Inadequate Initial Antimicrobial Treatment Research Articles

Trauma and Antimicrobial Resistance Are Independent Predictors of Inadequate Empirical Antimicrobial Treatment of Ventilator-Associated Pneumonia in Critically Ill Patients.

Background: We aimed to assess independent risk factors for inadequate initial antimicrobial treatment (IAT) in critically ill patients with ventilator-associated pneumonia (VAP) treated in intensive care units (ICU) and to determine whether IAT is associated with adverse outcomes in patients with VAP. Patients and Methods: A prospective cohort study was performed and included 152 patients with VAP treated in an ICU for more than 48 hours. The main outcomes of interest were all-cause ICU mortality and VAP-related mortality. Other outcomes considered were: intra-hospital mortality, VAP-related sepsis, relapse, re-infection, length of stay in ICU (ICU LOS), and number of days on mechanical ventilation (MV). Results: One-third of patients (35.5%) received inadequate antimicrobial therapy. Trauma (odds ratio [OR], 3.55; 95% confidence interval [CI], 1.25-10.06) and extensively drug-resistant (XDR) causative agent (OR, 3.09; 95% CI, 1.23-7.74) were independently associated with inadequate IAT. Inadequate IAT was associated with a higher mortality rate (OR, 3.08; 95% CI, 1.30-7.26), VAP-related sepsis (OR, 2.39; 95% CI, 1.07-5.32), relapse (OR, 3.25; 95% CI, 1.34-7.89), re-infection (OR, 6.06; 95% CI, 2.48-14.77), and ICU LOS (β 4.65; 95% CI, 0.93-8.36). Acinetobacter spp., Pseudomonas aeruginosa and Klebsiella/Enterobacter spp. were the most common bacteria in patients with IAT and those with adequate antimicrobial therapy. Conclusions: This study demonstrated that inadequate IAT is associated with a higher risk of the majority of adverse outcomes in patients with VAP treated in ICUs. Trauma and XDR strains of bacteria are independent predictors of inadequate IAT of VAP in critically ill patients.

The clinical impact of Stenotrophomonas maltophilia bacteremia on the 30-day mortality rate in patients with hematologic disorders: a single-institution experience.

Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen, particularly in immunocompromised patients due to their adverse antimicrobial susceptibility pattern. The objective of this article was to investigate the clinical impact of SM bacteremia on the 30-day mortality rate and identify the risk factors of the cause of mortality in patients with hematologic disorders. We retrospectively reviewed the clinical data in patients diagnosed with hematological disorders and SM bacteremia over an 8-year period from July 2010 to July 2018 at a 248-bed hematology department. We compared patients' clinical characteristics and outcomes between the non-survivor and survivor groups. The overall incidence of SM bacteremia was 25.1 per 10,000 admissions. There were 59 patients (median age: 35 years; 57.6% males) included in the study with an overall SM bacteremia-related 30-day mortality of 44.1%. Multi-drug resistance was common. In vitro susceptibility is higher to ceftazidime (72.9%), ciprofloxacin (66.1%) and cefoperazone/sulbactam (59.3%). The risk factors identified in the univariate analysis were catheter re-implantation, accompanying polymicrobial infection, inadequate initial antimicrobial treatment, APACHE II score, temperature > 39°C, septic shock, respiratory failure, and non-remission post treatment for primary diseases. Multivariate analysis further confirmed that inadequate initial antimicrobial treatment, respiratory failure, and non-remission after treatment for hematological diseases are independent risk factors associated with mortality (P=0.001, 0.002 and 0.007, respectively). Our study suggests that SM bacteremia is highly associated with increased mortality in patients with hematologic diseases. Early detection, prompt comprehensive management including initiation of combined sensitive antibiotics, respiratory monitoring and support, platelet infusion, and strategies to improve patients' remission status are recommended to improve the overall survival in patients with SM bacteremia.

Antimicrobial treatment practices among Ugandan children with suspicion of central nervous system infection.

Acute central nervous system (CNS) infections in children in sub-Saharan Africa are often fatal. Potential contributors include late presentation, limited diagnostic capacity and inadequate treatment. A more nuanced understanding of treatment practices with a goal of optimizing such practices is critical to prevent avoidable case fatality. We describe empiric antimicrobial treatment, antibiotic resistance and treatment adequacy in a prospective cohort of 459 children aged two months to 12 years hospitalised for suspected acute CNS infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155 had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%), 58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219 children with laboratory-confirmed malaria and/or bacterial infections, 182 (83.1%) received an adequate antimalarial and/or antibiotic on the day of admission and 211 (96.3%) within 48 hours of admission. The proportion of those receiving adequate treatment was similar among survivors and non-survivors. All bacterial isolates were sensitive to ceftriaxone except one Escherichia coli isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality was not a result of inadequate initial antimicrobial treatment at the hospital. The epidemiology of CNS infection in this setting justifies empirical use of a third-generation cephalosporin, however antibiotic resistance should be monitored closely.

Predictors of mortality in bloodstream infections caused by multidrug-resistant gram-negative bacteria: 4 years of collection.

The study was undertaken to describe the profile of patients and the characteristics of all multidrug-resistant gram-negative bacteria (MDR-GNB) and to assess mortality. We examined 138 patients with bloodstream infections (BSIs) caused by MDR-GNB. Clinical characteristics, antibiotic therapy, and in-hospital mortality were analyzed. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. The in-hospital mortality rate was 25.4%. Univariate analysis revealed that comorbidities and inadequate initial antimicrobial treatment could increase risk of death. In Cox regression analysis, mortality was independently associated with the age (P = .034), hospitalization in an intensive care unit (ICU) (P = .04), invasive procedures (P < .001), and Acute Physiology and Chronic Health Evaluation II scores (P < .001), whereas combination therapy or monotherapy was not associated with mortality (P = .829). Postantibiogram therapy was associated with hospitalization in an ICU (P = .006), Charlson comorbidity index score (P = .003), and inadequate initial antimicrobial treatment (P < .001). MDR-GNB strains and antimicrobial regimens were not the major risk factors of mortality. Inadequate initial antimicrobial treatment, invasive procedures, high Acute Physiology And Chronic Health Evaluation II scores, hospitalization in an ICU, and comorbidities were the important factors responsible for mortality. Although there was no difference between combination therapy and monotherapy in mortality, combined treatment may be more effective than monotherapy for patients in an ICU, with a Charlson comorbidity index score < 4, or inadequate initial antimicrobial treatment.

The Effect of Inadequate Initial Empiric Antimicrobial Treatment on Mortality in Critically Ill Patients with Bloodstream Infections: A Multi-Centre Retrospective Cohort Study.

Hospital mortality rates are elevated in critically ill patients with bloodstream infections. Given that mortality may be even higher if appropriate treatment is delayed, we sought to determine the effect of inadequate initial empiric treatment on mortality in these patients. A retrospective cohort study was conducted across 13 intensive care units in Canada. We defined inadequate initial empiric treatment as not receiving at least one dose of an antimicrobial to which the causative pathogen(s) was susceptible within one day of initial blood culture. We evaluated the association between inadequate initial treatment and hospital mortality using a random effects multivariable logistic regression model. Among 1,190 patients (1,097 had bacteremia and 93 had candidemia), 476 (40%) died and 266 (22%) received inadequate initial treatment. Candidemic patients more often had inadequate initial empiric therapy (64.5% versus 18.8%), as well as longer delays to final culture results (4 vs 3 days) and appropriate therapy (2 vs 0 days). After adjustment, there was no detectable association between inadequate initial treatment and mortality among bacteremic patients (Odds Ratio (OR): 1.02, 95% Confidence Interval (CI) 0.70–1.48); however, candidemic patients receiving inadequate treatment had nearly three times the odds of death (OR: 2.89, 95% CI: 1.05–7.99). Inadequate initial empiric antimicrobial treatment was not associated with increased mortality in bacteremic patients, but was an important risk factor in the subgroup of candidemic patients. Further research is warranted to improve early diagnostic and risk prediction methods in candidemic patients.

The Effect of Inadequate Initial Antimicrobial Treatment on Mortality in Critically Ill Patients With Bloodstream Infections

The Effect of Inadequate Initial Antimicrobial Treatment on Mortality in Critically Ill Patients With Bloodstream Infections

Double Trouble: Influenza and S aureus Co-infection

Nguyen T, Kyle UG, Jaimon N, et al. Co-infection with Staphylococcus aureus increases risk of severe coagulopathy in critically ill children with influenza A (H1N1) virus infection. Crit Care Med. 2012; 40(12): 3246– 3250; doi: 10.1097/CCM.0b013e318260c7f8Investigators from Baylor College of Medicine conducted an observational study of pediatric patients admitted to the PICU from 2009 to 2010 with either confirmed or suspected influenza infection to assess the effect of bacterial co-infection on morbidity and mortality. Confirmed influenza infection was defined as any positive laboratory test for influenza A or B virus infection. Confirmed cases were further subtyped using PCR for H1N1, but this was incomplete since the study began prior to the introduction of PCR primers specific for H1N1. A clinically relevant bacterial co-infection was defined as: (1) empiric treatment of a clinical diagnosis of bacterial pneumonia, (2) bacterial super-infection within 72 hours of the initial PICU admission from a sterile site (respiratory secretions or blood), or (3) a bacterial pathogen identified in the patient’s respiratory secretions. Comorbidities and treatment with regular- and high-dose oseltamivir were recorded. The following outcomes were compared between patients with and without methicillin-sensitive or -resistant S aureus (MSSA/MRSA) co-infection: severity of illness within the first 24 hours of admission using the Pediatric Risk of Mortality III acute physiology (PRISM) score,1 receipt of vasoactive medications, duration of PICU care, survival at day 90, and disseminated intravascular coagulation (DIC).Of the 66 children enrolled, 59% were males and the mean age was 5.9 years. A total of 64% had H1N1 and 36% were influenza A-positive but not subtyped. Bacterial co-infections were present in 52% of patients, with 35% of these being MSSA/MRSA. Fifty-five percent of patients had comorbidities, most commonly asthma (14%), chronic lung disease (11%), and developmental delay (14%). Fifty-nine percent of patients were treated with high-dose oseltamivir and 20% with regular-dose oseltamivir.Compared to those without co-infection, children with MSSA/ MRSA had a significantly greater severity of illness (median PRISM III score 14 vs 6), receipt of vasoactive medications (58% vs 22%), and duration of PICU care (median 11.0 vs 5.5 days). Survival at day 90 was not significantly different between those with MSSA/MRSA co-infection and no co-infection (83% vs 91%). Patients with MSSA/ MRSA co-infection were significantly more likely to have DIC than those without co-infection.The authors conclude that among children admitted to the PICU with influenza A or H1N1, those with a higher level of severity of illness are at increased risk of MSSA/MRSA and DIC.H1N1 influenza emerged as a novel strain of the influenza virus during 2009 and 2010 leading to a global pandemic. Unlike most influenza A strains, H1N1 has a predilection to cause disease in children and young adults, and young age was a risk factor for H1N1-associated deaths.2 The Centers for Disease Control and Prevention (CDC) identified 338 influenza-associated pediatric deaths during the outbreak, a fourfold increase in annual influenza-related deaths. Ninety-two percent of fatal cases were attributed to H1N1.3 Among fatal cases, co-infection with bacteria was approximately twice as common in children compared to adults.4 Secondary infections complicating influenza infection include bloodstream infections (BSI) due to S pneumoniae, S pyogenes and S aureus. BSI increased during the H1N1 epidemic, with the greatest increase for pneumococcal bacteremia among children <5 years old.5Several mechanisms are proposed for this viral-bacterial virulence, including viral-induced airway changes favoring bacterial growth and viral-induced defects in immune responses.5 The current study suggests another pathological process for increased virulence associated with MSSA/MRSA: increased risk of DIC. DIC and inadequate initial antimicrobial treatment are both associated with increased risk of death.6Approximately 15% of hospitalized pediatric H1N1 patients required intensive care.7 A previous multicenter US report of children with H1N1 treated in an ICU found that 70% had 1 or more chronic conditions. The majority developed respiratory failure treated with mechanical ventilation (67%) and 19% received vasoactive medications. Mortality was 9%, and among previously well children, MRSA co-infection was associated with an eightfold increased risk of death.8Both primary and hospital-based care providers can improve pediatric health by strictly adhering to influenza vaccination recommendations. All children ≥6 months old should be vaccinated against influenza every year. As this study reminds us, influenza causes significant mortality and morbidity in children and the best treatment is prevention.

Clinical consequences of increased ciprofloxacin and gentamicin resistance in patients with Escherichia coli bacteraemia in the Netherlands

Escherichia coli is a common cause of bacteraemia and is increasingly resistant to ciprofloxacin and gentamicin. The primary objective of this study was to investigate how often this leads to inadequate initial antimicrobial treatment. Secondary goals were to determine factors associated with inadequate empirical therapy and to assess its impact on mortality and length of stay. All patients with an E. coli bacteraemia hospitalized in 2008 were identified retrospectively. Initial antimicrobial therapy and clinical outcomes of all patients with an isolate resistant to gentamicin and/or ciprofloxacin (cases) were compared to those of a group of randomly selected patients in whom a gentamicin and ciprofloxacin susceptible E. coli was isolated (controls). One hundred and thirty-six unique patients had E. coli bacteraemia. Of these, 34 patients were identified as cases and were compared to 34 controls. Among the cases, 97% of the E. coli was resistant to ciprofloxacin and 44% to gentamicin. Resistance to amoxicillin was high in both cases (94%) and controls (65%). In 41% of the cases initial antimicrobial therapy was inadequate, compared to only 3% in the controls. The majority of inadequately treated cases had a biliary focus (64%). Infections in cases were more often healthcare-associated than infections in controls (62% vs 26%). E. coli with the same resistance pattern had been isolated before in adequately treated cases more often than in inadequately treated cases. Mortality did not differ significantly between cases and controls. Neither ciprofloxacin nor amoxicillin should be used as empirical therapy in patients with a presumed E. coli bacteraemia.

Pharmacoeconomic analysis of bacteraemia caused by gram negative Extended Spectrum Beta Lactamase (ESBL) producers: Category: Scientific free paper

Tumbarello et al (Predictors of Mortality in Patients with Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae: Importance of Inadequate Initial Antimicrobial Treatment, AAC June 2007) showed higher mortality with ESBL bacteraemia where treatment is initiated with inappropriate antibiotics (60% vs. 20% approximately). Dellinger, Levy and Carlet et al state that severe sepsis causes mortality between 28-50% (Surviving Sepsis Campaign, Crit Care Med 2008). Our bacteraemia surveillance shows that ESBL producers are becoming more prevalent.

Costs of Bloodstream Infections Caused by Escherichia coli and Influence of Extended-Spectrum-β-Lactamase Production and Inadequate Initial Antibiotic Therapy

Escherichia coli is the leading cause of bloodstream infections (BSIs) caused by Gram-negative bacteria. The increasing prevalence of antibiotic-resistant E. coli strains, particularly those producing extended-spectrum β-lactamases (ESBLs), increases the odds that empirically prescribed antimicrobial therapy for these infections will be inadequate, but the economic impact of this risk has not been fully evaluated. In the present retrospective 1-year analysis of 134 consecutive E. coli BSIs in our hospital, we explored the clinical and economic impacts of (i) inadequate initial antimicrobial treatment (IIAT) (i.e., empirical treatment with drugs to which the isolate had displayed in vitro resistance) of these infections and (ii) ESBL production by the bloodstream isolate. Cost data were obtained from the hospital accounting system. Compared with the 107 (79.8%) adequately treated patients, the 27 (20.1%) who received IIAT had a higher proportion of ESBL BSIs (74.0% versus 15.8%), longer (+6 days) and more costly (+EUR 4,322.00) post-BSI-onset hospital stays, and higher 21-day mortality rates (40.7% versus 5.6%). Compared with the 97 non-ESBL infections, the 37 (27.6%) ESBL BSIs were also associated with longer (+7 days) and more costly (+EUR 5,026.00) post-BSI-onset hospital stays and increased 21-day mortality (29.7% versus 6.1%). These findings confirm that the hospital costs and mortality associated with E. coli BSIs are significantly increased by ESBL production and by IIAT.

Cost and mortality prediction using polymerase chain reaction pathogen detection in sepsis: evidence from three observational trials

IntroductionDelays in adequate antimicrobial treatment contribute to high cost and mortality in sepsis. Polymerase chain reaction (PCR) assays are used alongside conventional cultures to accelerate the identification of microorganisms. We analyze the impact on medical outcomes and healthcare costs if improved adequacy of antimicrobial therapy is achieved by providing immediate coverage after positive PCR reports.MethodsA mathematical prediction model describes the impact of PCR-based rapid adjustment of antimicrobial treatment. The model is applied to predict cost and medical outcomes for 221 sepsis episodes of 189 post-surgical and intensive care unit (ICU) sepsis patients with available PCR data from a prospective, observational trial of a multiplex PCR assay in five hospitals. While this trial demonstrated reduction of inadequate treatment days, data on outcomes associated with reduced inadequate initial antimicrobial treatment had to be obtained from two other, bigger, studies which involved 1,147 (thereof 316 inadequately treated) medical or surgical ICU patients. Our results are reported with the (5% to 95%) percentile ranges from Monte Carlo simulation in which the input parameters were randomly and independently varied according to their statistical characterization in the three underlying studies. The model allows predictions also for different patient groups or PCR assays.ResultsA total of 13.1% of PCR tests enabled earlier adequate treatment. We predict that cost for PCR testing (300 €/test) can be fully recovered for patients above 717 € (605 € to 1,710 €) daily treatment cost. A 2.6% (2.0 to 3.2%) absolute reduction of mortality is expected. Cost per incremental survivor calculates to 11,477 € (9,321 € to 14,977 €) and incremental cost-effectiveness ratio to 3,107 € (2,523 € to 4,055 €) per quality-adjusted life-year. Generally, for ICU patients with >25% incidence of inadequate empiric antimicrobial treatment, and at least 15% with a positive blood culture, PCR represents a cost-neutral adjunct method.ConclusionsRapid PCR identification of microorganisms has the potential to become a cost-effective component for managing sepsis. The prediction model tested with data from three observational trials should be utilized as a framework to deepen insights when integrating more complementary data associated with utilization of molecular assays in the management of sepsis.

The Use of Carbapenems in the Treatment of Serious Infections

Inadequate initial antimicrobial treatment in serious infections leads to increased mortality. Achieving adequate treatment is increasingly difficult because of the increasing prevalence of multidrug-resistant (MDR) pathogens. The carbapenems are potent, broad-spectrum antibiotics that have been shown to be safe and efficacious therapies in the treatment of serious infections. This review is intended to compare the 4 major members of the carbapenem class, which include imipenem, meropenem, ertapenem, and doripenem, with other widely used antimicrobial agents in the intensive care unit (ICU). The carbapenems are potent, broad-spectrum antibiotics that have been shown to be safe and efficacious therapies in the treatment of serious infections. They provide better gram-negative coverage than other beta-lactams and are stable against extended-spectrum beta-lactamases and AmpC beta-lactamases, making them effective in the treatment of many MDR bacteria. The newly approved carbapenem, doripenem, may help preserve the utility of the carbapenem class.

Management of patients with community-acquired pneumonia in a primary care hospital: a critical evaluation

The aim of the study was to evaluate routine management of patients with community-acquired pneumonia (CAP) with regard to severity patterns, diagnostic approaches and results, as well as initial empiric antimicrobial treatment and its impact on outcome.Two hundred and thirty-two consecutive patients with CAP admitted to a primary care hospital were studied prospectively. Patients were classified according to Fine's severity score. Severe pneumonia was defined as admission at the ICU. Diagnostic approaches and initial antimicrobial treatment were judged according to the guidelines of the European Respiratory Society (ERS).Fifty-five patients (24%) had mild, 156 (67%) moderate, and 21 (9%) severe CAP. At least one microbial examination was performed in 124 patients (54%). There was no association between microbial investigation and severity of CAP. Inadequate initial antimicrobial treatment was significantly more frequent in severe (18/21, 86%), than in mild (5/55, 9%) and moderate CAP (39/156, 25%, P< 0·0001). Conversely, antimicrobial overtreatment occurred significantly more often in mild (30/55, 55%) and moderate (77/156, 49%) than in severe CAP (0/21, 0%, P<0·0001). Inadequate initial antimicrobial treatment was more frequent in non-responders [18/62 (29%) vs. 31/170, (18%), RR 1·6 95% CI 0·9–2·6, P=0·07] and was associated with a longer duration of hospitalization (17±11 vs. 14±8 days, P=0·03). Mortality was not affected by inadequate initial antimicrobial treatment [5/62 (8%) vs. 10/170 (6%), RR 1·4 95% CI 0·5–3·9, P=0·55].Principal conceptual weaknesses which might be subject to intervention were (1) the hospitalization of patients with mild pneumonia at low risk of mortality; (2) the lack of association between microbial investigation and severity of CAP; (3) antimicrobial overtreatment of patients with non-severe CAP; and (4) inadequate antimicrobial treatment with increased number of primary treatment failures and duration of hospitalization.