrum beta-lactamase (ESLB)-producing Klebsiella pneumoniae 7, carbapenem-resistant Acinetobacter baumannii 4, carbapenem- and quinolone-resistant Pseudomonas aeruginosa 18 and derepression chromosomic ß-lactam and ESBL-producing Enterobacter species 12. Risk factors independently associated with rESKAPE bacteremia were comorbidities, prior antibiotic therapy, urinary catheter and urinary tract source. Inappropriate empirical antibiotic therapy was more frequent in patients with rESKAPE bacteremia than in the other cases (55.6 % vs. 21.5 %, p < 0.001). Persistence of bacteremia (25 % vs. 9.7 %), septic metastasis (8 % vs. 4 %) and early case-fatality rate (23 % vs. 11 %) were more frequent in patients with rESKAPE bacteremia than in patients with other etiologies (p < 0.05). Bacteremia due to rESKAPE pathogens in cancer patients occurs mainly among those with comorbidities who have received prior antibiotic therapy and have a urinary tract source. These patients often receive inappropriate empirical antibiotic therapy and have a poor outcome.

Clinical impact of Gram-negative nonfermenters on adults with community-onset bacteremia in the emergency department

To determine clinical predictors and impact of Gram-negative nonfermenters (GNNFs) infections among adults with community-onset bacteremia in the emergency department (ED). Adults with bacteremia visiting the ED from January 2007 to June 2008 were identified retrospectively. Demographic characteristics, underlying illnesses, clinical conditions, bacteremic pathogens, antimicrobial agents, and outcome, were retrieved from chart records. After the exclusion of 261 patients with contamination of blood cultures and 24 patients referred from other hospitals, 518 adults with community-onset bacteremia were eligible; their mean age was 65.1 years, with slight predominance of female (262 patients, 50.6%). Of a total of 565 bacteremic isolates, Escherichia coli (228 isolates, 40.4%) and Klebsiella pneumoniae (100, 17.7%) were the major microorganisms. GNNFs caused bacteremia in 31 (6.0%) patients. A higher proportion of inappropriate antibiotic therapy in the ED (87.1% vs. 26.5%, p < 0.001) and higher 28-day crude mortality rate (19.4% vs. 8.4%, p = 0.05) were observed in bacteremic patients caused by GNNFs than those not caused by GNNFs. In further analysis of Kaplan-Meier survival curve, patients with GNNF bacteremia had a worse outcome than those due to other pathogens (p = 0.04). Multivariate analysis revealed that the independent predictors related to GNNF bacteremia included surgery during previous 4 weeks prior to ED arrival [odds ratio (OR), 10.79; 95% confidence interval (CI), 1.84-63.24; p = 0.01], residents in long-term healthcare facilities (OR, 4.62; 95% CI, 2.08-10.29; p < 0.001), and malignancy (OR, 2.24; 95% CI, 1.10-5.40; p = 0.02). For adults with bacteremia visiting the ED, GNNF is associated with a higher mortality rate and more inappropriate empirical antibiotic therapy in the ED. To allow early administration of empirical antibiotics, several clinical predictors of GNNF infections were identified.

A New Strategy for Healthcare-Associated Pneumonia: A 2-Year Prospective Multicenter Cohort Study Using Risk Factors for Multidrug-Resistant Pathogens to Select Initial Empiric Therapy

Optimal empiric therapy for hospitalized patients with healthcare-associated pneumonia (HCAP) is uncertain. We prospectively applied a therapeutic algorithm, based on the presence of risk factors for multidrug-resistant (MDR) pathogens in a multicenter cohort study of 445 pneumonia patients, including both community-acquired pneumonia (CAP; n = 124) and HCAP (n = 321). MDR pathogens were more common (15.3% vs 0.8%, P < .001) in HCAP patients than in CAP patients, including Staphylococcus aureus (11.5% vs 0.8%, P < .001); methicillin-resistant S. aureus (6.9% vs 0%, P = .003); Enterobacteriaceae (7.8% vs 2.4%, P = .037); and Pseudomonas aeruginosa (6.9% vs 0.8%, P = .01). Using the proposed algorithm, HCAP patients with ≥2 MDR risk factors, one of which was severity of illness (n = 170), vs HCAP patients with 0-1 risk factor (n = 151) had a significantly higher frequency of MDR pathogens (27.1% vs 2%, P < .001). In total, 93.1% of HCAP patients were treated according to the therapy algorithm, with only 53% receiving broad-spectrum empiric therapy, yet 92.9% received appropriate therapy for the identified pathogen. Thirty-day mortality was significantly higher for HCAP than for CAP (13.7% vs 5.6%, P = .017), but among HCAP patients with 0-1 MDR risk factor, mortality was lower than with ≥2 MDR risk factors (8.6% vs 18.2%, P = .012). In multivariate analysis, initial treatment failure, but not inappropriate empiric antibiotic therapy, was a mortality risk factor (odds ratio, 72.0). Basing empiric HCAP therapy on its severity and the presence of risk factors for MDR pathogens is a potentially useful approach that achieves good outcomes without excessive use of broad-spectrum antibiotic therapy. Japan Medical Association Center for Clinical Trials, JMA-IIA00054.

Neumonía nosocomial

The hospital acquired pneumonia (HAP) is one of the most common infections acquired among hospitalised patients. Within the HAP, the ventilator-associated pneumonia (VAP) is the most common nosocomial infection complication among patients with acute respiratory failure. The VAP and HAP are associated with increased mortality and increased hospital costs. The rise in HAP due to antibiotic-resistant bacteria also causes an increase in the incidence of inappropriate empirical antibiotic therapy, with an associated increased risk of hospital mortality. It is very important to know the most common organisms responsible for these infections in each hospital and each Intensive Care Unit, as well as their antimicrobial susceptibility patterns, in order to reduce the incidence of inappropriate antibiotic therapy and improve the prognosis of patients. Additionally, clinical strategies aimed at the prevention of HAP and VAP should be employed in hospital settings caring for patients at risk for these infections.

Community-acquired Legionella pneumophila pneumonia: a single-center experience with 214 hospitalized sporadic cases over 15 years.

Legionella pneumophila has been increasingly recognized as a cause of community-acquired pneumonia (CAP) and an important public health problem worldwide. We conducted the present study to assess trends in epidemiology, diagnosis, clinical features, treatment, and outcomes of sporadic community-acquired L. pneumophila pneumonia requiring hospitalization at a university hospital over a 15-year period (1995–2010). Among 3934 nonimmunosuppressed hospitalized patients with CAP, 214 (5.4%) had L. pneumophila pneumonia (16 cases were categorized as travel-associated pneumonia, and 21 were part of small clusters). Since the introduction of the urinary antigen test, the diagnosis of L. pneumophila using this method remained stable over the years (p = 0.42); however, diagnosis by means of seroconversion and culture decreased (p < 0.001 and p = 0.001, respectively).The median age of patients with L. pneumophila pneumonia was 58.2 years (SD 13.8), and 76.4% were male. At least 1 comorbid condition was present in 119 (55.6%) patients with L. pneumophila pneumonia, mainly chronic heart disease, diabetes mellitus, and chronic pulmonary disease. The frequency of older patients (aged >65 yr) and comorbidities among patients with L. pneumophila pneumonia increased over the years (p = 0.06 and p = 0.02, respectively). In addition, 100 (46.9%) patients were classified into high-risk classes according to the Pneumonia Severity Index (groups IV–V). Twenty-four (11.2%) patients with L. pneumophila pneumonia received inappropriate empirical antibiotic therapy at hospital admission. Compared with patients who received appropriate empirical antibiotic, patients who received inappropriate therapy more frequently had acute onset of illness (p = 0.004), pleuritic chest pain (p = 0.03), and pleural effusion (p = 0.05). The number of patients who received macrolides decreased over the study period (p < 0.001), whereas the number of patients who received levofloxacin increased (p < 0.001). No significant difference was found in the outcomes between patients who received erythromycin and clarithromycin. However, compared with macrolide use during hospital admission, levofloxacin therapy was associated with a trend toward a shorter time to reach clinical stability (median, 3 vs. 5 d; p = 0.09) and a shorter length of hospital stay (median, 7 vs. 10 d; p < 0.001).Regarding outcomes, 38 (17.8%) patients required intensive care unit (ICU) admission, and the inhospital case-fatality rate was 6.1% (13 of 214 patients). The frequency of ICU admission (p = 0.34) and the need for mechanical ventilation (p = 0.57) remained stable over the study period, but the inhospital case-fatality rate decreased (p = 0.04). In the logistic regression analysis, independent factors associated with severe disease (ICU admission and death) were current/former smoker (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.01–8.62), macrolide use (OR, 2.40; 95% CI, 1.03–5.56), initial inappropriate therapy (OR, 2.97; 95% CI, 1.01–8.74), and high-risk Pneumonia Severity Index classes (OR, 9.1; 95% CI, 3.52–23.4).In conclusion, L. pneumophila is a relatively frequent causative pathogen among hospitalized patients with CAP and is associated with high morbidity. The annual number of L. pneumophila cases remained stable over the study period. In recent years, there have been significant changes in diagnosis and treatment, and the inhospital case-fatality rate of L. pneumophila pneumonia has decreased.

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Introduction: Recent data suggests that patients labeled as having an antimicrobial allergy are at increased risk for in-hospital mortality [Reference 1]. Hypothesis: A reported beta-lactam (BL) allergy increases the risk of inappropriate empiric antibiotic therapy (IEAT) and mortality in patients with gram-negative bacteremia (GNB). Methods: A retrospective analysis of adult patients with GNB was conducted. Data analyzed included BL allergy status, demographics, IEAT, and in-hospital mortality. Co-morbidities were assessed using the McCabe Jackson score and the Charlson co-morbidity index. Severity of illness was evaluated using the APACHE II score. Patients were classified as BL-allergic or non-BL-allergic based on documentation in the medical record. Univariate and multivariate analyses were used to study BL allergy for its association with IEAT (primary endpoint) and with in-hospital mortality (secondary endpoint). Subgroup analyses in patients with healthcare-associated infections (HCAI) and multi-drug resistant organisms (MDRO) were also conducted. Results: A total of 294 patients were included. A BL allergy was noted in 54 patients (18.4%); the type of reaction was specified in only 14 (25.9%) of these patients. The mean APACHE II score was 17.6, and overall in-hospital mortality was 18.7%. HCAI infections and MDRO pathogens were present in 77.9% and 38.4% of patients, respectively. The genitourinary tract was the most common infection source (38.4%), and Escherichia coli was the most commonly cultured pathogen (43.6%). Although IEAT was more common in the allergic group than in the non-allergic group, this difference was not statistically significant (24.1% versus 20.4%, respectively, P > 0.05). In-hospital mortality was also similar between groups (18.5% versus 18.8%, respectively, P > 0.05). No significant differences were noted in either subgroup analysis. Conclusions: Outcomes were similar among patients with and without a BL allergy label in this cohort of patients with GNB. Additional studies are needed to explore the relationship between antimicrobial allergy and clinical outcomes in specific subpopulations. [Reference 1: Pharmacotherapy 2011;31:742-7.]

Different impact of the appropriateness of empirical antibiotics for bacteremia among younger adults and the elderly in the ED

ObjectivesTo investigate the clinical impact of age on bacteremia among adults visiting the emergency department (ED). MethodsBacteremic adults visiting the ED from January 2008 to December 2008 were identified retrospectively. Demographic characteristics, severity, bacteremic pathogens with in vitro susceptibility, antimicrobial agents, and outcomes determined from chart records were analyzed as a case-control study. ResultsOf 518 eligible bacteremic adults, 288 (55.6%) elderly patients (≥65 years old) were case patients and 230 younger patients (<65 years) were regarded as control patients. The 28-day mortality rate was higher in the case patients than that in the control patients (11.8% vs 6.1%, P = .02). The proportion of inappropriate empirical antibiotic therapy between the survivors and nonsurvivors was similar in control patients (69.4% vs 64.3%, P = .77); but for the case patients, the proportion of inappropriate empirical antibiotic therapy in the survivors was lower than that in the non-survivors (27.6% vs 44.1%, P = .04). Of note, inappropriate empirical antibiotic therapy was also one of independent risk factors of 28-day mortality by the multivariate analyses in the case patients (odds ratio [OR] 3.65; P = .049). Other independent predictors of 28-day mortality in case patients included a high Pittsburgh bacteremia score (≥4 points; OR 22.16; P < .001), bacteremia due to foci other than urinary tract infection (OR 9.07; P = .002), malignancy (OR 10.87; P < .001), coronary artery disease (OR 5.68; P = .01), and high serum creatinine (>1.5 mg/dL; OR 3.44; P = .04). ConclusionsFor bacteremic adults, this study demonstrated the impact of inappropriate empirical antibiotic therapy on patients’ outcome in the elderly was greater than that in the younger adults.

Influence of Multidrug Resistance and Appropriate Empirical Therapy on the 30-Day Mortality Rate of Pseudomonas aeruginosa Bacteremia

Infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa are increasing. The aim of our study was to evaluate the influences of appropriate empirical antibiotic therapy and multidrug resistance on mortality in patients with bacteremia due to P. aeruginosa (PAB). Episodes of PAB were prospectively registered from 2000 to 2008. MDR was considered when the strain was resistant to ≥3 antipseudomonal antibiotics. Univariate and multivariate analyses were performed. A total of 709 episodes of PAB were studied. MDR PAB (n = 127 [17.9%]) was more frequently nosocomial and associated with longer hospitalization, bladder catheter use, steroid and antibiotic therapy, receipt of inappropriate empirical antibiotic therapy, and a higher mortality. Factors independently associated with mortality were age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.002 to 1.033), shock (OR, 6.6; 95% CI, 4 to 10.8), cirrhosis (OR, 3.3; 95% CI, 1.4 to 7.6), intermediate-risk sources (OR, 2.5; 95% CI, 1.4 to 4.3) or high-risk sources (OR, 7.3; 95% CI, 4.1 to 12.9), and inappropriate empirical therapy (OR, 2.1; 95% CI, 1.3 to 3.5). To analyze the interaction between empirical therapy and MDR, a variable combining both was introduced in the multivariate analysis. Inappropriate therapy was significantly associated with higher mortality regardless of the susceptibility pattern, and there was a trend toward higher mortality in patients receiving appropriate therapy for MDR than in those appropriately treated for non-MDR strains (OR, 2.2; 95% CI, 0.9 to 5.4). In 47.9% of MDR PAB episodes, appropriate therapy consisted of monotherapy with amikacin. In conclusion, MDR PAB is associated with a higher mortality than non-MDR PAB. This may be related to a higher rate of inappropriate empirical therapy and probably also to amikacin as frequently the only appropriate empirical therapy given to patients with MDR PAB.

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

Infections with resistant Enterobacter spp. are increasingly described, yet data on outcomes associated with these infections are limited. 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. 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. 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 inappropriate empirical antibiotic therapy on outcome of bacteremic adults visiting the ED

ObjectivesTo investigate the clinical impact of inappropriate empirical antibiotics on patient outcome and determine the risk factors for mortality in bacteremic adults who visited the emergency department (ED). MethodsBacteremic adults visiting the ED from January 2007 to June 2008 were identified retrospectively. Demographic characteristics, clinical conditions, bacteremic pathogens, antimicrobial agents, and outcomes were determined from chart records. ResultsThe total of 454 eligible bacteremic adults were included in the analysis; excluded from the study were another 261 patients with contaminated blood cultures and 64 patients with ED stays of less than 24 hours. Among the included individuals, the mean age was 64.6 years, with a small predominance of males (230 patients, 50.7%). Of a total 494 bacteremic isolates, Escherichia coli (206, 41.7%) and Klebsiella species (81, 16.4%) were the most frequently encountered microorganisms. A lower 28-day mortality rate was demonstrated in bacteremic patients treated with appropriate antibiotics than that in those with inappropriate antibiotics or that in those with no antibiotic therapy, as judged by Kaplan-Meier survival curves (P = .01). Moreover, the differences among these three groups achieved higher significance (P = .002) in critically ill patients (Pittsburgh bacteremia scores of ≥4 points). In multivariate analyses, inappropriate antibiotic therapy in the ED was associated independently with mortality at 28 days (odds ratio, 2.26; 95% confidence interval, 1.01-5.13; P = .04). ConclusionsFor bacteremic adults visiting the ED, their outcomes were favorable following appropriate antibiotics, compared to treatment with inappropriate antibiotics or no antibiotics.

Low incidence of multidrug-resistant organisms in patients with healthcare-associated pneumonia requiring hospitalization

Healthcare-associated pneumonia (HCAP) includes a broad spectrum of patients who acquire pneumonia through outpatient contact with the health system. Although limited prospective data exist, it has been suggested that all patients with HCAP should receive empirical therapy with a multidrug regimen directed against drug-resistant organisms. We aimed to determine the differences in aetiology and outcomes between HCAP groups and a community-acquired pneumonia (CAP) group, and to assess the presence of antibiotic-resistant bacteria. All consecutive non-immunocompromised adults hospitalized with pneumonia were prospectively included from 2001 to 2009. Patients who had had recent contact with the health system through nursing homes, home healthcare programmes, haemodialysis clinics or prior hospitalization were considered to have HCAP. A total of 2245 patients with pneumonia were hospitalized through the emergency room, of whom 577 (25.7%) had HCAP. Significant differences in causative pathogens were found between groups. Antibiotic-resistant organisms, including methicillin-resistant Staphylococcus aureus, resistant strains of Pseudomonas aeruginosa, and extendedspectrum β-lactamase-producing Enterobacteriaceae, were scarce in all groups. In contrast, aspiration pneumonia was particularly frequent. No differences were found regarding inappropriate initial empirical antibiotic therapy between groups. Overall mortality was higher in patients who attended a hospital or haemodialysis clinic or received intravenous chemotherapy in the 30 days before pneumonia, and among patients who resided in a nursing home or long-term-care facility. In conclusion, most HCAP patients could be treated in the same way as patients with CAP, after carefully ruling out the presence of aspiration pneumonia.

Community-acquired enterococcal urinary tract infections in hospitalized children

The objectives of this study were to characterize community-acquired (CA) enterococcal urinary tract infections (UTIs) in a tertiary pediatric center and to determine risk factors for their occurrence, their association with renal abnormalities, their antibiotic susceptibility profile, and the appropriateness of the empiric antibiotic treatment, in comparison to those of Gram-negative UTIs. In a 5-year prospective clinical and laboratory study, we found that enterococcal UTIs caused 6.2% (22/355) of culture-proven CA UTIs. Compared with Gram-negative UTI, enterococcal UTI was associated with male predominance, higher rates of underlying urinary abnormalities (70 vs. 43.7%; p = 0.03) and inappropriate empiric antibiotic therapy (22 vs. 5.6%; p = 0.02), and mainly vesicoureteral reflux (53% of cases). This study highlights the importance of early detection of CA enterococcal UTIs because of their association with underlying urinary abnormalities and a high rate of inappropriate empiric antibiotic therapy. Renal imaging is recommended for children with enterococcal UTIs; Gram stain is suggested in selected cases to detect Gram-positive cocci for early diagnosis of enterococcal UTIs and initiation of appropriate antibiotics.

Importance of appropriate empirical antibiotic therapy for methicillin-resistant Staphylococcus aureus bacteraemia

To document the effects of appropriate and inappropriate empirical antibiotic therapy on mortality in a cohort of patients with bacteraemia due to methicillin-resistant Staphylococcus aureus (MRSA) and to summarize effects with previous studies. In the retrospective cohort study, episodes of clinically significant MRSA bacteraemia during a 15 year period were included. Polymicrobial episodes were excluded unless MRSA was isolated in more than one bottle and co-pathogens were given appropriate empirical antibiotic treatment. Appropriate empirical treatment was defined as matching in vitro susceptibility and started within 48 h of blood-culture taking, except for single aminoglycosides or rifampicin. We assessed univariate and multivariate associations between appropriate empirical therapy and 30 day all-cause mortality. Multivariable analysis was conducted using backward stepwise logistic regression. We reviewed all studies assessing the effects of appropriate empirical antibiotic treatment on mortality for MRSA infections and compiled adjusted odds ratios (ORs) using a random effects meta-analysis. Five hundred and ten episodes of MRSA bacteraemia were included. There were no cases of community-acquired infection. The 30 day mortality was 43.9% (224/510) and was stable throughout the study period. Mortality was significantly higher among patients receiving inappropriate (168/342, 49.1%) compared with those receiving appropriate (56/168, 33.3%) empirical antibiotic treatment, P = 0.001. In the adjusted analysis the OR was 2.15 [95% confidence interval (CI) 1.34-3.46]. Pooling of six studies using adequate methodology for the adjusted analysis resulted in an OR of 1.98 (95% CI 1.62-2.44). Appropriate empirical antibiotic treatment has a significant survival benefit in MRSA bacteraemia. Treatment guidelines should consider this benefit.

Pseudomonas aeruginosa bacteremia: resistance to antibiotics, risk factors, and patient mortality

The aim of our study was to determine the prevalence of Pseudomonas aeruginosa bacteremia, risk factors, and outcome of patients treated at the Hospital of Kaunas University of Medicine. All hospitalized patients with blood culture positive for Pseudomonas aeruginosa during the 5-year period were included. A retrospective data analysis was performed to evaluate patients' risk factors and mortality caused by P. aeruginosa bacteremia. A total of 47 (58.8%) bacteremia episodes occurred in an intensive care unit (ICU). A primary source of bacteremia was identified in 50 (62.5%) episodes. Overall mortality rate was 58.8%. Univariate risk factors analysis showed the factors, which significantly increased the risk of death: mechanical ventilation (13.67 times, P<0.001), patient hospitalization in the ICU (8.51 times, P<0.001), acute respiratory failure (8.44 times, P<0.001), infection site in the respiratory tract (4.93 times, P=0.003), and central vein catheter (4.44 times, P=0.002). Timely and appropriate treatment and surgery were significant protective factors for 30-day mortality (11.1 and 5.26 times, respectively; P=0.001). Meropenem-resistant Pseudomonas aeruginosa strains caused bacteremia more frequently in patients older than 65 years than meropenem-sensitive strains (57.9%, n=11). All 19 patients with meropenem-resistant Pseudomonas aeruginosa bacteremia received inappropriate empirical antibiotic therapy. Treatment at the intensive care unit, mechanical ventilation, acute respiratory failure, source of infection in respiratory tract, and central vein catheter are the major risk factors associated with an increased mortality rate in patients with Pseudomonas aeruginosa bacteremia. The patients older than 65 years are at increased risk for bacteremia caused by carbapenem-resistant Pseudomonas aeruginosa strains. Carbapenems are not antibiotics of the choice of treatment for Pseudomonas aeruginosa bacteremia at the Hospital of Kaunas University of Medicine.

Bloodstream Infections and Clinical Significance of Healthcare-associated Bacteremia: A Multicenter Surveillance Study in Korean Hospitals

Recent changes in healthcare systems have changed the epidemiologic paradigms in many infectious fields including bloodstream infection (BSI). We compared clinical characteristics of community-acquired (CA), hospital-acquired (HA), and healthcare-associated (HCA) BSI. We performed a prospective nationwide multicenter surveillance study from 9 university hospitals in Korea. Total 1,605 blood isolates were collected from 2006 to 2007, and 1,144 isolates were considered true pathogens. HA-BSI accounted for 48.8%, CA-BSI for 33.2%, and HCA-BSI for 18.0%. HA-BSI and HCA-BSI were more likely to have severe comorbidities. Escherichia coli was the most common isolate in CA-BSI (47.1%) and HCA-BSI (27.2%). In contrast, Staphylococcus aureus (15.2%), coagulase-negative Staphylococcus (15.1%) were the common isolates in HA-BSI. The rate of appropriate empiric antimicrobial therapy was the highest in CA-BSI (89.0%) followed by HCA-BSI (76.4%), and HA-BSI (75.0%). The 30-day mortality rate was the highest in HA-BSI (23.0%) followed by HCA-BSI (18.4%), and CA-BSI (10.2%). High Pitt score and inappropriate empirical antibiotic therapy were the independent risk factors for mortality by multivariate analysis. In conclusion, the present data suggest that clinical features, outcome, and microbiologic features of causative pathogens vary by origin of BSI. Especially, HCA-BSI shows unique clinical characteristics, which should be considered a distinct category for more appropriate antibiotic treatment.

Extended-spectrum beta-lactamase-producing Escherichia coli in patients with travellers’ diarrhoea

The identification of patients carrying extended-spectrum beta-lactamase (ESBL)-producing bacteria is important, since these patients are at risk of receiving inappropriate empirical therapy if they become infected. The purpose of this study was to investigate the occurrence of ESBL-producing bacteria in patients with travellers' diarrhoea. Patients with travellers' diarrhoea (N = 242) having delivered stool samples for the diagnosis of Salmonella, Shigella, Yersinia or Campylobacter, were also examined for ESBL-producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. The overall prevalence of faecal carriage of ESBL-producing bacteria was 24% (58/242). Of the patients who had travelled in Europe, 3% (2/63) were found to be ESBL carriers in comparison to 36% (50/138) of those who had travelled outside Europe. ESBL-producing E. coli was especially common among patients returning from India (11/14), Egypt (19/38; 50%) and Thailand (8/38; 22%). In total, 90% of the genes of the ESBL-positive samples were of CTX-M type. The CTX-M-1 group dominated, followed by the CTX-M-9 group. The repetitive sequence-based PCR fingerprint pattern showed that there was no similarity between the ESBL strains found. Patients who have travelled outside Europe are at high risk of being colonized with ESBL-producing Enterobacteriaceae, and, if infected, are also at risk of receiving inappropriate empirical antibiotic therapy.

Pneumonia associada à ventilação mecânica: epidemiologia e impacto na evolução clínica de pacientes em uma unidade de terapia intensiva

Although ventilator-associated pneumonia (VAP) is a major cause of nosocomial infection, its role in the prognosis of patients remains undefined. The objective of this study was to evaluate the impact of VAP on the clinical evolution of patients. This was a prospective cohort study involving 233 patients on mechanical ventilation (VAP group, n = 64; control group, n = 169). Primary outcomes were time on mechanical ventilation (TMV), time in ICU (TICU), overall length of hospital stay (LHS) and in-ICU mortality. Secondary outcomes were in-hospital mortality, microbiological profile, prior use of antibiotics and risk factors for VAP acquisition. Control and VAP group outcomes were, respectively, as follows: median TMV (days), 9 (interquartile range [IQR]: 5-15) and 23 (IQR: 15-37; p < 0.0001); median TICU (days), 12 (IQR: 8-21) and 27 (IQR: 17-42; p < 0.0001); median LHS (days), 33 (IQR: 18-64) and 46 (IQR: 25-90; p = 0.05); and in-ICU mortality, 38% (95% CI: 31-45) and 55% (95% CI: 42-67; p = 0.02). VAP was a predictor of in-ICU mortality (OR = 3.40; 95% CI: 1.54-7.48). TMV (OR = 2.27; 95% CI: 1.05-4.87) and prior use of antibiotics (OR = 1.07; 95% CI: 1.04-1.10) were risk factors for VAP. VAP did not affect in-hospital mortality. Acinetobacter spp. was the most common isolate (28%). Inappropriate empirical antibiotic therapy was administered in 48% of cases. In this study, there was a high incidence of infection with resistant bacteria and inappropriate initial antibiotic therapy. Long TMV and prior use of antibiotics are risk factors for VAP.

Treatment options for nosocomial pneumonia due to MRSA

Nosocomial pneumonia, which includes hospital-acquired pneumonia, ventilator-associated pneumonia, and health care associated pneumonia, remains an important cause of morbidity and mortality. The continuing emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a nosocomial pneumonia pathogen is particularly problematic not only because of its prevalence, but also because antimicrobial resistance is increasingly associated with inappropriate empirical antibiotic therapy. As a result, intensivists are faced with the dual goals of providing initial accurate broad-spectrum antibiotic coverage to reduce mortality while minimizing the risk for the emergence of antimicrobial resistance. These competing goals can be achieved by using an approach that initially delivers liberal broad-spectrum coverage followed by de-escalation once culture results and serial clinical observations become available. In ventilator-associated pneumonia, linezolid has demonstrated favorable activity against Gram-positive bacteria, including MRSA, and is recommended in evidence-based guidelines as an alternative to vancomycin, particularly when MRSA is documented as the etiology.

Health Care–Associated Pneumonia Requiring Hospital Admission

Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. However, limited data exist to validate this entity. We aimed to ascertain the epidemiology, causative organisms, antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for HCAP requiring hospitalization. Observational analysis of a prospective cohort of nonseverely immunosuppressed hospitalized adults with pneumonia. Patients who had recent contact with the health care system through nursing homes, home health care programs, hemodialysis clinics, or prior hospitalization were considered to have HCAP. Of 727 cases of pneumonia, 126 (17.3%) were HCAP and 601 (82.7%) were community acquired. Compared with patients with community-acquired pneumonia, patients with HCAP were older (mean age, 69.5 vs 63.7 years; P < .001), had greater comorbidity (95.2% vs 74.7%; P < .001), and were more commonly classified into high-risk pneumonia severity index classes (67.5% vs 48.8%; P < .001). The most common causative organism was Streptococcus pneumoniae in both groups (27.8% vs 33.9%). Drug-resistant pneumococci were more frequently encountered in cases of HCAP. Legionella pneumophila was less common in patients with HCAP (2.4% vs 8.8%; P = .01). Aspiration pneumonia (20.6% vs 3.0%; P < .001), Haemophilus influenzae (11.9% vs 6.0%; P = .02), Staphylococcus aureus (2.4% vs 0%; P = .005), and gram-negative bacilli (4.0% vs 1.0%; P = .03) were more frequent in HCAP. Patients with HCAP more frequently received an initial inappropriate empirical antibiotic therapy (5.6% vs 2.0%; P = .03). The overall case-fatality rate (< 30 days) was higher in patients with HCAP (10.3% vs 4.3%; P = .007). At present, a substantial number of patients initially seen with pneumonia in the emergency department have HCAP. These patients require a targeted approach when selecting empirical antibiotic therapy.