Inadequate Initial Antibiotic Therapy Research Articles

Antibiotic Susceptibility Patterns among Indonesian Adults Hospitalized with Pneumonia

Introduction: Pneumonia continues to be a global issue with significant morbidity and mortality rates. Increased multidrug-resistant (MDR) bacterial pneumonia, aging populations, chronically ill patients, and inadequate initial antibiotic therapy increase hospitalized pneumonia patients' morbidity and mortality. This study aimed to analyze the microbiological pattern and choose a therapy based on local antibiotic susceptibility patterns. Methods: From January 2020 to December 2022, a retrospective cross-sectional study was conducted on hospitalized pneumonia patients at Haji General Hospital, Surabaya, Indonesia. Data from medical records were gathered to illustrate patient features, bacterial culture, and antimicrobial susceptibility tests. This study included 172 patients. In this study, no specific statistical analysis was performed. The data were reported as a percentage (%). Results: The patients were mostly 56-65 years old (36.6%) and male (55.2%). The most common comorbidities were cardiovascular disease (17.3%), and the others were diabetes mellitus (14.0%), cerebral vascular attack (CVA) (10.7%), and coronavirus infection (8.9%). Based on the sputum culture, the bacteria identified were Klebsiella pneumoniae (25.0%), Pseudomonas aeruginosa (20.9%), Acinetobacter baumannii (15.7%), and Escherichia coli (11.6%). The most common bacteria isolated from sputum cultures was Klebsiella pneumoniae, which was more susceptible to amikacin and meropenem. Conclusion: Only amikacin was an antibiotic susceptible to four primary pathogens. Rates of resistance to ciprofloxacin and ceftriaxone were high, and these empiric antibiotics should be used with caution in these patients.

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006–May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

Impacts of Multidrug-Resistant Pathogens and Inappropriate Initial Antibiotic Therapy on the Outcomes of Neonates with Ventilator-Associated Pneumonia.

: BackgroundIt is unknown whether neonatal ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) pathogens and inappropriate initial antibiotic treatment is associated with poor outcomes after adjusting for confounders. Methods: We prospectively observed all neonates with a definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and March 2020. All clinical features, therapeutic interventions, and outcomes were compared between the MDR–VAP and non-MDR–VAP groups. Multivariate regression analyses were used to investigate independent risk factors for treatment failure. Results: Of 720 neonates who were intubated for more than 2 days, 184 had a total of 245 VAP episodes. The incidence rate of neonatal VAP was 10.1 episodes/per 1000 ventilator days. Ninety-six cases (39.2%) were caused by MDR pathogens. Neonates with MDR–VAP were more likely to receive inadequate initial antibiotic therapy (51.0% versus 4.7%; p < 0.001) and had delayed resolution of clinical symptoms (38.5% versus 25.5%; p = 0.034), although final treatment outcomes were comparable with the non-MDR–VAP group. Inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. The VAP-attributable mortality rate and overall mortality rate of this cohort were 3.7% and 12.0%, respectively. Independent risk factors for treatment failure included presence of concurrent bacteremia (OR 4.83; 95% CI 2.03–11.51; p < 0.001), septic shock (OR 3.06; 95% CI 1.07–8.72; p = 0.037), neonates on high-frequency oscillatory ventilator (OR 4.10; 95% CI 1.70–9.88; p = 0.002), and underlying neurological sequelae (OR 3.35; 95% CI 1.47–7.67; p = 0.004). Conclusions: MDR–VAP accounted for 39.2% of all neonatal VAP in the neonatal intensive care unit (NICU), but neither inappropriate initial antibiotics nor MDR pathogens were associated with treatment failure. Neonatal VAP with concurrent bacteremia, septic shock, and underlying neurological sequelae were independently associated with final worse outcomes.

Drug Prevention and Control of Ventilator-Associated Pneumonia.

Ventilator-associated pneumonia (VAP) is one of the most prevalent and serious complications of mechanical ventilation, which is considered a common nosocomial infection in critically ill patients. There are some great options for the prevention of VAP: (i) minimize ventilator exposure; (ii) intensive oral care; (iii) aspiration of subglottic secretions; (iv) maintain optimal positioning and encourage mobility; and (v) prophylactic probiotics. Furthermore, clinical management of VAP depends on appropriate antimicrobial therapy, which needs to be selected based on individual patient factors, such as previous antibacterial therapy, history of hospitalization or mechanical ventilation, and bacterial pathogens and antibiotic resistance patterns. In fact, antibiotic resistance has exponentially increased over the last decade, and the isolation of a multidrug-resistant (MDR) pathogen has been identified as an independent predictor of inadequate initial antibiotic therapy and which is significantly associated with increased mortality. Multiple attempts were used in the treatment of VAP, such as novel antibacterial agents, inhaled antibiotics and monoclonal antibodies. In this review, we summarize the current therapeutic options for the prevention and treatment of VAP, aiming to better management of VAP in clinical practice.

Infections related to healthcare in patients hospitalized in a Urology service: Resistance patterns and adequacy of empirical antibiotic treatment as a prognostic factor

ObjectivesTo evaluate the suitability of empirical antibiotic therapy in HAIs and the antibiotic resistance patterns of the responsible microorganisms, as well as the incidence of mortality and risk factors involved. MethodA prospective observational study was carried out on patients of both sexes older than 16years, admitted by any urological process during a period of 4years. The incidence and characteristics of HAIs, as well as the causative organism and its resistance, the initial empirical antibiotic therapy and its modification, if required, and mortality rates are analyzed. ResultsOut of 6546 patients, 6.3% suffered HAIs, 70.5% corresponding to urinary tract infection and 22.1% to infection of the surgical wound. E.coli, Enterococcus spp., Klebsiella spp. y P.aeruginosa were the most frequently implicated (25.1%, 17.5%, 13.5% and 12.3%, respectively). E.coli and Klebsiella spp. were producers of extended-spectrum beta-lactamases (ESBL) in 24.7% and 47.8%, respectively. 4.3% of Klebsiella and 33.3% of Pseudomonas were carbapenems-resistant. The overall resistance to quinolones was approximately 50%. The most commonly used antibiotics for empirical therapy were cephalosporins of 3rd and 4th generation (33.6%) and carbapenems (28.2%). An overall rate of adequacy of empirical antibiotic therapy of 82.9% was obtained. The mortality rate in patients with HAIs was 2.2%, compared with 0.3% in patients without infection. In a multivariate analysis, the variables associated with the highest mortality risk were the isolation of ESBL-producing enterobacteria and the inadequate empirical antibiotic treatment. ConclusionsThe selection of empirical antibiotic therapy was quite accurate. An increase in HAIs by multiresistant microorganisms, such as ESBL Enterobacteria or multiresistant P.aeruginosa is being observed. The mortality risk increases with inadequate initial empirical antibiotic therapy or when the responsible microorganism is an ESBL enterobacteria.

Infecciones relacionadas con la asistencia sanitaria en pacientes ingresados en un servicio de Urología: patrones de resistencia y adecuación del tratamiento antibiótico empírico como factor pronóstico

ObjectivesTo evaluate the suitability of empirical antibiotic therapy in HAIs and the antibiotic resistance patterns of the responsible microorganisms, as well as the incidence of mortality and risk factors involved. MethodA prospective observational study was carried out on patients of both sexes older than 16years, admitted by any urological process during a period of 4years. The incidence and characteristics of HAIs, as well as the causative organism and its resistance, the initial empirical antibiotic therapy and its modification, if required, and mortality rates are analysed. ResultsOut of 6,546 patients, 6.3% suffered HAIs, 70.5% corresponding to urinary tract infection and 22.1% to infection of the surgical wound. E.coli, Enterococcus spp., Klebsiella spp. y P.aeruginosa were the most frequently implicated (25.1%, 17.5%, 13.5% and 12.3%, respectively). E.coli and Klebsiella spp. were producers of extended-spectrum beta-lactamases (ESBL) in 24.7% and 47.8%, respectively. 4.3% of Klebsiella and 33.3% of Pseudomonas were carbapenems-resistant. The overall resistance to quinolones was approximately 50%. The most commonly used antibiotics for empirical therapy were cephalosporins of 3rd and 4th generation (33.6%) and carbapenems (28.2%). An overall rate of adequacy of empirical antibiotic therapy of 82.9% was obtained. The mortality rate in patients with HAIs was 2.2%, compared with 0.3% in patients without infection. In a multivariate analysis, the variables associated with the highest mortality risk were the isolation of ESBL-producing enterobacteria and the inadequate empirical antibiotic treatment. ConclusionsThe selection of empirical antibiotic therapy was quite accurate. An increase in HAIs by multiresistant microorganisms, such as ESBL Enterobacteria or multiresistant P.aeruginosa is being observed. The mortality risk increases with inadequate initial empirical antibiotic therapy or when the responsible microorganism is an ESBL enterobacteria.

Evaluating vancomycin and piperacillin-tazobactam in ED patients with severe sepsis and septic shock

Study objectiveTo determine the frequency and cause of inadequate initial antibiotic therapy with vancomycin and piperacillin-tazobactam in patients with severe sepsis and septic shock in the emergency department (ED), characterize its impact on patient outcomes, and identify patients who would benefit from an alternative initial empiric regimen. MethodsRetrospective cohort study conducted between 2012 and 2015 in which 342 patients with culture-positive severe sepsis or septic shock who received initial vancomycin and piperacillin-tazobactam were reviewed to determine appropriateness of antimicrobial therapy, risk factors for inappropriate use, and outcome data. Univariate and multivariate regression analyses were determined to identify associations between inappropriate antibiotic use and outcomes and to identify risk factors that may predict which patients would benefit from an alternative initial regimen. ResultsVancomycin and piperacillin-tazobactam were inappropriate for 24% of patients with severe sepsis or septic shock, largely due to non-susceptible infections, particularly ESBL organisms and Clostridium difficile. Risk factors included multiple sources of infection (OR 4.383), admission from a skilled nursing facility (OR 3.763), a history of chronic obstructive pulmonary disease (COPD) (OR 3.175), intra-abdominal infection (OR 2.890), and immunosuppression (OR 1.930). We did not find a mortality impact. ConclusionVancomycin and piperacillin-tazobactam were an inappropriate antibiotic combination for approximately 24% of patients with either severe sepsis or septic shock in the ED. Patients with known COPD, residence at a skilled nursing facility, a history concerning for Clostridium difficile, and immunosuppression would benefit from an alternative regimen. Future prospective studies are needed to validate these findings.

Impact of combination therapy and early de-escalation on outcome of ventilator-associated pneumonia caused by Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Guidelines recommend dual coverage of P. aeruginosa, but the beneficial effect of combination therapy is controversial. We described antibiotic prescriptions and evaluated the clinical impact of initial combination antibiotic therapy and de-escalation strategy in patients with VAP caused by P. aeruginosa.Methods: Between 1994 and 2014, all 100 patients with VAP caused by P. aeruginosa in our intensive care unit (ICU) were included in a retrospective cohort study to evaluate the prognostic impact of initial combination antibiotic therapy.Results: Eighty-five patients received initial combination antibiotic therapy and 15 monotherapy. Nine patients received inadequate initial antibiotic therapy. De-escalation was performed in 42 patients. Thirty-nine patients died in the ICU. Factors independently associated with death were SAPS II score [SAPS II ≥40 versus <40: hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.08–5.70, p = 0.03] and septic shock (HR = 4.80, 95% CI = 1.90–12.16, p < 0.01) at onset of VAP. Initial combination antibiotic therapy (HR = 1.97, 95% CI = 0.56–6.93, p = 0.29) and early de-escalation (HR = 0.59, 95% CI = 0.27–1.31, p = 0.19) had no impact on mortality. In multivariate analysis, the risk for inappropriate initial antibiotic therapy was higher in cases with multi-drug resistant P. aeruginosa [odd ratio (OR) = 7.11, 95% CI = 1.42–35.51, p = 0.02], but lower in cases with initial combination antibiotic therapy (OR = 0.12, 95% CI = 0.02–0.63, p = 0.01).Conclusion: In our cohort, combination therapy increased the likelihood of appropriate therapy but did not seem to impact on mortality.

Predominance of healthcare-associated cases among episodes of community-onset bacteraemia due to extended-spectrum β-lactamase-producing Enterobacteriaceae

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) are endemic pathogens worldwide. Infection with ESBL-PE may be associated with inadequate antibiotic therapy and a poor outcome. However, risk factors for ESBL-PE community-acquired infections are ill-defined. An observational multicentre study was performed in 50 hospitals to identify the prevalence of and risk factors for community-acquired ESBL-PE bacteraemia. All patients presenting with community-onset Enterobacteriaceae bacteraemia were recorded over a 2-month period (between June and November 2013). Risk factors and 14-day outcomes of patients were investigated. Among 682 Enterobacteriaceae bacteraemia episodes recorded, 58 (8.5%) were caused by ESBL-PE. The most frequent species isolated were Escherichia coli (537; 76.7%) and Klebsiella spp. (68; 9.7%), of which 49 (9.1%) and 8 (11.8%), respectively, were ESBL-producers. Most ESBL-PE episodes were healthcare-associated, and only 22 (38%) were apparently community-acquired. The main risk factor for community-acquired ESBL-PE bacteraemia was a prior hospital stay of ≥5 days within the past year. The overall 14-day survival was 90%; only 4 (6.9%) of 58 patients with ESBL-PE bacteraemia died. Inadequate initial antibiotic therapy was administered to 55% of patients with ESBL-PE bacteraemia but was not associated with increased 14-day mortality. Although many patients had community-onset ESBL-PE bacteraemia, almost two-thirds of the episodes were actually healthcare-associated, and true community-acquired ESBL-PE bacteraemia remains rare. In our essentially non-severely ill population, inappropriate initial therapy was not associated with a higher risk of mortality.

Empirical Combination Antibiotic Therapy Improves the Outcome of Nosocomial Meningitis or Ventriculitis in Neuro-Critical Care Unit Patients

Nosocomial meningitis and ventriculitis (MEN) are serious complications in neuro-critical care unit (NCCU) patients. Few data are available on the risk factors and mortality rates among NCCU patients with these disorders caused by multi-drug-resistant (MDR) pathogens. Our aim was to identify the risk factors for MEN caused by such pathogens and in-hospital deaths in critically ill neurologic patients and to evaluate the impact of empirical combination antibiotic therapy (ECAT) on the outcomes of these patients. We conducted a retrospective study of critically ill neurologic patients having nosocomial MEN who were admitted to the NCCU in a university teaching hospital from January 2003 to December 2013, with MEN being defined using the modified U.S. Centers for Disease Control and Prevention criteria for nosocomial infections. In total, 6,149 consecutive NCCU patients were screened; 132 had MEN. Logistic regression analysis demonstrated that MDR MEN was related to infection with gram-negative (GN) bacteria (odds ratio 3.16; 95% confidence interval [CI] 1.08-9.25; p = 0.036), and inadequate initial antibiotic therapy (odds ratio 9.80; 95% CI 3.79-25.32; p < 0.001). The ECAT was associated with a lower mortality rate (hazard ratio 0.35; 95% CI 0.14-0.86; p = 0.022) in Cox proportional hazard regression analysis. The other variable independently associated with a greater mortality rate was a greater Simplified Acute Physiology Score II (hazard ratio 1.07; 95% CI 1.01-1.13; p = 0.018). Initial combination therapy improves the in-hospital mortality rate among NCCU patients with nosocomial MEN. Inadequate initial antibiotic therapy and GN infection were associated with MDR MEN.

Epidemiology and Burden of Bloodstream Infections Caused by Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae in a Pediatric Hospital in Senegal.

ContextSevere bacterial infections are not considered as a leading cause of death in young children in sub-Saharan Africa. The worldwide emergence of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) could change the paradigm, especially in neonates who are at high risk of developing healthcare-associated infections.ObjectiveTo evaluate the epidemiology and the burden of ESBL-E bloodstream infections (BSI).MethodsA case-case-control study was conducted in patients admitted in a pediatric hospital during two consecutive years. Cases were patients with Enterobacteriaceae BSI and included ESBL-positive (cases 1) and ESBL-negative BSI (cases 2). Controls were patients with no BSI. Multivariate analysis using a stepwise logistic regression was performed to identify risk factors for ESBL acquisition and for fatal outcomes. A multistate model was used to estimate the excess length of hospital stay (LOS) attributable to ESBL production while accounting for time of infection. Cox proportional hazards models were performed to assess the independent effect of ESBL-positive and negative BSI on LOS.ResultsThe incidence rate of ESBL-E BSI was of 1.52 cases/1000 patient-days (95% CI: 1.2–5.6 cases per 1000 patient-days). Multivariate analysis showed that independent risk factors for ESBL-BSI acquisition were related to underlying comorbidities (sickle cell disease OR = 3.1 (95%CI: 2.3–4.9), malnutrition OR = 2.0 (95%CI: 1.7–2.6)) and invasive procedures (mechanical ventilation OR = 3.5 (95%CI: 2.7–5.3)). Neonates were also identified to be at risk for ESBL-E BSI. Inadequate initial antibiotic therapy was more frequent in ESBL-positive BSI than ESBL-negative BSI (94.2% versus 5.7%, p<0.0001). ESBL-positive BSI was associated with higher case-fatality rate than ESBL-negative BSI (54.8% versus 15.4%, p<0.001). Multistate modelling indicated an excess LOS attributable to ESBL production of 4.3 days. The adjusted end-of-LOS hazard ratio for ESBL-positive BSI was 0.07 (95%CI, 0.04–0.12).ConclusionControl of ESBL-E spread is an emergency in pediatric populations and could be achieved with simple cost-effective measures such as hand hygiene, proper management of excreta and better stewardship of antibiotic use, especially for empirical therapy.

Infection with multidrug‐resistant gram‐negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes

ObjectiveThis study aimed at evaluating the predictors and outcomes associated with multidrug‐resistant gram‐negative bacterial (MDR‐GNB) infections in an oncology pediatric intensive care unit (PICU). MethodsData were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR‐GNB and (2) infections attributed to non‐MDR‐GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare‐associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7‐ and 30‐day mortality. ResultsMultivariate logistic regression analyses showed significant relationships between MDR‐GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282–21.594; p=0.021) and healthcare‐associated infection (OR 18.360; 95% CI 1.778–189.560; p=0.015). There were significant differences between MDR‐GNB and non‐MDR‐GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. ConclusionsHematologic malignancy and healthcare‐associated infection were significantly associated with MDR‐GNB infection in this sample of pediatric oncology patients.

Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes

ObjectiveThis study aimed at evaluating the predictors and outcomes associated with multidrug-resistant gram-negative bacterial (MDR-GNB) infections in an oncology pediatric intensive care unit (PICU). MethodsData were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR-GNB and (2) infections attributed to non-MDR-GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare-associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7- and 30-day mortality. ResultsMultivariate logistic regression analyses showed significant relationships between MDR-GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282–21.594; p=0.021) and healthcare-associated infection (OR 18.360; 95% CI 1.778–189.560; p=0.015). There were significant differences between MDR-GNB and non-MDR-GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. ConclusionsHematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients.

Risk Factors and Outcomes for Multidrug-Resistant Gram-Negative Bacteremia in the NICU

To assess the risk factors antibiotic therapy and outcomes of multidrug-resistant (MDR) Gram-negative bacilli (GNB) bacteremia in NICU patients. Episodes of MDR GNB bacteremia were compared with a non-MDR GNB bacteremia group in an 8-year cohort study. Of 1106 bacteremias, 393 (35.5%) were caused by GNB. Seventy (18.6%) were caused by an MDR strain. The most frequent mechanism of resistance was extended-spectrum β-lactamase production (67.1%), mainly by Klebsiella pneumoniae (59.6%). Previous antibiotic exposure to third-generation cephalosporin (odds ratio [OR]: 5.97; 95% confidence interval [CI]: 2.37-15.08; P < .001) and carbapenem (OR: 3.60; 95% CI: 1.26-10.29; P = .017) and underlying renal disease (OR: 7.08; 95% CI: 1.74-28.83; P = .006) were identified as independent risk factors for MDR GNB acquisition. Patients with MDR GNB bacteremia more likely received inadequate initial antibiotic therapy (72.9% vs 7.8%; P < .001) had higher rates of infectious complication (21.4% vs 10.5%; P = .011) and overall case fatality +rate (28.6% vs 10.5%; P < .001). Independent risk factors for overall mortality were presence of infectious complications after bacteremia (OR: 3.16; 95% CI: 1.41-7.08; P = .005) and underlying secondary pulmonary hypertension with or without cor pulmonale (OR: 6.19; 95% CI: 1.88-20.31; P = .003). MDR GNB accounted for 18.6% of all neonatal GNB bacteremia in the NICU, especially in those with previous broad-spectrum antibiotic therapy and underlying renal disease. The most frequent mechanism of resistance was extended-spectrum β-lactamase (ESBL) production. Neonates with MDR GNB were more likely to develop infectious complications, which were independently associated with a higher overall case-fatality rate.

Bacteremia Caused by &amp;lt;i&amp;gt;Acinetobacter baumannii&amp;lt;/i&amp;gt;: Epidemiologic Features, Antimicrobial Susceptibility, and Outcomes

Acinetobacter baumannii bacteremia is becoming more prevalent and is associated with increasing morbidity and mortality. Escalating antibacterial resistance further contributes to therapeutic dilemmas, enhanced infection control support and poorer outcomes in patients infected with these bacteria. A retrospective analysis of patients whose blood cultures produced A. baumannii from January 2007 through January 2013 was performed. Data regarding the epidemiologic features, antimicrobial susceptibility and outcomes of patients with A. baumannii bacteremia were collected and analyzed. Sixty A. baumannii isolates each from a different patient were identified. The Charlson Comorbidity Index (≥3) was the greatest among patients with multi-drug resistance (MDR) compared to intermediate drug resistance (IDR) and pan-sensitive (PS) A. baumannii. The mean APACHE II scores for MDR, IDR and PS A. baumannii bacteremia were 21, 15 and 11, respectively (P < 0.05, MDR v. PS). Seventy-three percent of the isolates were resistant to quinolones, 44% to piperacillin/tazobactam, 45% to amikacin, 22% to imipenem, 0% to ticarcillin/clavulanate, and 0% to polymyxin. Among 28 patients with MDR A. baumannii bacteremia, 20 received inadequate empiric treatment, and 16 of these patients died (80%). Of the remaining eight patients with MDR bacteremia who received adequate empiric antibiotics, only two died (25%). The severity of underlying illness, degree of antibiotic resistance and receiving inadequate initial antibiotic therapy are associated with mortality among patients with bacteremia due to A. baumannii.

Increase in Bloodstream Infection Due to Vancomycin-Susceptible Enterococcus faecium in Cancer Patients: Risk Factors, Molecular Epidemiology and Outcomes

We conducted a prospective study to assess the risk factors, molecular epidemiology and outcome of bloodstream infection (BSI) due to Enterococcus faecium in hospitalized cancer patients. Between 2006 and 2012, a significant increase in vancomycin-susceptible E. faecium BSI was observed among cancer patients. Comparison of 54 episodes of BSI due to E. faecium with 38 episodes of BSI due to E. faecalis showed that previous use of carbapenems was the only independent risk factor for E. faecium acquisition (OR 10.24; 95% CI, 1.35-77.66). All E. faecium isolates were susceptible to glycopeptides, whereas 97% showed high-level resistance to ampicillin and ciprofloxacin. All 30 isolates available for genotyping belonged to the hospital-associated E. faecium lineages 17, 18 and 78. After 2009, most of the isolates belonged to ST117 (lineage 78). Patients with E. faecium BSI were more likely to receive inadequate initial empirical antibiotic therapy than patients with E. faecalis BSI, and time to adequate empirical antibiotic therapy was also longer in the former group. No significant differences were found between the two groups regarding early and overall case-fatality rates. Independent risk factors for overall case-fatality were current corticosteroids (OR 4.18; 95% CI, 1.34-13.01) and intensive care unit admission (OR 9.97; 95% CI, 1.96-50.63). The emergence of E. faecium among cancer patients is a concern since there are limited treatment options and it may presage the emergence of vancomycin-resistant enterococci. A rationale approach that combines infection control with antimicrobial stewardship.

Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients

Our aim was to identify the clinical profile of intensive care unit (ICU) patients with Pseudomonas aeruginosa (PA) pneumonia and the impact on ICU mortality and duration of mechanical ventilation (MV) of multidrug resistance (MDR) in the PA isolate and inadequate initial antibiotic therapy (IIAT). We conducted a retrospective analysis of data prospectively collected in the 18-bed general ICU of a major teaching hospital in Rome, Italy. The study cohort consisted of 110 adult patients with culture-confirmed PA pneumonia consecutively diagnosed in 2008-2010. ICU survivor and nonsurvivor groups were compared to identify factors associated with ICU mortality. In 42 (38 %) of the 110 cases of PA pneumonia analyzed, the PA isolate was MDR. Fifty-six (50.9 %) of the patients received IIAT, and 49 (44.5 %) died in ICU. In logistic regression analysis, IIAT, diabetes mellitus, higher Simplified Acute Physiology Score (SAPS) II scores, and older age were independently associated with ICU mortality. Among survivors, those who received IIAT or had MDR PA pneumonia had significantly longer median (interquartile ranges, IQR) periods of post-pneumonia onset MV (16.5 [14.5-20] and 15 [12-18] days, respectively) compared with those whose initial therapy was adequate (8 [6-13] days, P < 0.001) and those whose infections were caused by non-MDR PA (10.5 [6.5-13] days, P = 0.01). Our findings highlight the importance of IIAT as a risk factor for mortality in ICU patients with PA pneumonia. MDR in the PA isolate, like IIAT, can significantly increase the need for MV.

Luetic lymphadenopathy despite negative serology

Laboratory tests can be misleading for the diagnosis of syphilis and false-negative results are possible, but it is rare for both treponemal and non-treponemal tests to prove negative in different stages of the disease. We report on a case of luetic lymphadenopathy, diagnosed by histological examination and supported by immunohistochemical staining for Treponema pallidum, in the absence of skin lesions and positive serology. This case reminds us of how syphilis may present in many different clinical forms and that it should not be excluded only on the basis of negative serological tests. This patient's negative serology was probably due to inadequate initial antibiotic therapy. Given the current widespread use of antibiotics, greater consideration is warranted of the extent to which serological test results are modified by non-specific antibiotic therapies.

Sekundäre Peritonitis

There is some controversy regarding concepts currently propagated for an optimal surgical and antibiotic therapy in patients with secondary peritonitis and organ failure. It is not known whether the recent general progress in critical care ("Surviving Sepsis Campaign") has also improved outcome of this particular patient group. MEDLINE, EMBASE and Cochrane databases were non-systematically searched from 1985 through January 2010 using the words "source control", "peritonitis", "operation", "critical care" and "antibiotics". We also present experiences in corresponding high risk patients from our institution. The inability to obtain source control and an inadequate initial antibiotic therapy were -associated with a clearly higher mortality. De-pending on the initial intraoperative finding, planned and on demand relaparotomy do not conflict, but complement one another. The importance of the number of surgical revisions remains to be determined. Treatment after 2002 was associated with an improved prognosis. In contrast to source control, the mechanisms of increasing mortality with an inadequate initial antibiotic therapy remain controversial. Source control is the most important determinant for acute survival and has to be placed on top of the therapeutic priority list. The number of revisions needed to obtain source control, however, does not vary with survival and cannot guide decisions on therapy withdrawal or continuation. The recent prognostic improvement indicates the efficiency of new adjuvant therapeutic measures in unselected surgical high-risk patients.

Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients: risk factors, antibiotic therapy and outcomes

To assess the risk factors, antibiotic therapy and outcomes of multidrug-resistant Gram-negative bacilli (MDRGNB) bacteraemia in hospitalized patients with cancer. Episodes of MDRGNB bacteraemia were compared with a susceptible control group in a 4 year prospective study. Of 747 bacteraemias, 372 (49.7%) were caused by a Gram-negative bacilli (GNB). Fifty-one of these (13.7%) were caused by a multidrug-resistant (MDR) strain. Previous antibiotics [odds ratio (OR) 3.57; 95% confidence interval (CI) 1.63-7.80] and urinary catheter (OR 2.41; 95% CI 1.01-5.74) were identified as independent risk factors for MDRGNB acquisition. The most frequent mechanism of resistance was extended-spectrum β-lactamase (ESBL) production (45%), mainly by Escherichia coli, followed by Amp-C cephalosporinase hyperproduction (24%). Patients with MDRGNB bacteraemia more frequently received inadequate initial antibiotic therapy (69% versus 9%; P < 0.001) and time to adequate therapy was longer in this group (41% versus 4%; P < 0.001). Patients in the resistant group more frequently required intensive care unit (ICU) admission (14% versus 5%; P = 0.023), had greater need for mechanical ventilation (14% versus 3%; P = 0.005) and had a higher overall case-fatality rate (41% versus 21%; P = 0.003). Risk factors for mortality were solid tumour (OR 5.04; 95% CI 2.49-10.19), current corticosteroid use (OR 4.38; 95% CI 2.39-8.05), ICU admission (OR 11.40; 95% CI 3.19-40.74) and MDRGNB bacteraemia (OR 3.52; 95% CI 1.36-9.09). MDRGNB bacteraemia was common among cancer patients, especially in those exposed to antibiotics and urinary catheter. The most frequent mechanism of resistance was ESBL production. Patients with MDRGNB more frequently received inadequate empirical antibiotic therapy and presented poorer outcomes with a higher overall case-fatality rate (within 30 days).