Professional Documents
Culture Documents
Eyal Zimlichman, MD, MSc1,2; Daniel Henderson, MD, MPH1; Orly Tamir, PhD, MSc, MHA1; Calvin Franz, PhD3; Peter Song, BSE1; Cyrus K. Yamin, MD1,4; Carol Keohane, BSN, RN1,5; Charles R. Denham, MD6; David W. Bates, MD, MSc1,7
The total annual costs for the 5 major infections were $9.8 billion (95% CI, $8.3-$11.5 billion), with surgical site infections contributing the most to overall costs (33.7% of the total), followed by ventilator-associated pneumonia (31.6%), central lineassociated bloodstream infections (18.9%), C difficile infections (15.4%), and catheter-associated urinary tract infections (<1%).
02, 2013
To expect that all patients undergoing major surgery can have unflawed outcomes is not realistic. Surgery is performed by humans on humans and always will have complications such as nosocomial infections. Despite the progress in surgery and anaesthesia, the risk of developing nosocomial infections remains a real threat as more patients of greater age and with more co-morbidity are to be operated on
Ventilator-associated pneumonia in patients undergoing major heart surgery: an incidence study in Europe
Javier Hortal1*, Patricia Muoz26, Gregorio Cuerpo3, Hector Litvan4, Peter M Rosseel5,Emilio Bouza26, the European Study Group on Nosocomial Infections and the European Workgroup of Cardiothoracic Intensivists Critical Care 2009, 13:R80 doi:10.1186/cc7896
Patients undergoing major heart surgery (MHS) represent a special subpopulation at risk for nosocomial infections. Postoperative infection is the main noncardiac complication after MHS and has been clearly related to increased morbidity, use of hospital resources and mortality
Incidence of nosocomial infections among 971 patients undergoing major heart surgery in Europe.
BACT = bacteraemia; CRBI = catheter-related bloodstream infection; MEDIAST = postsurgical mediastinitis; SWI = surgical wound infection; TB = tracheobronchitis; UTI = urinary tract infection; VAP = ventilator-associated pneumonia. Hortal et al. Critical Care 2009 13:R80 doi:10.1186/cc7896
Definitions
NOSOCOMIAL INFECTIONS
Infection in a hospitalized patient Not present or incubating on admission
Incidence of VAP
Kollef et al. reported incidences of NP of 21.6% in patients admitted to a cardiothoracic ICU, 14% in other surgical ICU, and 9.3% in a medical ICU.
Ventilator-associated pneumonia in patients undergoing major heart surgery: an incidence study in Europe
Javier Hortal, Patricia Muoz, Gregorio Cuerpo, Hector Litvan, Peter M Rosseel, Emilio Bouza, the European Study Group on Nosocomial Infections and the European Workgroup of Cardiothoracic Intensivists
Critical Care 2009, 13:R80 doi:10.1186/cc7896
Key messages One or more nosocomial infections were detected in 4.4% of the patients. VAP was the most frequent nosocomial infection (2.1%, 13.9 episodes per 1000 days of mechanical ventilation). The principal microorganisms responsible for VAP in this study were: Enterobacteriaceae (45%),Pseudomonas aeruginosa (20%) and methicillin-resistant Staphylococus aureus (10%). Risk factors for VAP were: ascending aorta surgery, number of blood units transfused and need for re-intervention. Death was significantly more frequent in patients with VAP
(35% vs 2.3%).
Use and care of urinary catheters Use and care of vascular access lines Therapy and support of pulmonary functions Surveillance of surgical procedures Hand hygiene and standard precautions
Pneumonia types The 2005 ATS/IDSA guidelines distinguish the following types of pneumonia:
Hospital-acquired (or nosocomial) pneumonia (HAP) is pneumonia that occurs 48 hours or more after admission and did not appear to be incubating at the time of admission. Ventilator-associated pneumonia (VAP) is a type of HAP that develops more than 48 to 72 hours after endotracheal intubation.
Healthcare-associated pneumonia (HCAP) is defined as pneumonia that occurs in a non-hospitalized patient with extensive healthcare contact, as defined by one or more of the following:
Intravenous therapy, wound care, or intravenous chemotherapy within the prior 30 days Residence in a nursing home or other long-term care facility Hospitalization in an acute care hospital for two or more days within the prior 90 days Attendance at a hospital or hemodialysis clinic within the prior 30 days
Additional measures which might be helpful in distinct settings and populations continuous aspiration of subglottic secretions endotracheal tubes coated with antiseptics preference of heat-moisture exchangers (HMEs) over heater humidifiers (HH) oral decontamination selective decontamination of the digestive tract (SDD)
Guidelines for the management of adults with hospitalacquired, ventilator-associated, and healthcareassociated pneumonia
Am J Respir Crit Care Med 2005;171:388416
Antibiotic therapy
In patients with pneumonia, a lack of appropriate antimicrobial therapy is associated with increased mortality There is clear evidence that antibiotic therapy should be given early to improve survival A strong association between the administration of inappropriate antibiotic therapy and mortality has also been described in VAP Archives Internal Med 2004:164:637-644 Chest 2002; 122:262-268 AJRCCM 1997; 156:196-200
Relationship between the delay of antibiotic administration after the onset of shock and mortality of patients in septic shock Curr Opin Crit Care, Volume 13(5).October 2007.586591
Common Infectious Causes of Fever in the ICU Infectious Causes VAP Sinusitis Catheter-related sepsis Primary Gram-negative septicemia C difficile diarrhea Abdominal sepsis Complicated wound infections
Survival Rates
Logistic regression analysis: MRSA was the only independent risk factor for increased mortality, P=0.04
Supporting Evidence
Colonization of the oropharynx contributes to VAP Growth of pathogenic bacteria in dental plaque provides a breeding ground for microorganisms that produce VAP.
Devices Invasive ventilation Duration of invasive ventilation Reintubation Medication Prior antibiotic treatment Sedation
Nosocomial Pneumonia
Cumulative incidence = 1-3% per day of intubation Early onset (first 3-4 days of mechanical ventilation) Antibiotic sensitive, community organisms (S. pneumoniae, H. influenzae, S. aureus) Late onset Antibiotic resistant, nosocomial organisms (MRSA, Ps. aeruginosa, Acinetobacterspp, Enterobacterspp)
PREDISPOSING FACTORS Endotracheal intubation ICU Antibiotics Surgery Chronic lung disease Advanced age immunosuppression
ETIOLOGY
Early Onset (10%)-represent community acquired pathogens -Strep pneumoniae, H. influenza, Moraxella catarrhalis Late onset (80%)-typical hospital flora -gram negative aerobes -E. coli, Klebsiella, Pseudomonas -S. aureus
Supporting Evidence
Microorganisms in the mouth translocate and colonize the lung. Dental plaque can be removed by brushing. The American Dental Association recommends that healthy people brush teeth twice daily to remove plaque. Use of an oral care protocol reduces oral inflammation and improves oral health.
Chlorhexidine Evidence
Oral rinse reduced respiratory infections in cardiac surgery patients Reduced nosocomial pneumonia in patients intubated >24 hours. In a more varied ICU population, no difference was observed in VAP, mortality, or length of stay.
Chlorhexidine Evidence
A 2005 meta-analysis found no significant reduction in the incidence of hospitalacquired pneumonia or mortality rate. The CDC guidelines recommend use only during the perioperative period for adult cardiac surgery patients; routine use is not recommended.
Etiology: A typical feature of contemporary NI is that their etiological agents are opportunistic microorganisms that are a part of patient's own microbial flora. Up to 50 % of NI in the last decades are caused by Gram-negative microorganisms from the family Enterobacteriaceae, genus Escherichia, Klebsiella, Enterobacter, Serratia, Proteus, Providencia; genus Pseudomonas and Acinetobacter from the group of Gramnegative non-fermenting aerobes.
NI etiological agents are characterized by significant stability in surrounding environment. Gram-positive cocci can stand dehydration for long periods on surfaces, while Gramnegative survive in humid conditions for months.
Nowadays major prerequisites for the appearance and development of NI are the following: Constantly increasing stream of patients in health care institutions as a result of population aging, chronic diseases, accessibility of medical care, broadened health culture. Hospital overpopulation Concentration of multiple sources of infection and circulation of "hospital strains" of microorganisms
-air -dust -IV fluids & catheters -washbowls -bedpans -endoscopes -ventilators & respiratory equipment -water, disinfectants etc
Nosocomial Pneumonia
Cumulative incidence = 1-3% per day of intubation -Early onset (first 3-4 days of mechanical ventilation) Antibiotic sensitive, community organisms (S. pneumoniae, H. influenzae, S. aureus) -Late onset Antibiotic resistant, nosocomial organisms (MRSA, Ps. aeruginosa, Acinetobacterspp, Enterobacterspp)
Epidemiology of VAP
1844 patients after major heart surgery (Madrid) 140 VAP (7.6%; 22.2 per 1000 days of MV) mortality 45.7% vs 2.8% LOS 25.5 days vs 3 days 106 VAP (45.9%) mortality 54.7% vs 34.4% 231 patients after major heart surgery MV > 48h Hortal J et al. ICM 09; 35:1518-25
PREDISPOSING FACTORS Endotrachealintubation!!!!!!!!!!!!!! ICU Antibiotics Surgery Chronic lung disease Advanced age immunosuppression
PATHOGENESIS
Routes of invasion to LRT
Aspiration of oropharyngealorganisms (most common) Ventilated patients: leakage of bacteria around cuffupper airway colonization, tracheobronchitis Inhalation of infected aerosols (less common)
Hematogenous
Definitions of VAP
VAP was defined according to the following criteria : - Chest X-rays exhibiting lung infiltrates; - Temperature >38C or leukocyte count >12,000/mm3 or <4,000/mm3; - One of the following: 1) sputum modification, 2) suggestive auscultation, 3) low oxyhaemoglobin saturation, or 4) increased pulmonary oxygen consumption; - And one of the following: 1) directed broncho-alveolar lavage (BAL)positive culture at a threshold of 104 cfu/ml in BAL or 103 cfu/ml in mini-BAL , 2) fibreoptic bronchoscopy specimen-positive culture at a threshold of 106 cfu/ml, or 3) one of the following: positive pleural or blood cultures without any other site of infection, pulmonary or pleural abscess, histopathological evidence of pneumonia or cultures positive for specific agents
Pseudomonas Strept. pneumoniae. aeruginosa. Hemophilus Acinetobacter. influenzae. Enterobacter sp. Moraxella catarrhalis. MRSA. Anaerobes (uncommon).
Bouza E, Perez A, Munoz P, Jesus Perez M, Rincon C, Sanchez C, MartinRabadan P, Riesgo M: Ventilator-associated pneumonia after heart surgery: A prospective analysis and the value of surveillance. Crit Care Med 2003, 31:1964-1970.
Microorganisms causing VAP vary considerably according to the characteristics of the patients in the different ICU types, the length of hospital stay and intubation. Common pathogens include P. aeruginosa, S. aureus and Enterobacteriaceae . There is no evidence that the microorganisms causing VAP after cardiac surgery are substantially different to those in other types of patients in ICUs.
previously
Selection of initial appropriate therapy (i.e., getting the antibiotic treatment right the first time) is an important aspect of care for hospitalized patients with serious infections.
The most common pathogens include: P. aeruginosa, Acinetobacter species, K. pneumoniae, Enterobacter species, and MRSA
http://www.atsjournals.org/doi/full/10.1164/rccm.200405-644ST
Aerosolized antibiotics have not been proven to have value in the therapy of VAP (Level I) (256). However, they may be considered as adjunctive therapy in patients with MDR gram-negatives who are not responding to systemic therapy (Level III)
Duration of Therapy:
Efforts should be made to shorten the duration of therapy from the traditional 14 to 21 days to periods as short as 7 days, provided that the etiologic pathogen is not P. aeruginosa, and that the patient has a good clinical response with resolution of clinical features of Infection.
(American Thoracic Society, 2005)
Oxygenation
Purulent secretions
CXR infilterates
Unresolved HAP
Clinical re-assessment of the patient . Consider differential diagnosis . Exclude another site of infection ( UTI, vascular lines, bed sores, wounds). Re-collect another samples ( ET aspirate, bronchoscopic, pleural fluid, blood). Use multiple antibiotics instead of monotherapy. Consider steroids and open lung biopsy.
Avoid intubation and reintubation Prefer non-invasive ventilation Prefer orotracheal intubation & orogastric tubes Continous subglottic aspiration Cuff pressure > 20 cm H2O Avoid entering of contaminate condensate into tube/nebulizer Use sedation and weaning protocols to reduce duration Use daily interruption of sedation and avoid paralytic agents -
Hand Hygiene is the single most effective intervention to reduce the cross transmission of nosocomial infections
Handwashing must be "bacteriologically effective" wash hands before any procedure in which gloves and forceps are necessary after contact with infected patient or one colonised with multi-resistant bacteria after touching infective material use soap and water (preferably disinfectant soap) more prolonged and thorough scrub before surgery
A. Initial Resuscitation 1. Protocolized, quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion (defined in this document as hypotension persisting after initial fluid challenge or blood lactate concentration 4 mmol/L). Goals during the first 6 hrs of resuscitation: a) Central venous pressure 812 mm Hg b) Mean arterial pressure (MAP) 65 mm Hg c) Urine output 0.5 mL/kg/hr d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively (grade 1C). 2. In patients with elevated lactate levels targeting resuscitation to normalize lactate (grade 2C).
C. Diagnosis
1. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s) (grade 1C). At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted (grade 1C). 2. Use of the 1,3 beta-D-glucan assay (grade 2B), mannan and anti-mannan antibody assays (2C), if available, and invasive candidiasis is in differential diagnosis of cause of infection. 3. Imaging studies performed promptly to confirm a potential source of infection (UG).
D. Antimicrobial Therapy 1. Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C) as the goal of therapy. 2a. Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis (grade 1B).
2b. Antimicrobial regimen should be reassessed daily for potential deescalation (grade 1B).
3. Use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection (grade 2C).
4a. Combination empirical therapy for neutropenic patients with severe sepsis (grade 2B) and for patients with difficult-to-treat, multidrug-resistant bacterial pathogens such as Acinetobacter and Pseudomonas spp. (grade 2B). For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia (grade 2B). A combination of betalactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections (grade 2B). 4b. Empiric combination therapy should not be administered for more than 35 days. Deescalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known (grade 2B). 5. Duration of therapy typically 710 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia (grade 2C).
6. Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin (grade 2C). 7. Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause (UG).
E. Source Control 1.A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible (grade 1C).
2.When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred (grade 2B).
3.When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess) (UG).
4.If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established (UG).
F. Infection Prevention
1.Selective oral decontamination and selective digestive decontamination should be introduced and investigated as a method to reduce the incidence of ventilatorassociated pneumonia; This infection control measure can then be instituted in health care settings and regions where this methodology is found to be effective (grade 2B).
2.Oral chlorhexidine gluconate be used as a form of oropharyngeal decontamination to reduce the risk of ventilator-associated pneumonia in ICU patients with severe sepsis (grade 2B).
The last few years have been characterized by the emergence of certain Gram- negative bacteria, especially Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, which are resistant to almost all currently available antibiotics, except colistin.
Pseudomonas 26.4%
Acinetobacter 65.9%
Pharmacokinetics
CMS 3 millions IU every 8 h
Mathematic model:
Loading dose: 9 million UI and then 4,5 million UI every 12 h Loading dose: 12 million UI and then 4,5 million UI every 12 h
12 MUI loading and 4,5 MUI every 12 h
3 MUI la 8 ore
Population Pharmacokinetic Analysis of Colistin Methanesulfonate and Colistin after Intravenous Administration in Critically Ill Patients with Infections Caused by GramNegative Bacteria
a fraction of CMS is absorbed and is then partially converted into colistin within the systemic circulation another fraction of CMS dose is converted into colistin within the lungs and is then partially absorbed within the systemic circulation
- small clinical trials in VAP and NP ( 120-150 pts) - CMS + nebulized CMS versus i.v. CMS alone: clinical cure 79.5% vs.60.5% (p = 0.025). Korbila IP, Falagas ME : 2010 Clin Microbiol Infect 16:1230-1236 - Carbapenems + CMS + nebulized CMS sv. ATB alone: No effect on clinical cure
Rattanaumpawan P et al: 2010 J Antimicrob Chemother 65:2645-2649
Nebulized COLISTIN
In vitro : - colistin acts synergistically with other antibiotics - most frequently combined : rifampicin and carbapenems. - all studies: synergy with rifampicin against P. Aer.and A. baumannii
Combination Therapy
In vivo : - a few clinical studies have investigated CMS in combination therapy. - in critically ill patients are scant, great variability, low number pts. - all are retrospective !
a recent study performed in 258 patients (A. baumannii, P. aeruginosa and K. pneumoniae) combination therapy was not superior to colistin alone!
Falagas ME et al: 2010 J Antimicrob Agents 35:194-199
Factori de risc: Vrsta naintat Preexistena afectrii renale Hipoalbuminemia Utilizarea concomitent a antinflamatoarelor nesteroidiene Utilizarea vancomicinei
Reversibilitatea afectrii renale peste 88% n studiile care au monitorizat pacienii un interval de 1-3 luni
Riscul de nefrotoxicitate este mai redus dect cel raportat n litaratura anilor 70 80 prin:
Reducerea impuritilor colistimetatului sodic Monitorizarea atent i echilibrarea hidroelectrolitic n seciile de terapie intensiv Evitarea asocierii cu medicamente cu risc nefrotoxic
Multiple evidene referitoare la aciunea superioar a combinaiilor cu colistina cel mai frecvent cu carbapeneme Avantajele asocierilor de antibiotice
Lrgirea spectrului de activitate Creterea vitezei de bactericidie Evitarea seleciei de tulpini rezistente