Inadequate Empiric Antibiotic Therapy Research Articles

Multidrug-Resistant Sepsis: A Critical Healthcare Challenge.

Sepsis globally accounts for an alarming annual toll of 48.9 million cases, resulting in 11 million deaths, and inflicts an economic burden of approximately USD 38 billion on the United States healthcare system. The rise of multidrug-resistant organisms (MDROs) has elevated the urgency surrounding the management of multidrug-resistant (MDR) sepsis, evolving into a critical global health concern. This review aims to provide a comprehensive overview of the current epidemiology of (MDR) sepsis and its associated healthcare challenges, particularly in critically ill hospitalized patients. Highlighted findings demonstrated the complex nature of (MDR) sepsis pathophysiology and the resulting immune responses, which significantly hinder sepsis treatment. Studies also revealed that aging, antibiotic overuse or abuse, inadequate empiric antibiotic therapy, and underlying comorbidities contribute significantly to recurrent sepsis, thereby leading to septic shock, multi-organ failure, and ultimately immune paralysis, which all contribute to high mortality rates among sepsis patients. Moreover, studies confirmed a correlation between elevated readmission rates and an increased risk of cognitive and organ dysfunction among sepsis patients, amplifying hospital-associated costs. To mitigate the impact of sepsis burden, researchers have directed their efforts towards innovative diagnostic methods like point-of-care testing (POCT) devices for rapid, accurate, and particularly bedside detection of sepsis; however, these methods are currently limited to detecting only a few resistance biomarkers, thus warranting further exploration. Numerous interventions have also been introduced to treat MDR sepsis, including combination therapy with antibiotics from two different classes and precision therapy, which involves personalized treatment strategies tailored to individual needs. Finally, addressing MDR-associated healthcare challenges at regional levels based on local pathogen resistance patterns emerges as a critical strategy for effective sepsis treatment and minimizing adverse effects.

Prevalence of Antibiotic-Resistant Pathogens in Culture-Proven Sepsis and Outcomes Associated With Inadequate and Broad-Spectrum Empiric Antibiotic Use

Broad-spectrum antibiotics are recommended for all patients with suspected sepsis to minimize the risk of undertreatment. However, little is known regarding the net prevalence of antibiotic-resistant pathogens across all patients with community-onset sepsis or the outcomes associated with unnecessarily broad empiric treatment. To elucidate the epidemiology of antibiotic-resistant pathogens and the outcomes associated with both undertreatment and overtreatment in patients with culture-positive community-onset sepsis. This cohort study included 17 430 adults admitted to 104 US hospitals between January 2009 and December 2015 with sepsis and positive clinical cultures within 2 days of admission. Data analysis took place from January 2018 to December 2019. Inadequate empiric antibiotic therapy (ie, ≥1 pathogen nonsusceptible to all antibiotics administered on the first or second day of treatment) and unnecessarily broad empiric therapy (ie, active against methicillin-resistant Staphylococcus aureus [MRSA]; vancomycin-resistant Enterococcus [VRE]; ceftriaxone-resistant gram-negative [CTX-RO] organisms, including Pseudomonas aeruginosa; or extended-spectrum β-lactamase [ESBL] gram-negative organisms when none of these were isolated). Prevalence and empiric treatment rates for antibiotic-resistant organisms and associations of inadequate and unnecessarily broad empiric therapy with in-hospital mortality were assessed, adjusting for baseline characteristics and severity of illness. Of 17 430 patients with culture-positive community-onset sepsis (median [interquartile range] age, 69 [57-81] years; 9737 [55.9%] women), 2865 (16.4%) died in the hospital. The most common culture-positive sites were urine (9077 [52.1%]), blood (6968 [40.0%]), and the respiratory tract (2912 [16.7%]). The most common pathogens were Escherichia coli (5873 [33.7%]), S aureus (3706 [21.3%]), and Streptococcus species (2361 [13.5%]). Among 15 183 cases in which all antibiotic-pathogen susceptibility combinations could be calculated, most (12 398 [81.6%]) received adequate empiric antibiotics. Empiric therapy targeted resistant organisms in 11 683 of 17 430 cases (67.0%; primarily vancomycin and anti-Pseudomonal β-lactams), but resistant organisms were uncommon (MRSA, 2045 [11.7%]; CTX-RO, 2278 [13.1%]; VRE, 360 [2.1%]; ESBLs, 133 [0.8%]). The net prevalence for at least 1 resistant gram-positive organism (ie, MRSA or VRE) was 13.6% (2376 patients), and for at least 1 resistant gram-negative organism (ie, CTX-RO, ESBL, or CRE), it was 13.2% (2297 patients). Both inadequate and unnecessarily broad empiric antibiotics were associated with higher mortality after detailed risk adjustment (inadequate empiric antibiotics: odds ratio, 1.19; 95% CI, 1.03-1.37; P = .02; unnecessarily broad empiric antibiotics: odds ratio, 1.22; 95% CI, 1.06-1.40; P = .007). In this study, most patients with community-onset sepsis did not have resistant pathogens, yet broad-spectrum antibiotics were frequently administered. Both inadequate and unnecessarily broad empiric antibiotics were associated with higher mortality. These findings underscore the need for better tests to rapidly identify patients with resistant pathogens and for more judicious use of broad-spectrum antibiotics for empiric sepsis treatment.

Reinventing the wheel: Impact of prolonged antibiotic exposure on multidrug-resistant ventilator-associated pneumonia in trauma patients.

Multidrug-resistant (MDR) strains of both Acinetobacter baumannii (AB) and Pseudomonas aeruginosa (PA) as causative ventilator-associated pneumonia (VAP) pathogens are becoming increasingly common. Still, the risk factors associated with this increased resistance have yet to be elucidated. The purpose of this study was to examine the changing sensitivity patterns of these pathogens over time and determine which risk factors predict MDR in trauma patients with VAP. Patients with either AB or PA VAP over 10 years were stratified by pathogen sensitivity (sensitive [SEN] and MDR), age, severity of shock, and injury severity. Prophylactic and empiric antibiotic days, risk factors for severe VAP, and mortality were compared. Multivariable logistic regression was performed to determine which risk factors were independent predictors of MDR. Three hundred ninety-seven patients were identified with AB or PA VAP. There were 173 episodes of AB (91 SEN and 82 MDR) and 224 episodes of PA (170 SEN and 54 MDR). The incidence of MDR VAP did not change over the study (p = 0.633). Groups were clinically similar with the exception of 24-hour transfusions (14 vs. 19 units, p = 0.009) and extremity Abbreviated Injury Scale (AIS) score (1 vs. 3, p < 0.001), both significantly increased in the MDR group. Antibiotic exposure as well as multiple episodes of inadequate empiric antibiotic therapy (mIEAT) (63% vs. 81%, p < 0.001) were significantly increased in the MDR group. Multivariable logistic regression identified prophylactic antibiotic days (odds ratio, 23.1; 95% confidence interval, 16.7-28, p < 0.001) and mIEAT (odds ratio, 18.1; 95% confidence interval, 12.2-26.1, p = 0.001) as independent predictors of MDR after adjusting for severity of shock, injury severity, severity of VAP, and antibiotic exposure. Prolonged exposure to unnecessary antibiotics remains one of the strongest predictors for the development of antibiotic resistance. Multivariable logistic regression identified prophylactic antibiotic days and mIEAT an independent risk factors for MDR VAP. Thus, limiting prophylactic antibiotic days is the only potentially modifiable risk factor for the development of MDR VAP in trauma patients. Level IV Therapeutic; level III Prognostic.

Antimicrobial resistance in urinary tract infections at a large urban ED: Factors contributing to empiric treatment failure

ObjectiveTo calculate the emergency department (ED)-level Escherichia coli percentage of isolates susceptible to commonly used antibiotics and to determine the risk factors associated with inadequate empiric antibiotic therapy among patients treated for urinary tract infections (UTIs) in our ED. MethodsRetrospective cohort study conducted at a large tertiary teaching hospital. Participants included patients older than 18years of age who had a urine culture with growth of >100,000 colonies of E. coli. Demographic and therapeutic choices associated with inadequate empiric antibiotic therapy were explored. Antimicrobial susceptibility pattern of E. coli isolates recovered from ED patients were calculated, and stratified by gender and age. ResultsA total of 300 unique patients had E. coli bacteriuria during the study period. Among patients who received at least one dose of antibiotic in the ED, variables independently associated with an increased risk of inadequate empiric therapy were age (relative risk [RR] 1.016; 95% confidence interval [CI] 1.001–1.031; P=0.032), male gender (RR 2.507; 95% CI 1.470–4.486; P=0.001), and use of fluoroquinolones (RR 2.128; 95% CI 1.249–3.624 P=0.005). Sub-group analysis of patients discharged from the ED showed that definitive therapy with nitrofurantoin decreased the risk of inadequate empiric antibiotic therapy by 80% (RR 0.202; CI 0.065–0.638; P=0.006). ED-level antibiograms showed differences in antimicrobial susceptibility of E. coli by age and gender. ConclusionsDevelopment of ED-level antimicrobial susceptibility data and consideration of patients' clinical characteristics can help better guide selection of empiric antibiotic therapy for the treatment of UTIs.

Factors associated with suitability of empiric antibiotic therapy in hospitalized patients with bloodstream infections

Background: Bacteremia is associated with high morbidity and mortality rates. Initiation of inadequate empiric antibiotic therapy is associated with a worse outcome. The aim of this study was to establish the prevalence and the factors associated with inappropriate empiric antibiotic therapy in patients hospitalized with bacteremia.Methods: A cross-sectional study was conducted during January 2010–December 2011 at the medical wards of the Chaim Sheba Medical Center, Israel. The records of all patients with bacteremia were reviewed. Clinical and laboratory characteristics, bacteremic pathogens and antimicrobial agents were retrieved from the medical records. Factors associated with appropriateness of empiric antibiotic therapy were assessed.Results: A total of 681 eligible adults were included in the study. Antibiotic therapy was found to be inappropriate in 138 (20.2%) patients (95% C.I. 17.2–23.2). The rate of appropriateness was not related to the type of antibiotic regimen and the type of bacteria. Patients with healthcare-associated infections were more likely to be administrated inappropriate antibiotic therapy. Patients with primary bloodstream infections were also more likely to be administrated inappropriate antibiotic therapy. Empiric combination therapy was more likely to be appropriate than monotherapy, except for an aminoglycosides-based combination.Conclusions: Combination empiric antibiotic therapy should be considered in patients with healthcare-associated infections and in those with primary bloodstream infections.

Antibiotic treatment and mortality in patients with Listeria monocytogenes meningitis or bacteraemia

Invasive Listeria monocytogenes infections carry a high mortality despite antibiotic treatment. The rareness of the infection makes it difficult to improve antibiotic treatment through randomized clinical trials. This observational study investigated clinical features and outcome of invasive L. monocytogenes infections including the efficacy of empiric and definitive antibiotic therapies. Demographic, clinical and biochemical findings, antibiotic treatment and 30-day mortality for all episodes of L. monocytogenes bacteraemia and/or meningitis were collected by retrospective medical record review in the North Denmark Region and the Capital Region of Denmark (17 hospitals) from 1997 to 2012. Risk factors for 30-day all-cause mortality were assessed by logistic regression. The study comprised 229 patients (median age: 71 years), 172 patients had bacteraemia, 24 patients had meningitis and 33 patients had both. Significant risk factors for 30-day mortality were septic shock (OR 3.0, 95% CI 1.4–6.4), altered mental state (OR 3.6, 95% CI 1.7–7.6) and inadequate empiric antibiotic therapy (OR 3.8, 95% CI 1.8–8.1). Cephalosporins accounted for 90% of inadequately treated cases. Adequate definitive antibiotic treatment was administered to 195 patients who survived the early period (benzylpenicillin 72, aminopenicillin 84, meropenem 28, sulfamethoxazole/trimethoprim 6, and piperacillin/tazobactam 5). Definitive antibiotic treatment with benzylpenicillin or aminopenicillin resulted in a lower 30-day mortality in an adjusted analysis compared with meropenem (OR 0.3; 95% CI 0.1–0.8). In conclusion, inadequate empiric antibiotic therapy and definitive therapy with meropenem were both associated with significantly higher 30-day mortality.

Gender disparity in ventilator-associated pneumonia following trauma: identifying risk factors for mortality.

Gender alone offers no survival advantage in humans following trauma. However, male gender does predict increased morbidity, specifically ventilator-associated pneumonia (VAP). Previous work has shown that despite lower incidence of VAP, females with VAP have increased mortality. The purposes of this study were to evaluate the impact of VAP and gender on outcome and to determine which characteristics of severe VAP predict mortality in trauma patients. Patients with VAP (≥10 colony-forming units per milliliter in bronchoalveolar lavage) over 8 years were stratified by gender, age, severity of shock, and injury severity. Severe VAP factors were defined as multiple-episode, polymicrobial, multidrug-resistant, nosocomial VAP diagnosed within 7 days of admission (eNVAP), and multiple inadequate empiric antibiotic therapy episodes. Mortality and severe VAP factors were compared using χ analysis. Multivariable logistic regression (MLR) was performed to determine which VAP factors were independent predictors of mortality. A total of 854 patients were identified, 676 men (79%) and 178 women (21%). Despite a higher incidence of VAP among males (3.8% vs. 2.6%, p = 0.001), mortality was higher in females (24% vs. 15%, p = .009). All characteristics of severe VAP were increased in females except multiple episodes (p = 0.15). MLR identified eNVAP as an independent predictor of mortality in females with severe VAP after adjusting for age, Glasgow Coma Scale (GCS) score, Injury Severity Score (ISS), admission base excess, and 24-hour transfusions (odds ratio, 9.97; p = 0.001). That females develop less VAP but experience increased mortality confirms previous studies. Characteristics of severe VAP are increased in females and may contribute to this observed mortality difference. MLR identified eNVAP as an independent predictor of mortality in females with severe VAP following trauma. Epidemiologic/prognostic study, level III.

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Introduction: Achromobacter species (formerly Alcaligenes) are a rare cause of ventilator-associated pneumonia (VAP). Most cases to date have been in patients with immunocompromised states or chronic comorbidities. No studies of Achromobacter VAP have been published in trauma patients. The purpose of this study is to report the outcomes of critically ill trauma patients with VAP caused by Achromobacter species. Methods: This was a retrospective study of patients admitted to the trauma ICU of the Regional Medical Center at Memphis who had Achromobacter VAP between 1999-2012. Traditional signs and symptoms of VAP triggered a bronchoscopic bronchoalveolar lavage culture. The diagnostic threshold was >100,000 colony forming units/mL. Exclusion criteria were cystic fibrosis, active malignancy, HIV infection or incomplete data. Antibiotic selection and duration of therapy were at the discretion of the trauma team. Clinical and microbiologic success were determined using standard definitions. Results: Twenty eight patients were included (64% male, 37% female). Mean age was 40 years, mean APACHE II score was 29 [8-45] and mean ISS was 40 [16-57]. Unique characteristics compared to a typical VAP population included a long time to diagnosis of VAP (mean 21 days), an extended duration of mechanical ventilation (mean 33 days), a high rate of previous VAP (68%), high incidence of polymicrobial VAP (82%), and long ICU and hospital length of stay (mean 44, 62 days). Monotherapy was utilized in 20 cases (71%). The most commonly used antimicrobial was imipenem (50%). Inadequate empiric antibiotic therapy was common (50%); however, all patients eventually received appropriate treatment. The mean duration of antibiotic therapy was 9 days. The clinical success rate was 89% (25/28), and the microbiologic success rate was 94% (15/16). Of the clinical failures, there was one relapse and two VAP-related deaths. Conclusions: Achromobacter VAP is rare in trauma ICU patients. When it occurs, there is an acceptable clinical and microbiologic success rate.

Risk factors for clinical failure in patients hospitalized with cellulitis and cutaneous abscess

The objective of this study was to evaluate clinical outcomes and risk factors associated with clinical failure in patients hospitalized with cellulitis with or without abscess. We performed a retrospective cohort study among adults admitted for cellulitis/cutaneous abscess from July 1, 2009 through June 30, 2010. Binary univariate and multivariate logistic regression analyses were performed to identify risk factors for clinical failure among evaluable patients. A total of 210 cases met inclusion criteria. Among 106 evaluable cases, clinical failure occurred in 34 (32.1%) patients. Weight over 100 kg (Odds ratio [OR] = 5.20, P = 0.01), body mass index (BMI) ≥40 (OR 4.10, P = 0.02), inadequate empiric antibiotic therapy (OR = 9.25, P < 0.01), recent antimicrobial therapy (OR = 2.98, P = 0.03), and lower end of antibiotic dosing per treatment guidelines upon discharge (OR = 3.64, P < 0.01) were independent risk factors for clinical failure. Further subgroup analysis demonstrated that morbidly obese patients were at higher risk for clinical failure if they were discharged on a low oral dose of clindamycin or trimethoprim/sulfamethoxazole (P = 0.002). Inappropriate antimicrobial selection and dosing may adversely affect clinical outcomes among patients with cellulitis/cutaneous abscess. Obese individuals may be at particular risk for clinical failure secondary to inadequate dosing of antimicrobial therapy.

Clinical and Microbiologic Outcomes in Trauma Patients Treated for Stenotrophomonas maltophilia Ventilator‐Associated Pneumonia

To determine clinical and microbiologic plus clinical success rates in critically ill trauma patients who received treatment for Stenotrophomonas maltophilia ventilator-associated pneumonia (VAP). Retrospective medical record review. Level I trauma intensive care unit of a large academic medical center. A total of 101 patients who developed S. maltophilia VAP between January 1997 and December 2007. Patients' baseline demographic and clinical characteristics, as well as characteristics of their VAP, were documented. The primary study outcome was the rate of clinical success in patients with S. maltophilia VAP; a secondary outcome was microbiologic plus clinical success rate in these patients. Standard definitions were employed to determine these outcomes related to VAP treatment. The study population had higher injury severity scores and a higher rate of traumatic brain injury than is typically observed in the study's intensive care unit. The median time to diagnosis of S. maltophilia VAP was 15 days (interquartile range 11-24 days). Stenotrophomonas maltophilia was the sole organism isolated in 34% of patients; the other patients had polymicrobial VAP. Despite inadequate empiric antibiotic therapy being administered to 97% of the patients, the overall clinical success rate was 87%. The microbiologic plus clinical success rate was 82%. The most common treatments for S. maltophilia VAP were trimethoprim-sulfamethoxazole (77 patients received monotherapy, 9 received combination therapy) and ciprofloxacin (6 patients received monotherapy, 8 received combination therapy); all-cause and VAP-related mortality rates were 13% and 7%, respectively. Critically ill trauma patients with S. maltophilia VAP responded well to therapy despite high rates of inadequate empiric antibiotic administration. Trimethoprim-sulfamethoxazole was the most common therapy, but clinical success rates did not differ significantly based on antibiotic selection. This study adds significantly to the available S. maltophilia VAP outcomes data.

Extended-Spectrum β-Lactamase–Producing Bacterial Infections in Adult Solid Organ Transplant Recipients

Limited research is available evaluating infections due to extended-spectrum β-lactamase (ESBL)-producing organisms in adult recipients of solid organ transplant (SOT). To evaluate clinical response and rate of recurrence of ESBL-producing organisms in 20 SOT recipients. In a retrospective case series, records of adult SOT recipients with an admitting diagnosis of infection and a positive culture for an ESBL-producing organism from January 2003 through August 2006 were reviewed. Twenty patients met inclusion criteria. The median time to infection following transplant was 3.5 years (range 1-23 years). Overall, 85% of the patients received inadequate empiric antibiotic therapy, including ciprofloxacin or piperacillin/tazobactam, to manage their infection. Nineteen patients had clinical resolution; however, 12 patients required at least 1 readmission due to infection recurrence. One patient's death occurred during the study period. The median time to readmission for a recurrence was 41 days (18-455 days). All recurrent infections were caused by the same ESBL-producing pathogen and 10 of 12 (83%) infections occurred at the same site as the initial infection. Among patients with recurrent infections, 75% received inadequate empiric therapy upon readmission. All 12 patients with recurrent infections had successful clinical responses to both initial and recurrent infections. The provision of inadequate empiric therapy for new and recurrent infections due to ESBL-producing pathogens was common in this study population. SOT recipients with a history of infection due to an ESBL-producing organism presenting with a new infection should receive adequate empiric therapy with a carbapenem agent until a definitive diagnosis can be established.

Why can't I prescribe that antibiotic? The role of antimicrobial stewardship programmes in modern medicine

Why can't I prescribe that antibiotic? The role of antimicrobial stewardship programmes in modern medicine

Bacterial epidemiology and antimicrobial resistance in ascitic fluid: A 2-year retrospective study

The bacterial epidemiology of bacterascites and spontaneous bacterial peritonitis is evolving. Four hundred and eleven strains isolated from ascites in cirrhotic patients from 5 French hospitals were isolated in 2006 and 2007. Of these, 114 were definitely associated with spontaneous bacterial peritonitis. The proportion of Gram-positive and Gram-negative agents was quite similar, even after excluding coagulase-negative staphylococci, or when considering only definite spontaneous bacterial peritonitis or community-acquired strains. Staphylococci and Escherichia coli were the most frequent pathogens, but enterococci were also involved in nearly 15% of the cases. Among the E. coli, 28% were intermediate or resistant to amoxicillin+clavulanate, 5.3% expressed cephalosporinases or extended beta-lactamases and 17.3% were intermediate or resistant to fluoroquinolones. Resistance to methicillin was observed in 27% of Staphylococcus aureus. Cefotaxime and amoxicillin-clavulanate remained the most effective 'single' agents, however on less than 70% of isolates. Some combinations (such as cefotaxime+amoxicillin) extended coverage to a further 15% of strains. Since inadequate empiric antibiotic therapy is associated with increased mortality, these combinations may be of great interest as first-line treatment, even though they may also lead to the development of antimicrobial resistance. Repeated epidemiological surveys and new clinical trials are thus needed.

Reduction in Inadequate Empiric Antibiotic Therapy for Ventilator-Associated Pneumonia: Impact of a Unit-Specific Treatment Pathway

Empiric antibiotic therapy is routinely initiated for patients with presumed ventilator-associated pneumonia (VAP). Reported mortality rates for inadequate empiric antibiotic therapy (IEAT) for VAP range from 45 to 91 per cent. The purpose of this study was to determine the effect of a unit-specific pathway for the empiric management of VAP on reducing IEAT episodes and improving outcomes in trauma patients. Patients admitted with VAP over 36-months were identified and stratified by gender, age, severity of shock, and injury severity. Outcomes included number of IEAT episodes, ventilator days, intensive care unit days, hospital days, and mortality. Three hundred and ninety-three patients with 668 VAP episodes were identified. There were 144 (22%) IEAT episodes: significantly reduced compared with our previous study (39%) (P < 0.001). Patients were classified by number of IEAT episodes: 0 (n = 271), 1 (n = 98) and > or = 2 (n = 24). Mortality was 12 per cent, 13 per cent, and 38 per cent (P < 0.001), respectively. Multivariable logistic regression identified multiple IEAT episodes as an independent predictor of mortality (odds ratio = 4.7; 95% confidence interval: 1.684-13.162). Multiple IEAT episodes were also associated with prolonged mechanical ventilation and intensive care unit stay (P < 0.001). Trauma patients with multiple IEAT episodes for VAP have increased morbidity and mortality. Adherence to a unit-specific pathway for the empiric management of VAP reduces multiple IEAT episodes. By limiting IEAT episodes, resource utilization and hospital mortality are significantly decreased.

Infections due to Escherichia coli producing extended-spectrum β-lactamase among hospitalised patients: factors influencing mortality

We performed a retrospective matched-cohort study to determine the risk factors for mortality among patients with Escherichia coli infections. From January 1996 to December 2003, 100 hospitalised patients with extended-spectrum beta-lactamase (ESBL)-producing E. coli infections were compared with patients not infected with ESBL-producing E. coli. These patients were selected according to the same site of infection and the closest date of admission. Comparison of the two groups showed that empirical antibiotic therapy was more often inadequate in patients infected with ESBL-producing E. coli (44% vs 15%; P<0.01), and that early mortality (16% vs 6%; P=0.02) and overall mortality (25% vs 11%; P=0.01) were also significantly higher in patients with ESBL-producing E. coli infections. A multivariate model identified the urinary tract focus as the only independent risk factor influencing early mortality for E. coli infections [odds ratio (OR): 0.1; 95% confidence interval (CI): 0.03-0.7; P=0.01]. All 12 patients with ESBL-producing E. coli urinary tract infections treated initially with an oxyimino-beta-lactam survived. Subsequent analysis of the factors influencing early mortality in the cohort of 130 patients with a non-urinary E. coli infection found inadequate empirical antibiotic therapy as an independent risk factor for mortality only for non-urinary E. coli infections (adjusted OR: 3.0; 95% CI: 1.0-8.6; P=0.03). The study showed that hospitalised patients with ESBL-producing E. coli infections more often receive inadequate empiric antibiotic therapy and have a higher mortality rate than those infected with non-ESBL-producing strains. The site of infection strongly influences mortality. The administration of inadequate empirical antibiotic therapy is independently associated with higher mortality only among patients with non-urinary tract infections.

Mortalidad y factores pronósticos en pacientes hospitalizados por bacteriemia adquirida en la comunidad

Community-acquired bacteremia is a frequently clinical problem and is associated with a high mortality. The Pitt bacteremia score that is calculated using body temperature, mental status, and some respiratory and circulatory features is an useful tool in order to know the prognosis of patients with bacteremia. Objectives were to know microbial etiology of bacteremia in our community, percentage of patients that received an inadequate empiric antibiotic treatment and independent prognostic factors associated with mortality, including Pitt bacteremia score. Observational study of a cohort of patients over 18 years admitted at a tertiary hospital due to an infection with a community-acquired bacteremia. Twenty-eight cases were rejected because possible blood culture contamination. Seventy-five patients were included, the mean age was 68.6 +/- 18.2 years, 38 women (51%). Mortality rate was 23% [IC95% 13.8-33.8]. More frequent bacteria isolated were Escherichia coli, Staphylococcus aureus, coagulase negative staphylococci, Pseudomonas aeruginosa, Streptococcus viridans, enterococci and Klebsiella spp. Mortality in patients treated with an inadequate antibiotic therapy (18%, 3 patients) was not lower than in adequately treated patients (24%, 14 patients, p = 0.42). Independent prognostic factors related to mortality were serum albumin concentration, OR = 5.17 (IC 95% 1.45-16.7) for every downing step of 1 g/dl, the Pitt bacteremia score OR = 1.50 (IC 95% 1.01-2.24) for every unit increase, and a high score at McCabe and Jackson classification OR = 5.08 ( IC 95% 1.43-16.7). An inadequate empiric antibiotic therapy was not associated with a worse vital prognosis. Independent prognostic factors related to mortality were serum albumin concentration, the Pitt bacteremia score, and the McCabe and Jackson classification.

Optimizing Antibiotic-Related Outcomes in the Critically Ill Patient

Whether the focus is on the clinical, microbiologic, or economic aspects of antimicrobial therapy, attention must be directed toward 3 interrelated factors to optimize infection outcomes: the host, the microbe, and the antibiotic. Ignoring any one of these factors is potentially dangerous as it discounts their essential contributions to the potential for a successful clinical response. As with all infectious diseases, aggressive diagnostic procedures, along with early and targeted treatment, are required. This is especially true for critically ill patients in the intensive care unit, such as those with pneumonia or sepsis, because inadequate empiric antibiotic therapy in this population results in increased mortality and infection-related morbidity (eg, length of stay in the intensive care unit, duration of mechanical ventilation, and risk of septic shock and bacteremia). Prescribing the appropriate antibiotic not only requires knowledge of the pathogen and its in vitro susceptibility profile, but also consideration of phamlacodynamics and the likelihood that a chosen dosage regimen will provide optimum bactericidal exposure. This review summarizes current efforts focused on optimizing the selection of initial antimicrobial therapies in an attempt to minimize the potential for poor outcomes in the critically ill infected patient.

Effect From Multiple Episodes of Inadequate Empiric Antibiotic Therapy for Ventilator-Associated Pneumonia on Morbidity and Mortality Among Critically Ill Trauma Patients

Empiric antibiotic therapy is routinely initiated for patients with presumed ventilator-associated pneumonia (VAP). The impact of inadequate empiric antibiotic therapy (IEAT) may vary among critically ill populations. The purpose of this retrospective study was to determine the effect of IEAT on the outcome for adult trauma patients with VAP. This study enrolled 82 patients with multiple VAP episodes (200 VAP episodes; mean, 2.4 +/- 0.65 per patient; range, 2-5 episodes). An episode of IEAT was a VAP episode with empiric therapy having no in vitro activity against causative bacteria. Overall, there were 78 (39%) IEAT episodes involving 54 patients. Most often, IEAT was attributable to the presence of Acinetobacter spp, Stenotrophomonas maltophilia, or Alcaligenes xylosoxidans. All the patients received appropriate definitive therapy according to the final culture. The patients were classified by number of IEAT episodes: 0 (n = 28), 1 (n = 34), and more than 1 (n = 20). Demographics and injury severity were similar among the groups. The mortality rate was 3.6% for no episodes, 8.8% for one episode, and 45% for more than one episode (p < 0.001). On the basis of multiple logistic regression, experiencing multiple IEAT episodes was independently associated with the risk of death (odds ratio, 4.28; 95% confidence interval, 1.44-12.71). Additionally, experiencing multiple IEAT episodes was associated with prolonged intensive care unit stay (p = 0.007) and prolonged mechanical ventilation (p = 0.005). Critically ill trauma patients experiencing multiple episodes of IEAT for VAP have increased morbidity and mortality. These findings reinforce the importance of developing and refining a unit-specific pathway for the empiric management of VAP.

Risk factors for late-onset nosocomial pneumonia caused by Stenotrophomonas maltophilia in critically ill trauma patients.

Patients with nosocomial pneumonia caused by Stenotrophomonas maltophilia often receive inadequate empiric antibiotic therapy, potentially increasing mortality. Knowledge of the risk factors associated with S. maltophilia pneumonia may better guide the selection of empiric antibiotic therapy. Potential risk factors for S. maltophilia pneumonia were retrospectively analyzed for critically ill trauma patients with late-onset gram-negative pneumonia. The effects of S. maltophilia infection and inadequate empiric antibiotic therapy on patient outcomes were also assessed. By multivariate analysis, S. maltophilia pneumonia was found to be associated with cefepime exposure and tracheostomy in patients with a single pneumonia episode and with higher Injury Severity Score and pulmonary contusion in patients with multiple pneumonia episodes. S. maltophilia pneumonia was associated with increased patient morbidity; only inadequate empiric antibiotic therapy was associated with a higher mortality rate. In critically ill trauma patients with late-onset ventilator-associated pneumonia and these risk factors, empiric antibiotic therapy should include agents active against S. maltophilia.