Adequate Initial Antibiotic Therapy Research Articles

Biomarkers kinetics in the assessment of ventilator-associated pneumonia response to antibiotics - results from the BioVAP study

PurposeOur aim was to evaluate the role of biomarker kinetics in the assessment of ventilator-associated pneumonia (VAP) response to antibiotics. Materials and methodsWe performed a prospective, multicenter, observational study to evaluate in 37 microbiologically documented VAP, the kinetics of C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM). The kinetics of each variable, from day 1 to 6 of therapy, was assessed with a time dependent analysis comparing survivors and non-survivors. ResultsDuring the study period kinetics of CRP as well as its relative changes, CRP-ratio, was significantly different between survivors and non-survivors (p=0.026 and p=0.005, respectively). On day 4 of antibiotic therapy, CRP of survivors was 47% of the initial value while it was 96% in non-survivors. The kinetics of other studied variables did not distinguish between survivors and non-survivors. In survivors the bacterial load also decreased markedly. Adequate initial antibiotic therapy was associated with lower mortality (p=0.025) and faster CRP decrease (p=0.029). ConclusionsC-reactive protein kinetics can be used to identify VAP patients with poor outcome as soon as four days after the initiation of treatment. (Trial registration - NCT02078999; registered 3 August 2012).

Long-term effect of computer-assisted decision support for antibiotic treatment in critically ill patients: a prospective ‘before/after’ cohort study

ObjectivesAntibiotic resistance has risen dramatically over the past years. For individual patients, adequate initial antibiotic therapy is essential for clinical outcome. Computer-assisted decision support systems (CDSSs) are advocated to support...

SP27-2 Treatment for healthcare associated pneumonia

SP27-2 Treatment for healthcare associated pneumonia W.-H. Sheng*. National Taiwan University Hospital, Taiwan Hospital acquired pneumonia (HAP) is one of the leading cause of healthcare associated infections in intensive care units (ICU). Ventilator-associated pneumonia (VAP) is the most common type of HAP. Patients who acquire HAP/VAP have higher mortality rates and longer ICU and hospital stays. HAP/VAP also is characterized with severe underlying systemic diseases and causative pathogens of multi-drug resistance, such as methicillin-resistant Staphylococcus aureus , Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae. Delayed administration of adequate antibiotic therapy is linked to an increased mortality rate. Therefore, the initial antibiotic therapy should be to rapidly provide coverage for all likely pathogens and to then narrow the antibiotic spectrum based on the results of quantitative cultures by bronchoscopic examination. The optimal antibiotic strategy for the treatment of HAP remains controversial. According to the ATS/IDSA guideline, initial treatment for mild– moderate HAP without risk for multidrug resistant microorganisms (MDRO), a fluoroquinolone (levofloxacin or moxifloxacin), or amoxicillin/clavulanate plus a macrolide has been suggested. For patients with severe HAP/VAP, late onset of VAP, with risk for MDRO, an antipseudomonal cephalosporin (cefepime, ceftazidime), or an antipseudomonal carbapenem (imipenem, meropenem), or a b-lactam/b-lactamase inhibitor (piperacillin/tazobactam) plus an antipseudomonal fluoroquinolone (levofloxacin, ciprofloxacin), or an aminoglycoside (amikacin, gentamicin, tobramycin) plus either linezolid or vancomycin is suggested. Clinical improvement usually takes 48 to 72h, therefore, unless the patient is declining clinically, antibiotics should not be modified during this time unless dictated by the results of microbiologic sensitivity. Eight days of antibiotic therapy appears equivalent to 15 daysof therapy except when treating non-glucose fermenting Gram-negative bacteria. A guideline-based approach using the local hospital or ICU antibiogram can increase the likelihood that adequate initial antibiotic therapy is used and reduce the overall use of antibiotics and the associated selection pressure for MDRO. In conclusion, a systematically applied strategy that addresses early intervention with broad-spectrum antibiotics based on the risks for MDRO, and which is appropriate to the local antibiogram, can improve outcomes. This strategy also includes quantitative culture of respiratory secretions, de-escalation of antibiotic therapy once culture results are available, and discontinuation of antibiotics after 8 daysof treatment in patients without Pseudomonas or Acinetobacter as the causative pathogens.

SP27-3 Treatment of noscomial pneumonia

SP27-2 Treatment for healthcare associated pneumonia W.-H. Sheng*. National Taiwan University Hospital, Taiwan Hospital acquired pneumonia (HAP) is one of the leading cause of healthcare associated infections in intensive care units (ICU). Ventilator-associated pneumonia (VAP) is the most common type of HAP. Patients who acquire HAP/VAP have higher mortality rates and longer ICU and hospital stays. HAP/VAP also is characterized with severe underlying systemic diseases and causative pathogens of multi-drug resistance, such as methicillin-resistant Staphylococcus aureus , Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae. Delayed administration of adequate antibiotic therapy is linked to an increased mortality rate. Therefore, the initial antibiotic therapy should be to rapidly provide coverage for all likely pathogens and to then narrow the antibiotic spectrum based on the results of quantitative cultures by bronchoscopic examination. The optimal antibiotic strategy for the treatment of HAP remains controversial. According to the ATS/IDSA guideline, initial treatment for mild– moderate HAP without risk for multidrug resistant microorganisms (MDRO), a fluoroquinolone (levofloxacin or moxifloxacin), or amoxicillin/clavulanate plus a macrolide has been suggested. For patients with severe HAP/VAP, late onset of VAP, with risk for MDRO, an antipseudomonal cephalosporin (cefepime, ceftazidime), or an antipseudomonal carbapenem (imipenem, meropenem), or a b-lactam/b-lactamase inhibitor (piperacillin/tazobactam) plus an antipseudomonal fluoroquinolone (levofloxacin, ciprofloxacin), or an aminoglycoside (amikacin, gentamicin, tobramycin) plus either linezolid or vancomycin is suggested. Clinical improvement usually takes 48 to 72h, therefore, unless the patient is declining clinically, antibiotics should not be modified during this time unless dictated by the results of microbiologic sensitivity. Eight days of antibiotic therapy appears equivalent to 15 daysof therapy except when treating non-glucose fermenting Gram-negative bacteria. A guideline-based approach using the local hospital or ICU antibiogram can increase the likelihood that adequate initial antibiotic therapy is used and reduce the overall use of antibiotics and the associated selection pressure for MDRO. In conclusion, a systematically applied strategy that addresses early intervention with broad-spectrum antibiotics based on the risks for MDRO, and which is appropriate to the local antibiogram, can improve outcomes. This strategy also includes quantitative culture of respiratory secretions, de-escalation of antibiotic therapy once culture results are available, and discontinuation of antibiotics after 8 daysof treatment in patients without Pseudomonas or Acinetobacter as the causative pathogens.

Diagnosis and management for urosepsis

Urosepsis is defined as sepsis caused by a urogenital tract infection. Urosepsis in adults comprises approximately 25% of all sepsis cases, and is in most cases due to complicated urinary tract infections. The urinary tract is the infection site of severe sepsis or septic shock in approximately 10-30% of cases. Severe sepsis and septic shock is a critical situation, with a reported mortality rate nowadays still ranging from 30% to 40%. Urosepsis is mainly a result of obstructed uropathy of the upper urinary tract, with ureterolithiasis being the most common cause. The complex pathogenesis of sepsis is initiated when pathogen or damage-associated molecular patterns recognized by pattern recognition receptors of the host innate immune system generate pro-inflammatory cytokines. A transition from the innate to the adaptive immune system follows until a T(H2) anti-inflammatory response takes over, leading to immunosuppression. Treatment of urosepsis comprises four major aspects: (i) early diagnosis; (ii) early goal-directed therapy including optimal pharmacodynamic exposure to antimicrobials both in the plasma and in the urinary tract; (iii) identification and control of the complicating factor in the urinary tract; and (iv) specific sepsis therapy. Early adequate tissue oxygenation, adequate initial antibiotic therapy, and rapid identification and control of the septic focus in the urinary tract are critical steps in the successful management of a patient with urosepsis, which includes early imaging, and an optimal interdisciplinary approach encompassing emergency unit, urological and intensive-care medicine specialists.

C reactive protein and procalcitonin as diagnostic markers of sepsis in febrile infants and children

Objective. The aim of this study was to estimate significance of determining C-reactive protein and procalcitonin for diagnosis of sepsis in febrile children. Methods. Data from medical history of 82 children (30 days to 16 years) who had been admitted into Intensive Care Unit of Pediatric Clinic, Clinical Centre 'Kragujevac', Kragujevac, were used in the study. The children were divided into two groups according to specific criteria for defining sepsis. Immediately after admission, we monitored erythrocyte sedimentation rate (ESR), leukocyte count, Creactive protein and procalcitonin, in different time intervals and their values were analyzed as indicators of disease control and success of the antibiotic therapy. Results. Sepsis was diagnosed in 47 (57.32%), localized respiratory and urinary tract infections in 35 (42.68%), and aseptic meningitis in 4 children. In the sepsis group the values of analyzed parameters were statistically higher than those in the control group, which showed similar values in both groups. The most sensitive parameter for diagnosis of sepsis was procalcitonin (sensitivity 87.2%), while ESR showed the least sensitivity (57.4%). The area under ROC curve for C-reactive protein was 0.699. Cut-off value for Creactive protein was 47.25 mg/l (sensitivity 76.6%, specificity 53.7%). The area under ROC curve for procalcitonin was 0.824. Cut-off value for procalcitonin was 2.69 ng/ml (sensitivity 87.2%, specificity 84.3%). The values of Creactive protein and procalcitonin decreased only after 24-48h with adequate initial antibiotic therapy. Conclusion. Procalcitonin and C-reactive protein are respectable indicators of sepsis in febrile children.

Urosepsis—from the view of the urologist

Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community-or nosocomial-acquired urinary tract infection (UTI). The underlying UTI is almost exclusively a complicated one with involvement of parenchymatous urogenital organs (e.g. kidneys, prostate). In urosepsis, as in other types of sepsis, the severity of sepsis depends mostly upon the host response. The urological management of urosepsis comprises early diagnosis, early fluid and oxygen treatment, early antibiotic therapy and early control of the complicating factor in the urinary tract. Time from admission to therapy is critical. The shorter the time to effective treatment, the higher is the success rate. This aspect has to become incorporated into the organisational process, including urologists, radiologists and intensive care specialists amongst others. Adequate initial antibiotic therapy has to be insured. This goal implies, however, a wide array of measures over time to ensure a rational antibiotic policy, including microbiologists and clinical pharmacologists. Dosage of an antibiotic in the septic patient generally has to be high to ensure adequate pharmacological exposure in the individual patient.

Epidemiology, treatment and prevention of healthcare-associated urinary tract infections

Healthcare-associated urinary tract infections (HAUTIs) are the most frequent healthcare-associated infections in general hospitals. They are almost exclusively complicated UTIs, although complicating factors are very heterogenous. HAUTIs are mainly catheter associated. Most of them are asymptomatic and do not need antimicrobial therapy. However, cross-contamination and cross-infection may contribute to distribution of resistant uropathogens. The bacterial spectrum of HAUTI is broad, and antibiotic resistance is common. The authors reviewed the literature from 2000 to 2010 to determine the epidemiology, prevention and best treatment strategies for HAUTI. The recommendations were summarized by determining the level of evidence and grading each recommendation. The treatment for HAUTI encompasses treatment for complicating factors as well as antimicrobial chemotherapy. At least in serious UTI, adequate initial antibiotic therapy results in lower mortality. Therefore, the initial antibiotic regimen must provide sufficient antibiotic coverage. This can only be achieved if the local or regional bacterial spectrum and antibiotic resistance patterns of uropathogens are followed continuously. Provisional microbiological findings, such as reports on Gram-stain or certain biochemical results, can lead to early stratification of pathogens and allow a more tailored empiric antibiotic therapy. Antibiotic therapy of HAUTI has to consider therapeutic success in the individual patient and prevention of emergence of antibiotic-resistant mutants. For both aspects, adequate drug selection and dosing are paramount. Antibiotic treatment for HAUTI should follow prudent antibiotic use to prevent emergence of antibiotic resistance.

Vascular graft infections in the intensive care unit: Clinical spectrum and prognostic factors

To report clinical characteristics and prognosis of vascular graft infections in Intensive Care Unit (ICU). Thirty seven patients consecutively admitted in ICU for suspected or definite vascular graft infection between January 2006 and June 2009 were included. Staphylococcus species (n=18) and enterobacteriae (n=16) were the most frequent causative organisms. Twenty six patients (70%) needed mechanical ventilation. Further surgical procedures were performed in 7 patients (19%). In case of definite infection, mortality in ICU was 33%. In non survivors, shock (92% vs 42%, p=0.01), age>70years (73% vs 27%, p=0.04), POSSUM score>45 (73% vs 27%, p=0.04) and extra-anatomic bypass (45% vs 14%, p=0.05) were more frequent, intra-operative volume of red cells transfusion (6±3 vs 3±2 units, p=0.006) and of fresh frozen plasma (2.8±2.8 vs 0.7±1.2 units, p=0.02), and SAPS II score (58±26 vs 38±17, p=0.03) were higher. Proportion of adequate initial antibiotic therapy was similar in survivors and non survivors (91% vs 100%, p=0.4). Proportion of patients treated with an aminoglycoside tended to be higher in survivors (59% vs 27%, p=0.07). By multivariate analysis, only shock was associated with death in ICU (AOR: 16.3; 95% CI: 1.7-152.1; p=0.01). Vascular graft infection carries high morbidity and mortality rates in ICU. Extra-anatomic bypass might be associated with higher mortality. Early aminoglycoside prescription might be protective.

Therapeutic challenges of urosepsis

Urosepsis accounts for approximately 25% of all sepsis cases and may develop from a community or nosocomial acquired urinary tract infection (UTI). The underlying UTI is almost exclusively a complicated one with involvement of parenchymatous urogenital organs (e.g. kidneys, prostate). In urosepsis, as in other types of sepsis, the severity of sepsis depends mostly upon the host response. The treatment of urosepsis comprises four major aspects: Early goal directed therapy, early optimal pharmacodynamic exposure to antimicrobials, early control of the complicating factor in the urinary tract and specific sepsis therapy. Following these prerequisites there appear two major challenges that need to be addressed: Firstly, time from admission to therapy is critical; the shorter the time to effective treatment, the higher the success rate. This aspect has to become incorporated into the organisational process. Secondly, adequate initial antibiotic therapy has to be insured. This goal implies however, a wide array of measures to ensure rational antibiotic policy. Both challenges are best targeted if an interdisciplinary approach at any level of the process is established, encompassing urologists, intensive care specialists, radiologists, microbiologists and clinical pharmacologists working tightly together at any time.

Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: Diagnosis and treatment

Background Ventilator-associated pneumonia (VAP) is an important cause of morbidity and mortality in ventilated critically ill patients. Despite a large amount of research evidence, the optimal diagnostic and treatment strategies for VAP remain controversial. Purpose The aim of this study was to develop evidence-based clinical practice guidelines for the diagnosis and treatment of VAP. Data sources include Medline, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Database of Systematic Reviews and Register of Controlled Trials. Study Selection The authors systematically searched for all relevant randomized controlled trials and systematic reviews on the diagnosis and treatment of VAP in mechanically ventilated adults that were published from 1980 to October 1, 2006. Data Extraction Independently and in duplicate, the panel critically appraised each published trial. The effect size, confidence intervals, and homogeneity of the results were scored using predefined definitions. The full guideline development panel arrived at a consensus for scores on safety, feasibility, and economic issues. Levels of Evidence Based on the scores for each topic, the following statements of recommendation were used: recommend, consider, do not recommend, and no recommendation because of insufficient or conflicting evidence. Data Synthesis For the diagnosis of VAP in immunocompetent patients, we recommend that endotracheal aspirates with nonquantitative cultures be used as the initial diagnostic strategy. When there is a suspicion of VAP, we recommend empiric antimicrobial therapy (in contrast to delayed or culture directed therapy) and appropriate single agent antimicrobial therapy for each potential pathogen as empiric therapy for VAP. Choice of antibiotics should be based on patient factors and local resistance patterns. We recommend that an antibiotic discontinuation strategy be used in patients who are treated of suspected VAP. For patients who receive adequate initial antibiotic therapy, we recommend 8 days of antibiotic therapy. We do not recommend nebulized endotracheal tobramycin or intratracheal instillation of tobramycin for the treatment of VAP. Conclusion We present evidence-based recommendations for the diagnosis and treatment of VAP. Implementation of these recommendations into clinical practice may lessen the morbidity and mortality of patients who develop VAP.

Spectrum and antibiotic resistance of uropathogens from hospitalised patients with urinary tract infections: 1994–2005

From 1994–2005, all uropathogens cultured from the urine of hospitalised urological patients were identified and their sensitivity was tested against the most important antibiotics for the treatment of urinary tract infection (UTI). Duplicate isolates were eliminated. The following results were obtained: (i) there was no general trend of increase in resistance; (ii) certain uropathogens developed resistance to some antibiotics; (iii) vancomycin- or linezolid-resistant staphylococci or enterococci did not play a role; (iv) the lowest overall rates of resistance were found with piperacillin/tazobactam; and (v) ciprofloxacin and trimethoprim/sulfamethoxazole showed the next favourable overall activity. Adequate initial antibiotic therapy is critical in the treatment of severe UTI. Therefore, ongoing surveillance of antibiotic resistance must be performed in every institution. Additionally, it reflects antibiotic and hospital infection policies in a defined department or institution.

Diagnosis and Treatment of Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the ICU. Patients who acquire VAP have higher mortality rates and longer ICU and hospital stays. Because there are other potential causes of fever, leukocytosis, and pulmonary infiltrates, clinical diagnostic criteria are overly sensitive in the diagnosis of VAP. Employing quantitative cultures of bronchopulmonary secretions in the diagnostic algorithm leads to less antibiotic use and probably to lower mortality. With respect to microbiologic diagnosis, it is not clear that the use of a particular sampling method (bronchoscopic or nonbronchoscopic), when quantitatively cultured, is associated with better outcomes. Delayed administration of adequate antibiotic therapy is linked to an increased mortality rate. Hence, the focus of initial antibiotic therapy should be to rapidly provide antibiotic coverage for all likely pathogens and to then narrow or focus the antibiotic spectrum based on the results of quantitative cultures. Eight days of antibiotic therapy appears equivalent to 15 days of therapy except when treating nonlactose-fermenting Gram-negative organisms. In this latter situation, longer treatment durations appear to reduce the risk of recrudescence after discontinuation of antibiotic therapy. A guideline-based approach using the local hospital or ICU antibiogram can increase the likelihood that adequate initial antibiotic therapy is used and reduce the overall use of antibiotics and the associated selection pressure for multidrug-resistant organisms.

Selection of an Empiric Antibiotic Regimen for Hospital-Acquired Pneumonia Using a Unit and Culture-Type Specific Antibiogram

The objective of this retrospective study was to determine the optimal initial antibiotic regimen for hospital-acquired pneumonia using the frequency and sensitivity of Gram negative microorganisms found in sputum cultures. An antibiogram was constructed and compared with the hospital intensive care unit (ICU) antibiogram. The results yielded 191 microorganisms. The study-generated antibiogram showed that the highest percent susceptible antibiotics for all Gram-negative microorganisms were imipenem (75%) and amikacin (84%). Considering only Pseudomonas aeruginosa, the study-generated antibiogram and the hospital ICU antibiogram showed similar results, piperacillin and amikacin (86% and 82%, respectively, vs 91% and 85%, P = nonsignificant for both). The optimal empiric antibiotic regimen in the surgical ICU is different if directed against all possible microorganisms as opposed to the most prevalent microorganism P aeruginosa. Determining initial empiric antibiotic therapy using an ICU and culture-type specific antibiogram would result in a greater likelihood that more patients would receive adequate initial antibiotic therapy.