Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Bakteriella Infektioner hos Neutropena Mats Kalin Infektionsklinken Karolinska universitetssjukhuset, Solna [email protected] Cytoreductive chemotherapy primarily affects cells with a high rate of division, like bone marrow cells and epithelial cells Mucous membranes are affected causing mucositis, which may be especially severe in the oral cavity, in the lower oesophagus and in the perianal region. Necrotising enterocolitis may also occur Mucositis may be aggravated by reactivation of Herpes simplex virus infection, which may affect all parts of the GI tract Also increased yeast colonisation of the GI tract may aggravate mucositis. Mucositis severely compromises the barrier function. Therefore, translocation of bacteria from the entire GI canal to the blood occurs with increased frequency In case of granulocytopenia (<0.5) bacteremia with signs and symptoms of sepsis will develop Blood stream Pathogens at the Center for Haematology, Karolinska hospital Candida spp 1.7 % 1988-2001 n=1402 Other Gramneg Stenotrophomonas maltophilia CNS Enterobacter spp Pseudomonas aeruginosa S.aureus Klebsiella spp Alpha-strept E.coli Cherif et al 2004 The Haematology J 4:240 Enterococci Other Pneumococci Grampos In addition to mucositis and granulocytopenia cancer chemotherapy will cause - T cell deficiencies - - for long time periods implying increased risks for infection w - intracellular bacteria, herpes viruses, PCP and other fungi - Ig-deficiency With risk for severe pneumococcal ao infections Steroids and other drugs may compromise macrophage function CNS has become the most common etiology in neutropenic fever due to the frequent use of CVCs Alpha-streptococci - are increasing in frequency as a cause of neutropenic fever - due to severe mucositis caused by e.g. high dose cytosin arabinoside. -The course may be fulminant with septic shock and ARDS Enterococci are increasing in many centers, especially E.faecium Infections in Neutropenic Cancer Patients • • • • • • The risk for bacterial infection is related to depth and length of neutropenia Bacteria are translocated from the GI tract GI flora may be affected by hospitalisation and ab therapy The course may be fulminant with septic shock Symptoms may be subtle due to lack of immune response Fever is the signal for risk of serious infection Broad-spectrum antibiotic therapy must be started immediately when a neutropenic patient presents with fever: - Cephalosporin with Pseudomonas activity - Carbapenem - Piperacillin/Tazobactam …. ..but only after blood cultures have been obtained • • • • • • before start of antibiotics 20 – 40 ml in 4-6 bottles, excluding anaerobic bottles? >1 venipuncture does not facilitate interpretation but if CVC or PAC is used peripheral specimen should also be obtained Time to positive results from CVC/PAC and peripheral sample, respectively, can be used to diagnose line infection Cultures should also be obtained from urine, wounds and airways Lamy et al 2002, CID 35:842 Ortiz & Sande 2000, Am J Med 108:445 DesJardin et al 1999, Ann Intern Med 131:641 Treatment of Infections in Neutropenic Cancer Patients Broad-spectrum antibiotic therapy must be started immediately when a neutropenic patient presents with fever: -Cephalosporin with Pseudomonas activity Ceftazidime (Cefepime) -Carbapenem Imipenem Meropenem -Piperacillin/Tazobactam Paul et al, JAC Dec 12, 2005 Monotherapy probably superior to combination therapy • Similar if not better survival rate • Lower treatment failure rate • Lower rate of adverse events • Similar rate of secondary infections (Cochrane 2003;(3):CDOO3038) Treatment of Neutropenic Fever • Cephalosporin with Pseudomonas activity Ceftazidime …………. 1 st choice G- (G+) (Cefepime) • Carbapenem ……………… 2 nd choice G- G+ Imipenem Meropenem • Piperacillin/Tazobactam …. 1 st choice G- G+ No advantage of combination with aminoglycoside - except for septic shock (?) - aminoglycoside alone insufficient Gramneg coverage Limited advantage of addition of - vancomycin…………………………… G+ Indications for Vancomycin • Clinically suspected serious CVC infection • Infection with multiresistant bacteria • Blood culture reported positive for Gram-pos bacteria in a patient with deteriorating condition before final identification and susceptibility report • Hypotension or other evidence of cardiovascular impairment and ?? - Severe mucositis - Quinolone prophylaxis - due to risk of infection with penicillin resistant alphastreptococci Hughes 2002 CID 34:730 (IDSA Guidelines) It is of decisive importance to follow the course closely Therapy may have to be changed as a results of • deteriorating general condition • new signs and symptoms of focal infection • results of cultures, most importantly blood cultures • results of chest X ray or other investigations Pulmonary Infiltrates in Neutropenic Patients Totally 1573 patients 1986-92 295 (17%) developed pulmonary infiltrates - 29 % microbiologically documented Complete Response - 61 % in patients with pulmonary infiltrates - 83 % in other documented infections Early deaths (<21 days): 22 % _________________________________________ Meschmeyer et al 1994, Medizinische Klinik 89:114 Cancer 73:2296 Annals Hematol 69:231 GI epithelial damage Bacteremia Increased GI yeast colonisation /focal infection Antibiotic therapy Yeast translocation Invasive yeast infection Invasive Fungal Infections in Cancer Patients intensity of chemotherapy and improved antibiotic therapy More patients surviving for longer periods with severe immune defects (?) Invasive Candidiasis Pneumocystis J Pneumonia (PCP) Improved Fungal Therapy, Prophylaxis, Other factors (?) mortality rate invasive candidiasis, especially C.albicans non-albicans Candida more patients with invasive aspergillosis more patients with uncommon fungal infections Clinical Condition after 72 h of Antibiotic Therapy Relation to Ultimate Outcome, n=1085 IMPROVING 25 % STABLE 65 % 10% 15% 46% 18% DETERIORATING 10 % Gbacteremia FUO 20% 39% 23% 33% CDI 25% G+ 21% % ultimately surviving 100 28% 90 bacteremia 22% 11 De Pauw & Intercontinental Study Group, Ann Intern Med 1994 FUO 89 episodes Afebrile after ab therapy 60 episodes antibiotics stopped 48h after defervescence 31 episodes Neutropenic when ab stopped 23 episodes Neutropenia resolved 8 episodes Fever relapsed 3 episodes Fever relapsed 2 episodes Success 20 episodes Success 6 episodes Cherif 2004, SJID 36:593 Failure 29 episodes antibiotics continued > 48h after defervescence 29 episodes Neutropenic when ab stopped 26 episodes Neutropenia had resolved 3 episodes Fever relapsed 6 episodes 2 patients died Success 20 episodes Success 3 episodes Observed and Predicted Rates of Fever Resolution - without serious complications - as a response to adequate ab therapy for neutropenic fever - in relation to points by the MASCC risk index score 8-16 17-18 19-20 21 n=71 67 67 172 22 52 23 102 24 25-26 127 98 Klastersky et al 2000, J Clin Oncol 18:3038 Characteristic Points Age < 60 y 2 No COPD 4 Solid tumor or no previous fungal dis 4 Burden of illness none or mild 5 or moderate 3 No dehydration 3 No hypotension 5 Outpatient status 3 Prospective evaluation of MASCC at Hem C Karolinska Low risk patients (105 episodes) Ineligible for oral therapy (38 episodes) eligible for oral therapy (67 episodes) Excluded Discherged with oral antibiotics 24 hours after defervescence Infection related mortality 2 patients Clinical assessment after 3 days Fever relapse readmission One patient • MASCC risk-index score < 21 (high risk): 176 pts (63%) w serious medical complications in 63% • > 21 (low risk) 105 pts w serious medical complications in 15% - and in an additional 21% other facts precluded oral therapy Continued afebrile 66 episodes Final evaluation after 4 weeks Fever relapse 2 patients one aspergillosis one pneumocyctis Afebrile (success) 64 patient No mortality Thus, a total of 24% of haematological patients with neutropenic fever could be discharged with oral therapy 24 h after Cherif et al 2006 defervescence, essentially w/o complications Haematologica 14 Quinolone consumption and resistance in Stockholm and at Karolinska Hospital 120 Per cent resistance 12 10 140 100 Quinolone consumption Stockholm area Quinolone resistance, P.aeruginosa 80 8 60 6 40 Quinolone consumption 4 Karolinska hospital Quinolone resistance, E.coli 2 20 0 0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 Years Sörberg et al 2002, Scand J Infect Dis 34:372 DDD/1000pcd or 1000DDD 16 Resistance problems according to ICU-”STRAMA” Gramneg enterobacteria Quinolones ESBL Enterobacter Cephalosporin Quinolones inducable resistance in high frequency 5-10 % Pseudomonas aeruginosa Imipenem Quinolones Ceftazidime Piperacillin 5-10 % rare findings 25 % 12 % 10 % 17 % Stenotrophomonas maltophilia Imipenem Quinolones Ceftazidime 100 % 30 % 10 % Hahnberger: http://e.lio.se/ivastrama/