Adequate Empirical Antimicrobial Therapy Research Articles

Development of polyresistance in microorganisms during antibiotic therapy in a multidisciplinary hospital during a pandemic COVID-19

Background. Irrational and excessive use of antimicrobials drugs (AMD) creates conditions for the development of a global crisis of health systems around the world associated with antibiotic resistance.
 Aim. To conduct a retrospective study of the impact of the use of AMD on the change in the microbiological landscape and the sensitivity of microorganisms in the conditions of pandemic of the new coronavirus infection (COVID-19) in 2020–2021 in intensive care departments (ICD) of a multidisciplinary hospital.
 Materials and methods. In the course of the work, strains of microorganisms isolated from patients and from the surfaces of the hospital environment and changes in their sensitivity to significant groups of AMD in ICD for somatic and infectious patients with COVID-19 were compared. The sensitivity of the isolates was evaluated in accordance with the criteria of requirements of European Committee on Antimicrobial Susceptibility Testing – EUCAST, version 10.0, 2020.
 Results. A total of 1,394 isolates were studied, including 1,379 clinical and 15 isolates from the surfaces of the hospital environment. It was found that in all ICD in 2020–2021, gram-negative microorganisms prevailed in infectious loci in 70% of cases or more. In 2021, in the ICD in infectious patients with COVID-19, the persistent dominance of the Acinetobacter baumannii microorganism was revealed with an increase in the number of poly- and pan-resistant strains – 48.7%. While in the ICD for somatic patients Klebsiella Pneumoniae prevailed among gram-negative microorganisms – 37.5% in 2020 and 43.7% in 2021. It has been shown that in one department or in adjacent departments of the same medical institution, various nosocomial microorganisms with an unequal set of resistance genes and sensitivity to AMD may appear over time.
 Conclusion. The necessity of conducting constant microbiological monitoring and a passport of the medical department with mandatory registration of not only isolated strains of microorganisms, but also resistance genes in order to optimize the appointment of timely adequate empirical antimicrobial therapy is substantiated. The period of the latter should be as short as possible, and confirmed by convincing clinical signs of bacterial infection, and subsequently by the isolation of nosocomial flora from the biomaterial of critical loci from patients.

Determinants of Inadequate Empiric Antimicrobial Therapy in ICU Sepsis Patients in Al-Madinah Al-Munawwarah, Saudi Arabia: A Comparison of Artificial Neural Network and Regression Analysis.

In the management of sepsis, providing adequate empiric antimicrobial therapy is one of the most important pillars of sepsis management. Therefore, it is important to evaluate the adequacy of empiric antimicrobial therapy (EAMT) in sepsis patients admitted to intensive care units (ICU) and to identify the determinants of inadequate EAMT. The aim of this study was to evaluate the adequacy of empiric antimicrobial therapy in patients admitted to the ICU with sepsis or septic shock, and the determinants of inadequate EAMT. The data of patients admitted to the ICU units due to sepsis or septic shock in two tertiary healthcare facilities in Al-Madinah Al-Munawwarah were retrospectively reviewed. The current study used logistic regression analysis and artificial neural network (ANN) analysis to identify determinants of inadequate empiric antimicrobial therapy, and evaluated the performance of these two approaches in predicting the inadequacy of EAMT. The findings of this study showed that fifty-three per cent of patients received inadequate EAMT. Determinants for inadequate EAMT were APACHE II score, multidrug-resistance organism (MDRO) infections, surgical history (lower limb amputation), and comorbidity (coronary artery disease). ANN performed as well as or better than logistic regression in predicating inadequate EAMT, as the receiver operating characteristic area under the curve (ROC-AUC) of the ANN model was higher when compared with the logistic regression model (LRM): 0.895 vs. 0.854. In addition, the ANN model performed better than LRM in predicting inadequate EAMT in terms of classification accuracy. In addition, ANN analysis revealed that the most important determinants of EAMT adequacy were the APACHE II score and MDRO. In conclusion, more than half of the patients received inadequate EAMT. Determinants of inadequate EAMT were APACHE II score, MDRO infections, comorbidity, and surgical history. This provides valuable inputs to improve the prescription of empiric antimicrobials in Saudi Arabia going forward. In addition, our study demonstrated the potential utility of applying artificial neural network analysis in the prediction of outcomes in healthcare research.

The Biofire® Filmarray® Pneumonia Plus panel for management of lower respiratory tract infection in mechanically-ventilated patients in the COVID-19 era: a diagnostic and cost-benefit evaluation

We assessed the diagnostic performance of the Biofire® Filmarray® Pneumonia Plus panel (FA-PP) compared to standard culture in Intensive Care Unit patients with suspected ventilator-associated lower respiratory tract infection in the COVID-19 era. We determined whether its implementation in routine diagnostic algorithms would be cost-beneficial from a hospital perspective. Of 163 specimens, 96 (59%) returned negative results with FA-PP and conventional culture, and 29 specimens (17.8%) were positive with both diagnostic methods and yielded concordant qualitative bacterial identification/isolation. Thirty-nine specimens (23.9%) gave discordant results (positive via FA-PP and negative via culture). Real-life adjustments of empirical antimicrobial therapy (EAT) after FA-PP results resulted in additional costs beyond EAT alone of 1868.7 €. Adequate EAT adjustments upon FA-PP results would have resulted in a saving of 6675.8 €. In conclusion, the data presented supports the potential utility of FA-PP for early EAT adjustment in patients with ventilator-associated lower respiratory tract infection.

Catheter-related bloodstream infection management in patients receiving home parenteral nutrition: An observational cohort study

Patients with intestinal failure receiving home parenteral nutrition (HPN) are susceptible to central-line associated bloodstream infections (CLABSIs), with crucial roles for adequate (empiric) antimicrobial therapy and effective catheter management strategies. Our aim was to link recent epidemiologic CLABSI data with clinical outcomes and to identify risk factors for therapeutic failure to decide on the safest and most accurate CLABSI management in patients receiving HPN. A retrospective observational cohort study was conducted. All data on CLABSIs (period 2010-2020) in adult patients receiving HPN were retrieved. The efficacy of attempted catheter salvage and empiric antimicrobial treatment (β-lactam antibiotics) in our center, with a low prevalence of methicillin-resistant staphylococci, was investigated. Multivariate cox-regression analysis was performed to identify risk factors for recurrent CLABSI. 389 CLABSIs occurred in 149 patients. The overall infection rate was 0.64 per 1000 central venous catheter (CVC) days. Most CLABSIs were caused by Coagulase-negative staphylococci (37%). Attempted CVC salvage was successful in 70% of the cases. Empiric antimicrobial therapy was found to be adequate in only 47% of cases, mainly because of insufficient Coagulase-negative staphylococci coverage. According to the Cox model, patients with a replaced CVC had a 50% lower risk of a new CLABSI than patients with a retained (salvaged) CVC during follow-up (HR 0.50; 95% CI 0.35-0.72, P<0.001). CVC salvage can be achieved in most CLABSI cases but seems associated with a shorter CLABSI-free survival. Importantly, based on our findings, a glycopeptide containing antibiotic treatment regimen will increase the likelihood of adequate empiric coverage.

Clinical relevance of Clostridium bacteremia: An 8-year retrospective study

Clostridium spp. are recovered from 25% of the blood culture positive with anaerobes. However, the clinical relevance of Clostridium bacteremia has been controverted in the literature, particularly for C. perfringens. We aimed to evaluate the clinical relevance of Clostridium bacteremia, either due to C. perfringens or other Clostridium species, and to identify the risk factors of mortality in these patients. A retrospective cohort study was conducted from January 2010 to April 2018. All the patients with at least one blood culture positive with any Clostridium species were included. Eighty-one patients with a least one blood culture positive with any Clostridium species were included. Seventy patients (86.4%) fulfilled the criteria for clinically relevant bacteremia. Bacteremia due to C. perfringens tended to be less clinically relevant than other Clostridium species but this was not statistically significant (76% vs 91.2%, P = 0.09). In case of clinically relevant bacteremia, the 30-day mortality rate was 31.4%. In multivariate analysis, adequate empiric antimicrobial therapy was significantly associated with survival (P = 0.03). In conclusion, bacteremia due to C. perfringens or other Clostridium species is usually clinically relevant. This finding was also supported by an improved survival at 30 days when adequate empiric antimicrobial therapy was administered.

Accelerating Initiation of Adequate Antimicrobial Therapy Using Real-Time Decision Support and Microarray Testing.

Introduction:Bloodstream infections (BSI) represent a common cause of sepsis and mortality in children. Early and adequate empirical antimicrobial therapy is a critical component of successful treatment of BSI. Rapid PCR-based diagnostic technologies, such as nucleic acid microarrays, can decrease the time needed to identify pathogens and antimicrobial resistance and have the potential to ensure patients are started on adequate antibiotics as early as possible. However, without appropriate processes to support timely and targeted interpretation of these results, these advantages may not be realized in practice.Methods:Our Antimicrobial Stewardship Program (ASP) implemented a quality improvement initiative using the Institute for Healthcare Improvement’s Model for Improvement to decrease the time between a nucleic acid microarray result for Gram-positive bacteremia and the time a patient was placed on adequate antimicrobial therapy. The primary effective intervention was a near real-time notification system to the managing physicians of inadequate antimicrobial therapy via a call from the ASP team.Results:Following the intervention, the average time to adequate antimicrobial therapy in patients with Gram-positive BSI and inadequate coverage decreased from 38 hours with the nucleic acid microarray result alone to 4.7 hours when results were combined with an ASP clinical decision support intervention, an 87% reduction.Conclusions:The positive effects of rapid-detection technologies to improve patient care are enhanced when combined with clinical decision support tools that can target inadequate antimicrobial treatments in near real time.

Inadequate empiric antimicrobial therapy and mortality in geriatric patients with bloodstream infection: A target for antimicrobial stewardship.

Bloodstream infections are responsible for a large proportion of deaths among geriatric patients. Japan is a rapidly aging society; however, little is known about the epidemiology of bloodstream infections in geriatric patients in Japanese institutions. We conducted a retrospective cohort study of patients aged ≥65 years old with a bloodstream infection in a Japanese tertiary care hospital in 2013. We defined inadequate empiric antimicrobial therapy as either antimicrobial treatment that was ineffective against subsequently isolated organisms or treatment initiated after notification of a positive culture. Predictors of inadequate antimicrobial therapy and 30-day mortality among geriatric patients with bloodstream infections were evaluated. We identified 275 patients with a bloodstream infection, of which 42.2% of cases (116/275) were healthcare-associated, hospital-onset. The most common source of bloodstream infection was hepatobiliary (28.0%). Inadequate empiric antimicrobial therapy occurred in 29.8% of the patients. Factors associated with inadequate empiric therapy included a history of surgery prior to bloodstream infection during index hospitalization (adjusted odds ratio [aOR] 3.27; 95% confidence interval [CI] 1.18-9.12). In 275 patients, 38 (13.8%) died within 30 days after the first positive blood culture. Predictors of 30-day mortality was Pitt bacteremia score >6 (aOR 9.80; 95% CI 4.72-20.36). Inadequate empiric antimicrobial therapy occurred in approximately one-third of episodes of bloodstream infection in geriatric patients. Severity at the time of bloodstream infection was likely to have contributed to mortality. The initiation of adequate empiric antimicrobial therapy may have important implications for antimicrobial stewardship even in the elderly population.

Epidemiology and Risk Factors for Isolation of Multi-Drug-Resistant Organisms in Patients with Complicated Intra-Abdominal Infections.

Patients with complicated intra-abdominal infections (cIAIs) caused by multi-drug-resistant organisms (MDROs) have been identified as being at increased risk for adverse outcomes. Prompt identification and stratification of these patients is essential in the clinical management, allowing the physician timely optimization of empiric antimicrobial therapy while awaiting results of intra-operative cultures to streamline antibiotic treatment. The study is a secondary analysis from two prospective multi-center color surveillance studies. It included all consecutively hospitalized adult patients undergoing surgical procedures, interventional drainage, or conservative treatment with cIAIs, with positive cultures performer on intra-operative samples of peritoneal fluid or purulent exudate/discrete abscesses. Patients with pancreatitis and primary peritonitis were excluded. A case-control approach has been used to evaluate the factors associated with the isolation of a MDRO in enrolled patients. Among 1986 patients included in the study, a total of 3534 micro-organisms were isolated from intra-peritoneal fluid samples; in 46.5% of cultures, two or more pathogens were identified. The MDROs represented 9.8% of the total of isolated micro-organisms. The overall incidence rate of MDROs was 13.9%. The MDROs were more frequently isolated in patients with health-care-associated cIAIs (25.4%). Multi-nomial logistic regression analysis of risk factors demonstrated that statistically significant risk factors independently associated with the occurrence of MDROs were previous antimicrobial therapy administered within seven days before operation, presence of severe cardiovascular disease, white blood cell count <4000/mL or >12,000/mL, cIAI acquired in a healthcare setting, and inadequate source control. The study showed that knowledge of five easily recognizable variables-assessable on hospital admission or as soon as the surgical intervention is concluded-might guide the surgeon to identify patients with cIAIs caused by MDROs, and therefore to choose the most adequate empiric antimicrobial therapy for them.

30-day readmission, antibiotics costs and costs of delay to adequate treatment of Enterobacteriaceae UTI, pneumonia, and sepsis: a retrospective cohort study

BackgroundEnterobacteriaceae are common pathogens in pneumonia, sepsis and urinary tract infection (UTI). Though rare, carbapenem resistance (CRE) among these organisms complicates efforts to ensure adequate empiric antimicrobial therapy. In turn this negatively impacts such outcomes as mortality and hospital costs. We explored proportion of total costs represented by antibiotics, 30-day readmission rates, and per-day costs of inadequate antimicrobial coverage among patients with Enterobacteriaceae pneumonia, sepsis and/or UTI in the context of inappropriate (IET) vs. appropriate empiric (non-IET) therapy and carbapenem resistance (CRE) vs. susceptibility (CSE).MethodsWe conducted a retrospective cohort study in the Premier Research database (2009–2013) of 175 US hospitals. We included all adult patients admitted with a culture-confirmed UTI, pneumonia, or sepsis as principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure. Patients with hospital acquired infections or transfers from other acute facilities were excluded. IET was defined as failure to administer an antibiotic therapy in vitro active against the culture-confirmed pathogen within 2 days of admission.ResultsAmong 40,137 patients with Enterobacteriaceae infections (54.2% UTI), 4984 (13.2%) received IET. CRE (3.1%) was more frequent in patients given IET (13.0%) than non-IET (1.6%, p < 0.001). The proportions of total costs represented by antibiotics were similar in IET and non-IET (3.3% vs. 3.4%, p = 0.01), and higher among the group with CRE than CSE (4.2% vs. 3.4%, p < 0.001). The 30-day readmission rates were higher in both IET than non-IET (25.6% vs. 21.1%, p < 0.001) and CRE than CSE (29.7% vs. 21.5%, p < 0.001) groups. Each additional day of inadequate therapy cost an additional $766 (95% CI $661, $870, p < 0.001) relative to adequate treatment.ConclusionsIn this large US cohort of Enterobacteriaceae infections, the cost of antibiotics was a small component of total costs, irrespective of whether empiric treatment was appropriate or whether a CRE was isolated. In contrast, each extra day of inadequate treatment added >$750 to hospital costs. Both CRE and IET were associated with an increased risk of readmission within 30 days.

Antibiotic resistance evaluation and clinical analysis of acute appendicitis; report of 1431 consecutive worldwide patients: A cohort study

BackgroundAcute appendicitis (AA) is one of the most common diseases affecting especially young but also older people. A systematic evaluation of bacteriology of AA has been frequently conducted in children but is not well known and discussed in adult population. Study designThe study has been obtained from two multicenter prospective observational studies (CIAO and CIAOW studies). The aim of the study is to analyze the intra-abdominal bacteriology in AA and its relation with clinical outcomes. ResultsPatients included were 1431, 806 male (56.3%). The mean/median age was 38.9 (SD ± 18.4) and 35 (range 18–94). Clinical condition at the admission was sepsis in 623 patients (43.5%), severe sepsis and septic shock in 29 (2%) and 10 (0.7%). Peritonitis was localized in 1107 patients (77.4%) and generalized in 324 (22.6%). Adequate source-control and empirical antimicrobial therapy were reported in 95.2% and 88.7% of the patients. 47 isolated bacteria (6.8%) were resistant. Two (4.2%) were health-care-associated infections and 45 (95.7%) were community-acquired infections. Univariate analysis showed factor associated to resistant bacteria was the inadequacy of the empiric antimicrobial therapy (p = 0.013); at multivariated analysis factors associated with mortality were age>70 years (p = 0.003) and severe sepsis at the admission (p = 0.02); factors associated to ICU admission were: severe sepsis (p < 0.0001), generalized peritonitis (p < 0.0001), malignancy (p < 0.0001) and cardiovascular disease (p < 0.0001). ConclusionThe evolution of antimicrobial resistance, in common community-acquired infections, combined with lack of new antibiotics development are strictly linked to clinical outcomes. Adequate empirical antimicrobial therapy is fundamental to counteract bacterial resistance.

Antibiotic resistance pattern and clinical outcomes in acute cholecystitis: 567 consecutive worldwide patients in a prospective cohort study

IntroductionPostoperative complications for cholecystitis and cholelithiasis are important causes of intra-abdominal infections (IAIs). There have been no previous reports on intra-abdominal bacteriology in complicated IAIs due to acute cholecystitis (AC). Material and methodsThe data came from two prospective multicenter observational cohort studies (CIAO: the “Complicated Intra-Abdominal infection Observational” study and CIAOW: the “Complicated Intra-Abdominal infection Observational World” study) which involved 116 medical institutions worldwide with consecutive patients who underwent surgery, interventional drainage or conservative treatment for AC. ResultsOf 567 patients, there were 291 males (51.3%). The mean and median age were 62.5 and 64 years respectively. 546 (96.3%) had community-acquired and 21 (3.7%) patients had health-care-associated infections. 267 bacteria were isolated, 21 (7.8%) were resistant bacteria. No resistant Fungi or Anaerobes were isolated. 4 out of the 21 resistant bacteria were health-care-associated. Multivariate analysis demonstrated health-care associated infection (p = 0.03), inadequacy of empiric antimicrobial therapy (p = 0.003) and recent antimicrobial therapy (p < 0.0001) to be factors associated with resistant bacteria. The factors associated with mortality were presence of generalized peritonitis (p < 0.0001) and inadequate source control (p = 0.018). The factors associated with ICU admission were severe sepsis (p < 0.0001), generalized peritonitis (p = 0.001), concomitant malignancy (p = 0.037), inadequate source control (p = 0.025), delay in initial intervention (p < 0.0001) and age over 70 years (p = 0.025). ConclusionThe number of infection caused by Extended Spectrum Beta-Lactamase bacteria (ESBL+) and Klebsiella pneumoniae Carbapenemase-producer bacteria (KPC+) were common in acute cholecystitis and in community-acquired infections. An adequate empirical antimicrobial therapy was fundamental to reduce bacterial resistance and to improve outcomes.

Nosocomial Gram-negative bacteremia in intensive care: epidemiology, antimicrobial susceptibilities, and outcomes

To describe the epidemiology, antimicrobial susceptibilities, treatment, and outcomes of intensive care unit (ICU)-acquired Gram-negative bacteremia. Patients with ICU-acquired Gram-negative bacteremia from 2004 to 2012 were reviewed retrospectively. Independent predictors of mortality were examined using multivariable Cox regression. Seventy-eight cases of ICU-acquired Gram-negative bacteremia occurred in 74 patients. The infection rate was 0.97/1000 patient-days. Mean patient age was 55 years, 62% were male. The most common admission diagnoses were respiratory failure (34%) and sepsis/septic shock (45%). Mortality was 35% at 30 days. The most common source of bacteremia was pneumonia (33%). Of 83 Gram-negative isolates, Escherichia coli (20%) and Pseudomonas aeruginosa (18%) were most common. For aerobic isolates, susceptibilities to ciprofloxacin (61%) and piperacillin/tazobactam (68%) were low. For pseudomonal isolates, susceptibilities to ciprofloxacin (53%), piperacillin/tazobactam (67%), and imipenem (53%) were equally disappointing. Adequate empiric antimicrobial therapy was prescribed in 85% of bacteremia cases. On multivariable analysis, adequate empiric therapy (adjusted hazard ratio (aHR) 0.38, 95% confidence interval (CI) 0.16-0.89), immune suppression (aHR 3.4, 95% CI 1.4-8.3), and coronary artery disease (aHR 4.5, 95% CI 1.7-11.9) were independently associated with 30-day mortality. ICU-acquired Gram-negative bacteremia is associated with high mortality. Resistance to ciprofloxacin, piperacillin/tazobactam, and carbapenems was common. Coronary artery disease, immune suppression, and inadequate empiric antimicrobial therapy were independently associated with increased mortality.

A retrospective study of septic arthritis in a tertiary hospital in West Texas with high rates of methicillin-resistant Staphylococcus aureus infection.

Septic arthritis is an important concern for rheumatologists in the evaluation of joint disease. Very few studies have addressed the microbiologic epidemiology and outcomes of septic arthritis in the USA since the year 2000. We performed a retrospective study of septic arthritis in a tertiary hospital in West Texas from the year 2000 to 2013. We recorded data on patient demographics, microbiologic etiology, treatment patterns, and outcomes. The most common causative organisms were Staphylococcus aureus and Streptococcus spp. Methicillin-resistant Staphylococcus aureus (MRSA) caused septic arthritis in 22.6% of the cases. MRSA septic arthritis was associated with low rates of adequate empiric antimicrobial therapy. The mortality due to sepsis in our study was 5.5%. Patients with septic arthritis had a mean length of stay of 13.5±12.1days and required 2.1±1.4 joint operations. Many patients (29.2%) had readmissions due to complications, and these patients had high rates of home health utilization and transfers to other facilities post hospital discharge. In our logistic regression analysis model, factors associated with poor outcomes in septic arthritis were MRSA, older age, and prosthetic joint infection. Septic arthritis is associated with significant mortality, morbidity, and health care costs, and more studies are needed to improve outcomes, especially considering the increasing rates of MRSA as the pathogen.

Microbial pathogens in moderate to severe diabetic foot infections

Foot infections are the most common complications in diabetic patients and common cause of morbidity and mortality. They require prompt diagnosis and involvement of a multidisciplinary team in their treatment. Prospective study to define the etiology of the deep diabetic foot infections and its specific characteristics concerning the adequate empiric antimicrobial therapy was done. The study included 50 patients, who underwent minor amputations due to moderate to severe infection of the foot. All specimens for microbiology testing were taken by biopsy or aspiration during surgery. Specimens cultivation, identification of the isolated microorganisms and their susceptibility towards antimicrobial agents were performed by conventional methods and automated systems. Diabetic foot infections were predominantly polymicrobial; 42 (84%) of the cases, caused by associations between two, three and four different pathogens. Mixed infections caused by aerobic and anaerobic bacteria were found in 17 patients (34%). Gram-positive bacteria were the prominent microbial pathogens in both monobacterial and polymicrobial infection; mostly Streptococcus agalactiae and Staphylococcus aureus. Gram-negative aerobic bacteria presented 33.3% of all isolated bacteria, predominantly members of Enterobacteriaceae family. Obligate anaerobes represents 16.66% of all isolated bacteria and were causative organisms in 17 (34%) of the patients, more than the other Bacteroides fragilis group and anaerobic streptococci. The strains isolated were susceptible to the recommended antibacterial agents for treatment of moderate and severe diabetic foot infections (DFIs). The optimal approach to DFIs requires immediate surgical intervention, revascularization in the setting of a multisegment vascular lesions, microbiological examination of suitable clinical materials and appropriate antibacterial therapy for empiric treatment of aerobic and anaerobic pathogens Key words: Diabetic foot, infection, microbial pathogens.

Predictive scoring model of mortality in Gram-negative bloodstream infection

AbstractMortality is a well-recognized complication of Gram-negative bloodstream infection (BSI). The aim of this study was to develop a model to predict mortality in patients with Gram-negative BSI by using the Pitt bacteraemia score (PBS) and other clinical and laboratory variables. A cohort of 683 unique adult patients who were followed for at least 28 days after admission to Mayo Clinic Hospitals with Gram-negative BSI from 1 January 2001 to 31 October 2006 and who received clinically predefined appropriate empirical antimicrobial therapy was retrospectively identified. Multivariable logistic regression was used to identify independent risk factors for 28-day all-cause mortality. Regression coefficients from a multivariable model were used to develop a risk score to predict mortality following Gram-negative BSI. Malignancy (OR 3.48, 95% CI 1.94–6.22), liver cirrhosis (OR 5.42, 95% CI 2.52–11.65), source of BSI other than urinary tract or central venous catheter infection (OR 5.54, 95% CI 2.42–12.69), and PBS (OR 1.98, 95% CI 0.92–4.25 for PBS of 2–3 and OR 6.42, 95% CI 3.11–13.24 for PBS ≥ 4) were identified as independent risk factors for 28-day mortality in patients with Gram-negative BSI. A risk-score model was created by adding points for each independent risk factor, and had a c-statistic of 0.84. Patients with risk scores of 0, 4, 8, 12 and 16 had estimated 28-day mortality rates of approximately 0%, 3%, 14%, 45%, and 81%, respectively. The Gram-negative BSI risk score described herein estimated mortality risk with high discrimination in patients with Gram-negative BSI who received clinically adequate empirical antimicrobial therapy.

Impact of multidrug resistance on Pseudomonas aeruginosa ventilator-associated pneumonia outcome: predictors of early and crude mortality

The prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa has increased over the past decade and a significant rise in these isolates in ventilator-associated pneumonia (VAP) has been observed. However, the impact of MDR on VAP outcome has not been analysed in depth. We investigated the risk factors for early and crude mortality in a retrospective study of microbiologically and clinically documented VAP. Ninety-one VAP episodes in 83 patients were included, 31 caused by susceptible P. aeruginosa and 60 by MDR strains, of which 42 (70 %) were extensively drug-resistant (XDR) P. aeruginosa. Thirteen episodes concomitantly presented P. aeruginosa bacteraemia, in seven of which the origin was the respiratory tract. Whereas susceptible P. aeruginosa episodes were more likely than MDR episodes to receive adequate empirical (68 % vs. 30 %; p < 0.001) and definitive antimicrobial therapy (96 % vs. 50 %; p < 0.001), susceptible P. aeruginosa VAP presented a trend towards early mortality (29 % vs. 15 %; p = 0.06). A logistic regression model with early mortality as the dependent variable identified multiorgan dysfunction syndrome (MODS) [odds ratio (OR) 10.4; 95 % confidence interval (CI) 1.7-63.5; p = 0.01] and inadequate antibiotic therapy (OR 4.27; 95 % CI 0.98-18.4; p = 0.052) as independent risk factors for early mortality. A similar analysis identified MODS (OR 4.31; 95 % CI 1.14-16.2; p = 0.03) as the only independent predictor of crude mortality. The severity of acute illness clinical presentation was the main predictor of mortality. Despite adequate antibiotic therapy, susceptible P. aeruginosa seems to cause major early mortality. Although adequate therapy is essential to treat VAP, the severity of acute illness is a more important factor than drug resistance.

Meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia in Tampere University Hospital: a case-control study, Finland October 2002 to January 2010

Meticillin-resistant Staphylococcus aureus (MRSA) has emerged as a frequent pathogen in blood cultures in Pirkanmaa Hospital District (HD), Finland. To study risk factors for MRSA bacteraemia and the adequacy of empirical antimicrobial treatment, we retrospectively reviewed the hospital records of 102 patients, 51 with MRSA, and 51 with meticillin-sensitive Staphylococcus aureus (MSSA) bacteraemias respectively, who had been admitted to Tampere University Hospital in Pirkanmaa HD, from October 2002 to January 2010. For each patient with MRSA bacteraemia, one consecutively detected unmatched patient with MSSA bacteraemia was chosen as control. Patients with MRSA bacteraemias were significantly older (median age: 73 years vs 59 years, p=0.001), were more likely to have been transferred directly from another healthcare facility or were already in the hospital at the onset of bacteraemia (39/51 vs 26/51, p=0.007) and had a higher McCabe class than patients with MSSA bacteraemia (p=0.005). Patients with MRSA bacteraemia more seldom received adequate empirical antimicrobial therapy when compared to those with MSSA bacteraemia (13/51 vs 43/51, p<0.001). Of previously known MRSA carriers 10 of 29 received adequate empirical antimicrobial therapy for their condition. The percentage of MRSA bacteraemias among all S. aureus bacteraemias in Pirkanmaa HD is high compared to corresponding figures for the whole of Finland.

Pseudomonas aeruginosa bacteremia upon hospital admission: risk factors for mortality and influence of inadequate empirical antimicrobial therapy

Pseudomonas aeruginosa is an uncommon cause of bacteremia upon hospital admission (UHA) and the chosen empirical antimicrobial therapy may not cover it appropriately. In a multicenter prospective study conducted in Israel, we evaluated risk factors for in-hospital mortality in patients with P. aeruginosa bacteremia UHA and determined the influence of delay in adequate empirical antimicrobial therapy on patients' outcome. Seventy-six adult patients with P. aeruginosa bacteremia within 72 h of hospital admission were included. Demographic, clinical, and treatment data were collected. Microbiological adequacy of empirical therapy was determined. Severe sepsis or septic shock at admission (OR, 21.9; P < 0.001), respiratory or unknown sources of bacteremia (OR, 11.5; P = 0.003), recent hospitalization (OR, 6.2; P = 0.032), and poor functional status (OR, 5.8; P = 0.029) were identified as independent predictors of mortality. Inadequate empirical antimicrobial therapy was marginally associated with increased mortality only among patients who presented with severe sepsis or septic shock ( P = 0.051).

Campylobacter Bacteremia

Campylobacter is a very rare cause of bloodstream infection, although it has been found relatively frequently in patients infected with human immunodeficiency virus (HIV). The impact of highly active antiretroviral therapy (HAART) and new forms of immunosuppression on the incidence of Campylobacter bacteremia has not been sufficiently assessed. In this study we analyzed the incidence and microbiologic and clinical characteristics of Campylobacter bacteremia over 23 years.We reviewed the clinical records of all patients who had Campylobacter bacteremia from 1985 to 2007. Available strains were reidentified using universal polymerase chain reaction (PCR).During the study period, there were 71 episodes of Campylobacter bacteremia in 63 patients (0.24% of all bloodstream infections), and the incidence remained stable (mean, 0.06/1000 admissions per year and 0.47/100,000 inhabitants per year). Median age was 52 years (interquartile range, 31.25-72.5 yr), and 82% of patients were male. The underlying conditions included liver disease (21/64, 32.8%), HIV infection (15/64, 23.4%), malignancy (7/64, 10.9%), solid organ transplantation (2/64, 3%), hypogammaglobulinemia (10/64, 15.6%), and other (18/64, 31.2%). Twelve patients shared more than 1 underlying condition. Campylobacter bacteremia was community acquired in 81% of the episodes. The origin of the bloodstream infection was abdominal (43.5%), primary (26%), or extraintestinal (31%: respiratory 15%, cellulitis 4.8%, urinary 8%, other 3%). C jejuni was recovered in 66% of cases, C fetus in 19%, and C coli in 12%.Universal PCR was performed on 14 available strains. Molecular and conventional identification matched in 8 isolates. In contrast, molecular methods classified as C fetus (n = 2) and C jejuni (n = 1) 3 strains formerly identified only to genus level as Campylobacter species. In another 3 isolates, molecular identification was not consistent with the phenotypic identification (C fetus identified as C jejuni).Complications appeared in 23.9% of patients. Quinolone resistance was observed in 50% of the isolates. Only 37.8% of patients received appropriate empirical therapy. Mortality was 16.4%, although it was higher in HIV-infected patients than uninfected patients (33% vs. 10%; p = 0.04), in cases of hospital-acquired Campylobacter bacteremia compared with community-acquired cases (38.5% vs. 9.4%; p = 0.02), and in the presence of complications compared with patients without complications (100% vs. 0%; p < 0.001). The incidence of recurrence was 5% (3 patients with humoral immunodeficiency). There was a higher proportion of HIV-infected patients among patients with Campylobacter bacteremia in the pre-HAART era (1985-1996) than in the HAART era (1997-2007)-27.5% (11/40) vs. 14.3% (4/28)-although the difference was not statistically significant. Debilitating diseases such as chronic obstructive pulmonary disease emerged as predisposing conditions in the HAART era (0% before HAART era vs. 14.3% in HAART era; p = 0.032).Campylobacter bacteremia is no longer a significant disease of HIV-positive patients on HAART, but often affects other immunocompromised patients as well. Campylobacter bacteremia has an extraintestinal origin in as many as 31% of cases, and humoral immunodeficiency must be sought in patients with recurrent episodes. Quinolones should not be considered for empirical therapy.

Clinical outcome of empiric antimicrobial therapy of bacteremia due to extended-spectrum beta-lactamase producing Escherichia coli and Klebsiella pneumoniae

BackgroundPrompt administration of adequate empiric antimicrobial therapy is a major determinant influencing the outcome of serious infections. The objective of this study was to describe empiric antimicrobial therapy employed and assess its effect on the outcome of patients bacteremic with extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae.FindingsA retrospective surveillance study of all patients with bacteremias caused by ESBL-producing E. coli and K. pneumoniae (EK-ESBL) from 2000-2007 in the Calgary Health Region was conducted. Data were available for 79 episodes of bacteremia among 76 patients. Forty-four (56%) were male, the median age was 70.0 yrs [interquartile range (IQR) 60.6-70.1 yrs], and 72 (91%) episodes were E. coli. Seventy-four episodes (94%) were treated with empiric therapy within the first 48 hours. A non-statistically significant increased mortality occurred in those treated empirically with a beta-lactam/beta-lactamase inhibitor combination (6/16; 38% vs. 10/53; 18%; p = 0.063) while empiric carbapenem therapy was associated with lower mortality (0/10 died vs. 16/53 (30%), p = 0.089). Only 42 (53%) episodes received adequate therapy within the first 48 hours. The median time to first adequate antibiotic therapy was 41.0 hours [IQR 5.8-59.5] (n = 75). The case-fatality rate was not different among those that received adequate compared to inadequate therapy by 48 hours as compared to inadequate empiric therapy (9/42; 21% vs. 7/37; 19%; p = 1.0).ConclusionInadequate empiric therapy is common among patients with EK-ESBL bacteremia in our region but was not associated with adverse mortality outcome.