Inadequate Initial Antimicrobial Therapy Research Articles

Clinical and economical improvements after introducing rapid identification of bacteria and early antibiotic susceptibility testing in sepsis and bloodstream infections. Results of the PHENOMENON study.

Background: Sepsis and bloodstream infections pose severe challenges in intensive care. Early reliable diagnosis is the key to successful therapy. The objective of the study presented here was to investigate the clinical and economical effects of the new PhenoTM BC test, which allows bacteria identification (ID) and antimicrobial susceptibility testing (AST) in approximately 7 hours after a blood culture becomes positive (BC+).Methods: Historically controlled interventional study. Population: patients with BC+ and ICU admission. Inadequate initial antimicrobial therapy (IAT) is need of therapy change based on result. Prospectively the new test was used in addition. Primary endpoint: time-to-result in hours. Contribution margin (CM) i.e. revenue – costs was computed. All patients formed the intention-to-treat population (ITT). Patients with complete cost data formed the modified ITT group (mITT). CM results were calculated for mITT and PP. Further analyses: length-of-stay (LOS) and mortality.Results: 223 historical and 200 prospective patients were included. Time to result (ITT) was shortened by 51.1 hours (83 vs. 31.9; p<0.001). Overall savings (mITT) were 257,100 € (–301,264 € vs. –44,164 €). 143 of 181 (79%) patients had a test performed, 126 of 143 (88%) having a clinically useable result. 40 (32%) had IAT vs. 65 (29%) in the historic cohort. Median time to AST in PP was shortened by 61.7 hours (89.5 vs. 27.8; p<0.001). LOS was shortened 7 days (28 vs. 19; p=0.226) and mortality was 8% (40.5% vs. 32.5%; p=0.440) lower. Median CM +3,074.80 € per case (–2,350.50 € vs. +724.70 €; p=0.040). Conclusion: The new PhenoTM ID+AST test leads to faster and clinically meaningful results and saves money by shortening LOS on the ICU.

Impact of species and antibiotic therapy of enterococcal peritonitis on 30-day mortality in critical care\u2014an analysis of the OUTCOMEREA database

IntroductionEnterococcus species are associated with an increased morbidity in intraabdominal infections (IAI). However, their impact on mortality remains uncertain. Moreover, the influence on outcome of the appropriate or inappropriate status of initial antimicrobial therapy (IAT) is subjected to debate, except in septic shock. The aim of our study was to evaluate whether an IAT that did not cover Enterococcus spp. was associated with 30-day mortality in ICU patients presenting with IAI growing with Enterococcus spp.Material and methodsRetrospective analysis of French database OutcomeRea from 1997 to 2016. We included all patients with IAI with a peritoneal sample growing with Enterococcus. Primary endpoint was 30-day mortality.ResultsOf the 1017 patients with IAI, 76 (8%) patients were included. Thirty-day mortality in patients with inadequate IAT against Enterococcus was higher (7/18 (39%) vs 10/58 (17%), p = 0.05); however, the incidence of postoperative complications was similar. Presence of Enterococcus spp. other than E. faecalis alone was associated with a significantly higher mortality, even greater when IAT was inadequate. Main risk factors for having an Enterococcus other than E. faecalis alone were as follows: SAPS score on day 0, ICU-acquired IAI, and antimicrobial therapy within 3 months prior to IAI especially with third-generation cephalosporins. Univariate analysis found a higher hazard ratio of death with an Enterococcus other than E. faecalis alone that had an inadequate IAT (HR = 4.4 [1.3–15.3], p = 0.019) versus an adequate IAT (HR = 3.1 [1.0–10.0], p = 0.053). However, after adjusting for confounders (i.e., SAPS II and septic shock at IAI diagnosis, ICU-acquired peritonitis, and adequacy of IAT for other germs), the impact of the adequacy of IAT was no longer significant in multivariate analysis. Septic shock at diagnosis and ICU-acquired IAI were prognostic factors.ConclusionAn IAT which does not cover Enterococcus is associated with an increased 30-day mortality in ICU patients presenting with an IAI growing with Enterococcus, especially when it is not an E. faecalis alone. It seems reasonable to use an IAT active against Enterococcus in severe postoperative ICU-acquired IAI, especially when a third-generation cephalosporin has been used within 3 months.

Impact of inadequate initial antimicrobial therapy on mortality in patients with bacteraemic cholangitis: a retrospective cohort study

ObjectivesAcute cholangitis is a common cause of bacteraemia resulting in severe sepsis or septic shock. The impact of the appropriate initial antimicrobial therapy on short-term mortality in bacteraemic cholangitis has not been well investigated. MethodsWe conducted a retrospective cohort study of patients with bacteraemic cholangitis at two large tertiary care centres in Tokyo, Japan between 2009 and 2015. We determined the factors associated with 30-day all-cause mortality from the date of drawing the first positive blood culture, using a multivariate logistic regression analysis. ResultsWe identified 573 patients with bacteraemic cholangitis (median age, 77 years; male, 58.3%). The 30-day all-cause mortality rate was 6.6% (38/573). Inadequate initial antimicrobial therapy occurred in 133 (23.2%) patients. Factors associated with 30-day all-cause mortality included the Charlson co-morbidity index score >3 (adjusted odds ratio (aOR) 4.12; 95% CI 1.18–14.38), jaundice (total bilirubin >2.5 mg/dL) (aOR 3.39; 95% CI 1.46–7.89), septic shock within 48 h of the first positive blood culture (aOR 3.34; 95% CI 1.42–7.89), biliary obstruction due to hepatobiliary malignancy (aOR 8.00; 95% CI 2.92–21.97), and inadequate initial antimicrobial therapy (aOR 2.78; 95% CI 1.27–6.11). ConclusionsInadequate initial antimicrobial therapy was an important, modifiable determinant of survival.

Bloodstream infections caused by Klebsiella pneumoniae in onco-hematological patients: clinical impact of carbapenem resistance in a multicentre prospective survey.

The aim of this study was to identify risk factors for mortality in patients suffering from hematological malignancies (HMs) with bloodstream infections (BSIs) caused by Klebsiella pneumoniae (KP). We conducted a prospective cohort study on KP BSI in 13 Italian hematological units participating in the HEMABIS registry-SEIFEM group. The outcome measured was death within 21 days of BSI onset. Survivor and non-survivor subgroups were compared and Cox regression analysis was conducted to identify independent predictors of mortality. A total of 278 episodes of KP BSI were included in the study between January 2010 and June 2014. We found that 161 (57.9%) KP isolates were carbapenem resistant (CRKP). The overall 21-day mortality rate was 36.3%. It was significantly higher for patients with CRKP BSI (84/161, 52.2%) than for those with BSI caused by carbapenem susceptible KP (CSKP) (17/117, 14.5%; P < 0.001). Septic shock (HR 3.86), acute respiratory failure (HR 2.32), inadequate initial antimicrobial therapy (HR 1.87) and carbapenem resistance by KP isolates (HR 1.85) were independently associated with mortality. A subanalysis was conducted in only 149 patients with CRKP BSI who had received ≥48 hr of adequate antibiotic therapy, and combination therapy was independently associated with survival (HR 0.32). Our study shows that in recent years carbapenem resistance has dramatically increased in HM patients with KP BSI in Italy and is associated with a worse outcome. The optimal management of such infections and the definition of new empirical/targeted antimicrobial strategies in HM patients can still be considered unmet clinical needs. Am. J. Hematol. 91:1076-1081, 2016. © 2016 Wiley Periodicals, Inc.

Prevalence, risk factors, and impact on clinical outcome of extended-spectrum beta-lactamase-producing Escherichia coli bacteraemia: a five-year study

The impact of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) bacteraemia on outcome remains controversial. A retrospective analysis of the prevalence, risk factors, clinical features, and outcomes of all ESBL-EC bacteraemia in one French hospital over a 5-year period was performed. A case-control study was undertaken: cases had at least one ESBL-EC bacteraemia and controls a positive non-ESBL-EC bacteraemia. The prevalence of ESBL-EC bacteraemia increased from 5.2% of all positive E. coli blood cultures in 2005 to 13.5% in 2009 (p<0.003). CTX-M represented 70% of ESBL-EC bacteraemia strains, and strains were not clonally related. On adjusted analysis, the only significant risk factor for ESBL-EC bacteraemia was a previous ESBL-EC colonization (odds ratio 11.3, 95% confidence interval 1.2-107; p=0.003). Initial antimicrobial therapy was less frequently adequate in the ESBL-EC group (48% vs. 85%; p=0.003). The presence of ESBL-EC bacteraemia was not associated with a longer hospital stay (p=0.088). Day 30 mortality was high, but not significantly different in the two groups (30% vs. 27%; p=0. 82). The prevalence of ESBL-EC bacteraemia has been increasing dramatically. Previous colonization with ESBL-EC was a strong risk factor for ESBL-EC bacteraemia. More inadequate initial antimicrobial therapy was noted in the ESBL-EC group, but mortality and length of hospital stay were not significantly different from those of patients with non-ESBL-EC bacteraemia.

Predictors of Mortality in Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae: Importance of Combination Therapy

The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens is a major challenge for clinicians. In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P = .02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio [OR]: 7.17; 95% confidence interval [CI]: 1.65-31.03; P = .008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61-10.76; P = .003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02-1.07; P < .001). Postantibiogram therapy with a combination of tigecycline, colistin, and meropenem was associated with lower mortality (OR: 0.11; 95% CI: .02-.69; P = .01). KPC-Kp BSIs are associated with high mortality. To improve survival, combined treatment with 2 or more drugs with in vitro activity against the isolate, especially those also including a carbapenem, may be more effective than active monotherapy.

Multidrug-Resistant Proteus mirabilis Bloodstream Infections: Risk Factors and Outcomes

Our aims were to identify (i) risk factors associated with the acquisition of multidrug-resistant (MDR, to 3 or more classes of antimicrobials) Proteus mirabilis isolates responsible for bloodstream infections (BSIs) and (ii) the impact on mortality of such infections. Risk factors for acquiring MDR P. mirabilis BSIs were investigated in a case-case-control study; those associated with mortality were assessed by comparing survivors and nonsurvivors in a cohort study. The population consisted of 99 adult inpatients with P. mirabilis BSIs identified by our laboratory over an 11-year period (1999 to 2009), 36 (33.3%) of which were caused by MDR strains, and the overall 21-day mortality rate was 30.3%. Acquisition of an MDR strain was independently associated with admission from a long-term care facility (odds ratio [OR], 9.78; 95% confidence interval [CI], 1.94 to 49.16), previous therapy with fluoroquinolones (OR, 5.52; 95% CI, 1.30 to 23.43) or oxyimino-cephalosporins (OR, 4.72; 95% CI, 1.31 to 16.99), urinary catheterization (OR, 3.89; 95% CI, 1.50 to 10.09), and previous hospitalization (OR, 2.68; 95% CI, 10.4 to 6.89). Patients with MDR P. mirabilis BSIs received inadequate initial antimicrobial therapy (IIAT, i.e., treatment with drugs to which the isolate displayed in vitro resistance) more frequently than those with non-MDR infections; they also had increased mortality and (for survivors) longer post-BSI-onset hospital stays. In multivariate regression analysis, 21-day mortality was associated with septic shock at BSI onset (OR, 12.97; 95% CI, 32.2 to 52.23), P. mirabilis isolates that were MDR (OR, 6.62; 95% CI, 16.4 to 26.68), and IIAT (OR, 9.85; 95% CI, 26.7 to 36.25), the only modifiable risk factor of the 3. These findings can potentially improve clinicians' ability to identify P. mirabilis BSIs likely to be MDR, thereby reducing the risk of IIAT--a major risk factor for mortality in these cases--and facilitating the prompt implementation of appropriate infection control measures.

Mortality risk factors in patients with Acinetobacter baumannii ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii has contributed to high mortality rate, prolonged stays in the intensive care unit, and the rapid development of antimicrobial resistance to commonly used antimicrobials. This study sought to determine predictors of mortality and carbapenem resistance for patients with A baumannii VAP. We retrospectively reviewed 541 adult patients with A baumannii pneumonia, who were admitted to a medical center between 2005 and 2007; of which 180 (33.3%) had been treated with mechanical ventilation. Of the 180 patients, 98 (54.4%) who survived were categorized as the survivor group, and 82 (45.6%) who died as the mortality group. Eighty-seven (48.3%) with imipenem-sensitive A baumannii VAP were categorized as the IS-AB group, and the remaining 93 (51.7%) with imipenem-resistant VAP as the IR-AB group. Compared with the survivor group, the mortality group had significantly higher Charlson comorbidity index scores, and more neoplastic disease, other sites of infection, bloodstream infections, altered mental status, confusion, urea >7mmol/L, respiratory rate >30/min, low blood pressure (systolic <90mmHg or diastolic <60mmHg), age >65 years (CURB-65)≥3, creatinine>1.6mg/dL, C-reactive protein≥100mg/L, and imipenem resistance. The survivor group had more cases of tracheostomy and diabetes mellitus than the mortality group had. Compared with the IS-AB group, the IR-AB group had higher Charlson comorbidity index scores, longer stays before VAP onset, an increase in other sites of infection, white blood cell count <4/μL or >1.1×10(4)/μL, and higher hospital mortality rates. Inadequate initial empiric antimicrobial therapy and higher disease severity scores, including CURB≥3 and C-reactive protein≥120mg/L, were independent risk factors associated with higher mortality rates for A baumannii pneumonia. Length of stay before VAP and white blood cell count <4/μL or >1.1×10(4)/μL were independent risk factors for carbapenem resistance.

Multidrug-resistant Pseudomonas aeruginosa bloodstream infections: risk factors and mortality

We retrospectively studied patients diagnosed with P. aeruginosa bloodstream infections (BSIs) in two Italian university hospitals. Risk factors for the isolation of multidrug-resistant (MDR) or non-MDR P. aeruginosa in blood cultures were identified by a case-case-control study, and a cohort study evaluated the clinical outcomes of such infections. We identified 106 patients with P. aeruginosa BSI over the 2-year study period; 40 cases with MDR P. aeruginosa and 66 cases with non-MDR P. aeruginosa were compared to 212 controls. Independent risk factors for the isolation of MDR P. aeruginosa were: presence of central venous catheter (CVC), previous antibiotic therapy, and corticosteroid therapy. Independent risk factors for non-MDR P. aeruginosa were: previous BSI, neutrophil count <500/mm3, urinary catheterization, and presence of CVC. The 21-day mortality rate of all patients was 33·9%. The variables independently associated with 21-day mortality were presentation with septic shock, infection due to MDR P. aeruginosa, and inadequate initial antimicrobial therapy.

Extended-spectrum β-lactamase producing Escherichia coli: changing epidemiology and clinical impact

This review discusses the recent findings (July 2008-January 2010) on extended-spectrum [beta]-lactamase (ESBL)-producing Escherichia coli, mainly focussed on the epidemiology and clinical impact of infections owing to this pathogen. CTX-M-producing E. coli, mainly the CTX-M-15 producers, has emerged and disseminated worldwide as an important cause of both nosocomial and community-onset infections. The clonal spread of the ST131 epidemic E. coli strain is linked not only to the CTX-M-15 pandemia but also to other ESBLs types. The most commonly reported risk factors for community-onset ESBL-producing E. coli infections are contact with healthcare centres, recent use of antimicrobial agents, and presence of comorbidities. But infections owing to ESBL-producing E. coli in patients without obvious risk factors can occur, probably related to the increase of healthy carriers colonized with this pathogen. The main significant predictor of mortality caused by ESBL-producing E. coli is inadequate initial antimicrobial therapy. Alternatives of treatment of severe ESBL-producing E. coli infections included carbapenems, amikacin, tigecycline, and [beta]-lactam/[beta]-lactamase inhibitor combinations; with some of them enough clinical evidence is lacking (tigecycline, [beta]-lactam/[beta]-lactamase inhibitor combinations). For urinary tract infections, fosfomycin and nitrofurantoin could be useful. The worldwide emergence of multiresistant ESBL-producing E. coli raises key therapeutic problems; interventions addressed to their quick detection and early appropriate antibiotic treatment and prevention are urgently needed.

Incidence and clinical impact of extended-spectrum-β-lactamase (ESBL) production and fluoroquinolone resistance in bloodstream infections caused by Escherichia coli in patients with hematological malignancies

To identify risk factors for mortality in patients suffering from hematological malignancies with concurrent bacteremia caused by Escherichia coli. Particular attention was focused on defining the impact of extended-spectrum-beta-lactamase (ESBL) production and fluoroquinolone resistance by the bacterial isolates on mortality. A retrospective eight-year cohort study design was employed. The outcome measured was death within 30 days of the first positive blood culture. Survivor and non-survivor subgroups were compared to identify predictors of mortality. A total of 62 episodes of bacteremia caused by E. coli were analyzed. The overall incidences of ESBL production and fluoroquinolone resistance were 41.9% and 62.9%, respectively. The overall 30-day mortality rate was 20.9% (13/62). In a multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (OR=14.96, 95% CI 1.95-114.51; P=0.009), infection caused by ESBL-producing isolates (OR=8.84, 95% CI 1.48-52.91; P=0.01), and prolonged neutropenia (OR=8.10, 95% CI 1.29-50.57; P=0.02). Sound knowledge of the local distribution of pathogens and their susceptibility patterns and prompt initiation of effective antimicrobial treatment are essential in patients suffering from hematological malignancies with BSIs caused by E. coli.

Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase- Producing Escherichia coli : Risk Factors for Inadequate Initial Antimicrobial Therapy

Extended-spectrum-beta-lactamase (ESBL)-producing strains of Escherichia coli are a significant cause of bloodstream infections (BSI) in hospitalized and nonhospitalized patients. We previously showed that delaying effective antimicrobial therapy in BSI caused by ESBL producers significantly increases mortality. The aim of this retrospective 7-year analysis was to identify risk factors for inadequate initial antimicrobial therapy (IIAT) (i.e., empirical treatment based on a drug to which the isolate had displayed in vitro resistance) for inpatients with BSI caused by ESBL-producing E. coli. Of the 129 patients considered, 56 (43.4%) received IIAT for 48 to 120 h (mean, 72 h). Independent risk factors for IIAT include an unknown BSI source (odds ratios [OR], 4.86; 95% confidence interval [CI], 1.98 to 11.91; P = 0.001), isolate coresistance to >or=3 antimicrobials (OR, 3.73; 95% CI, 1.58 to 8.83; P = 0.003), hospitalization during the 12 months preceding BSI onset (OR, 3.33; 95% CI, 1.42 to 7.79; P = 0.005), and antimicrobial therapy during the 3 months preceding BSI onset (OR, 2.65; 95% CI, 1.11 to 6.29; P = 0.02). IIAT was the strongest risk factor for 21-day mortality and significantly increased the length of hospitalization after BSI onset. Our results underscore the need for a systematic approach to the management of patients with serious infections by ESBL-producing E. coli. Such an approach should be based on sound, updated knowledge of local infectious-disease epidemiology, detailed analysis of the patient's history with emphasis on recent contact with the health care system, and aggressive attempts to identify the infectious focus that has given rise to the BSI.

Impact of appropriateness of initial antibiotic therapy on outcome of postoperative pneumonia

Although delay in the administration of appropriate antibiotic treatment for ventilator-associated or community-acquired pneumonia is associated with increased hospital mortality, impact of appropriateness of initial antibiotic therapy on outcome of postoperative pneumonia has been poorly investigated. Of 7,275 patients who had undergone intraabdominal surgery under general anesthesia between January 1998 and December 2005, we compiled a list of 101 patients with microbiologically confirmed postoperative pneumonia. We analyzed the influence of the appropriateness of initial antibiotic therapy on outcome of postoperative pneumonia using logistic regression analysis. Among the patients with postoperative pneumonia, about a half received inadequate initial antimicrobial therapy. As well as the presence of concomitant intraabdominal abscess [odds ratio (OR) = 28.83), prolonged duration of anesthesia at surgery (OR = 22.41), and the isolation of methicillin-resistant Staphylococcus aureus (OR = 8.86), inadequate initial antibiotic therapy was a determinant of death from postoperative pneumonia (OR = 16.75). The outcomes of patients with postoperative pneumonia could be improved by avoiding concomitant intraabdominal abscess, reducing surgical insult, and administering appropriate antimicrobial agents.

Predictors of Mortality in Patients with Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae : Importance of Inadequate Initial Antimicrobial Treatment

Bloodstream infections (BSI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms markedly increase the rates of treatment failure and death. We conducted a retrospective cohort analysis to identify risk factors for mortality in adult in-patients with BSI caused by ESBL-producing Enterobacteriaceae (ESBL-BSI). Particular attention was focused on defining the impact on the mortality of inadequate initial antimicrobial therapy (defined as the initiation of treatment with active antimicrobial agents >72 h after collection of the first positive blood culture). A total of 186 patients with ESBL-BSI caused by Escherichia coli (n = 104), Klebsiella pneumoniae (n = 58), or Proteus mirabilis (n = 24) were identified by our microbiology laboratory from 1 January 1999 through 31 December 2004. The overall 21-day mortality rate was 38.2% (71 of 186). In multivariate analysis, significant predictors of mortality were inadequate initial antimicrobial therapy (odds ratio [OR] = 6.28; 95% confidence interval [CI] = 3.18 to 12.42; P < 0.001) and unidentified primary infection site (OR = 2.69; 95% CI = 1.38 to 5.27; P = 0.004). The inadequately treated patients (89 of 186 [47.8%]) had a threefold increase in mortality compared to the adequately treated group (59.5% versus 18.5%; OR = 2.38; 95% CI = 1.76 to 3.22; P < 0.001). The regimens most commonly classified as inadequate were based on oxyimino cephalosporin or fluoroquinolone therapy. Prompt initiation of effective antimicrobial treatment is essential in patients with ESBL-BSI, and empirical decisions must be based on a sound knowledge of the local distribution of pathogens and their susceptibility patterns.

Early evolution of arterial oxygenation in severe community-acquired pneumonia: A prospective observational study

Purpose Acute respiratory failure requiring mechanical ventilation in severe community-acquired pneumonia has been shown to be a significant negative prognostic factor. We analyzed the early evolution of the Pa o 2/F io 2 ratio and evaluated its clinical value as an outcome predictor. Materials and methods This is a prospective study conducted in a tertiary referral hospital. In 62 adult patients requiring early mechanical ventilation due to severe community-acquired pneumonia, we measured serial changes in Pa o 2/F io 2 ratio and other clinical variables within the first 48 hours of mechanical ventilation and compared the difference between survivors and nonsurvivors. Results The initial Pa o 2/F io 2 ratio was lower in nonsurvivors (n = 27) than in survivors (n = 35) (158.0 ± 55.8 vs 117.9 ± 50.6, P = .025). Over the next 48 hours, the ratio increased significantly in survivors but not in nonsurvivors (analysis of variance, P < .001). An increase in Pa o 2/F io 2 ratio greater than 56 mm Hg had a sensitivity of 75% and a specificity of 81% of survival. A definite causative pathogen was identified in 36 patients (58%) and the 3 most commonly isolated pathogens were Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae. Ten patients received inadequate initial empirical antimicrobial therapy, in which the Pa o 2/F io 2 ratio change was significantly less than those who were adequately treated (analysis of variance, P < .001). Mortality was much higher (86% [6/7]) in patients who received inadequate antibiotics and where Pa o 2/F io 2 ratio change was less than 56 mm Hg. On multivariate analysis, trend changes in Pa o 2/F io 2 ratio over 48 hours, shock, and Acute Physiology and Chronic Health Evaluation II score were documented to be independent predictors of mortality. Conclusions A progressive improvement of Pa o 2/F io 2 ratio during the first 48 hours of mechanical ventilation indicates favorable outcome. Serial measurement of this ratio should be considered in decision making for therapeutic strategy.

Community-Acquired Listeria monocytogenes Meningitis in Adults

Listeria monocytogenes is the third most common cause of bacterial meningitis. We prospectively evaluated 30 episodes of community-acquired L. monocytogenes meningitis, confirmed by culture of cerebrospinal fluid specimens, in a nationwide study in The Netherlands. Outcome was graded using the Glasgow outcome score; an unfavorable outcome was defined as a score of 1-4. We found 30 episodes of L. monocytogenes meningitis. All patients were immunocompromised or > 50 years old. In 19 (63%) of 30 patients, symptoms were present for > 24 h; in 8 patients (27%), symptoms were present for > or = 4 days. The classic triad of fever, neck stiffness, and change in mental status was present in 13 (43%) of 30 patients. An individual cerebrospinal fluid indicator of bacterial meningitis was present in 23 (77%) of 30 cases. Gram staining of cerebrospinal fluid samples revealed the causative organism in 7 (28%) of 25 cases. The initial antimicrobial therapy was amoxicillin based for 21 (70%) of 30 patients. The coverage of initial antimicrobial therapy was microbiologically inadequate for 9 (30%) of the patients. The mortality rate was 17% (5 of 30), and 8 (27%) of 30 patients experienced an unfavorable outcome. Inadequate initial antimicrobial therapy was not related to outcome. In contrast with previous reports, we found that patients with meningitis due to L. monocytogenes do not present with atypical clinical features; however, typical cerebrospinal fluid findings predictive for bacterial meningitis might be absent. A high proportion of patients received initial antimicrobial therapy that did not cover L. monocytogenes.

Staphylococcus aureus bacteraemia: incidence, risk factors and predictors for death in a Brazilian teaching hospital

The aim of this study was to evaluate the incidence of bloodstream infection due to Staphylococcus aureus and the risk factors for mortality. The design was a two-year retrospective cohort of patients more than one year of age with clinically significant and microbiologically documented bloodstream infection due to S. aureus between January 2000 and December 2001 in a tertiary teaching hospital in midwest Brazil. One hundred and eleven patients were identified with clinically significant and microbiologically confirmed bacteraemia due to S. aureus, accounting for an infection rate of five per 1000 admissions. Nosocomial infections represented 83.8% of cases and meticillin-resistant Staphylococcus aureus (MRSA) accounted for 60.2% of cases. Overall mortality due to S. aureus bacteraemia was 35.1%. Infection due to MRSA, severity of clinical status (severe sepsis or septic shock) and inadequate initial antimicrobial therapy were identified by univariate analysis as predictors of mortality. After Cox regression analysis, severity of clinical manifestations [hazard ratio (HR) 6.86, 95% confidence interval (CI) 3.05-15.43] and inadequacy of antimicrobial therapy (HR 2.27, 95%CI 1.02-5.09) remained as risk factors for mortality. Early diagnosis of bacteraemia should be sought in order to implement adequate treatment before the onset of severe sepsis and septic shock, thus reducing the mortality rate.

Impact of Inadequate Initial Antimicrobial Therapy on Mortality in Infections Due to Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae

Infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) have increased markedly in recent years. Risk factors for mortality among ESBL-EK infections have not been studied. This retrospective cohort study was conducted in a 625-bed tertiary care medical center and a 344-bed urban community hospital to determine whether inadequate initial antimicrobial therapy (IIAT) (>48 hours between the time a culture was obtained and initiation of an agent to which the infecting organism was susceptible) is associated with mortality in ESBL-EK infections. All hospitalized patients with an ESBL-EK infection between June 1, 1997, and December 31, 2002, were eligible for inclusion. Subsequently, we conducted a nested case-control study to identify risk factors for IIAT. Of 187 subjects, 32 (17.1%) died while in the hospital. Clinical site of infection was a significant effect modifier in the association between IIAT and mortality. The presence of IIAT was an independent risk factor for mortality, but only for nonurinary ESBL-EK infections (adjusted odds ratio [95% confidence interval], 10.04 [1.90-52.96]). Independent risk factors for IIAT were (1) infection with a multidrug-resistant ESBL-EK (ie, resistant to sulfamethoxazole-trimethoprim, aminoglycosides, and quinolones) (14.58 [1.91-111.36]) and (2) health care-acquired ESBL-EK infection (4.32 [1.49-12.54]). Inadequate initial antimicrobial therapy is an independent risk factor for mortality in ESBL-EK infections, but only among nonurinary infections. Multidrug resistance was a strong risk factor for IIAT.

Hospital-Acquired Pneumonia in Critically Ill Patients: Factors Associated with Episodes Due to Imipenem-Resistant Organisms

Inadequate initial antimicrobial therapy represents one of the factors associated with mortality of patients suffering from hospital-acquired pneumonia. According to its wide antimicrobial spectrum, imipenem belongs to the usual antibiotics proposed by current guidelines for such a therapy. However, major changes in the antibiotic susceptibility patterns of bacteria in the intensive care unit (ICU) have occurred. Our goal was to determine the incidence of hospital-acquired pneumonia (HAP) due to imipenem-resistant organism(s) in our ICU and to identify factors associated with such a resistance. From January 1994 to December 2001, all consecutive patients admitted to our ICU for HAP or exhibiting HAP during their ICU stay were included in an observational cohort. Patients with a bacteriologically documented HAP were studied. For each causative pathogen, imipenem susceptibility was routinely determined. Patients with an HAP episode due to at least one imipenem-resistant causative organism were compared with patients who developed HAP in which all incriminated pathogens were imipenem susceptible. 235 patients were included in our observational cohort. Among them, 168 had an HAP episode with a bacteriologically proven infection. In 42 patients (25%), at least one causative organism was resistant to imipenem. The 44 imipenem-resistant organisms were Staphylococcus aureus (n = 15), Pseudomonas aeruginosa (n = 14), Stenotrophomonas maltophilia (n = 13), and Acinetobacter baumannii (n = 2). Multivariate analysis identified four significant independent factors associated with resistance of causative organism(s) to imipenem: prior use of a fluoroquinolone (AOR = 3.9; 95% CI: 1.8 to 8.8; p < 0.0001), prior use of an aminoglycoside (AOR = 2.6; CI: 1.2 to 5.9; p = 0.02), use of invasive blood pressure monitoring (AOR = 2.7; CI: 1.0 to 7.0; p = 0.04) and bilateral chest X-ray involvement (AOR = 2.6; CI: 1.1 to 5.8; p = 0.02). Factors associated with potential inadequacy of imipenem used as the single antibiotic for initial empiric treatment for HAP were identified. When they are present, imipenem should be either combined with antibiotics such as vancomycin and ciprofloxacin or replaced with another broad-spectrum antimicrobial regimen.