The clinical implication and prognostic predictors of Tigecycline treatment for pneumonia involving multidrug-resistant Acinetobacter baumannii

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1 Journal of Infection (2011) 63, 351e361 The clinical implication and prognostic predictors of Tigecycline treatment for pneumonia involving multidrug-resistant Acinetobacter baumannii R 陳南丞 VS 余文良醫師 本檔僅供內部教學使用檔案內所使用之照片之版權仍屬於原期刊公開使用時, 須獲得原期刊之同意授權

2 Introduction Acinetobacter: aerobic, G (-), nonmotile rods, nonfermentative, catalase (+), oxidase (-) A. baumannii: glucose-oxidizing, non-hemolytic MDRAB: resistant to penicillins, cephalosporins, aztreonam, fluoroquinolones, aminoglycosides, carbapenems

3 Introduction Tigecycline: Tetracylin species, multiple resistance (MRSA, PRSA, VRE ), Rickettsiae, Chlamydia, Legionella, Mycobacteria Tigecycline for MDRAB involving carbapenem-r (?)

4 Introduction U.S. FDA higher mortality with Tigecycline than other antimicrobials in VAP. Study report lower cure rates with Tigecycline than imipenem in VAP (47.9% vs.70.1%)

5 Introduction Study report (murine pneumonia) Tigecycline decreased bacterial counts, not mortality for Imipenem-S or Imipenem-I AB Objectives: clinical implication and predictors of failure to Tigecycline for pneumonia involving MDRAB including carbapenem-r

6 Materials and methods Setting: CGMH- Linkou, 3000-bed, medical center with 308 ICU

7 Materials and methods Study design, patients and treatment /8 to 2010/3 for 2.5 years - Age> 18 years - Tigecycline for pneumonia involving MDRAB - Susceptibility testing to CLSI interpretive criteria for disk diffusion method, Etest method on Mueller-Hinton agar, MIC - MDRAB: AB with full or intermediate resistance to amikacin, gentamicin, cefepime, ceftazidime, piperacillin, piperacillintazobactam, aztreonam, ciprofloxacin and carbapenems.

8 Materials and methods Study design, patients and treatment - Dx of pneumonia: ATS and IDSA-- CxR, infection sign (temporature, WBC, decline in oxygenation and increasing purulent sputum) - Pneumonia with MDRAB - Tigecycline treatment for at least 7 days, with 100-mg loading dose followed by 50 mg q12h - Combination therapy - Delayed Tigecycline treatment

9 Demography and comorbidity Age, sex, and co-morbid illness Co-morbid illness - hepatic dysfunction - renal insufficiency - chronic pulmonary disease - heart disease - diabetes mellitus - immune compromise - hematological or solid organ malignancy - surgery - other infections

10 Clinical conditions and outcomes Mechanical ventilation CxR Vital sign APACHE II score 30-day mortality Clinical resolution of pneumonia - (1) improvement of pneumonia by F/U CxR - (2) survival with stationary CxR and afebrile status

11 Microbiology Pathogens, growth sites, susceptibility Microbial eradication: cultures negative for MDRAB, no growth or change of susceptibility profile of AB Initial bacteremia: B/C (+) from one week before to 3 days after Tigecycline Tx Bacteremia during Tigecyclinenm Tx: B/C (+) from 3 days after to end of Tigecycline Tx

12 Statistical methods SPSS X2 test or Fisher exact test Kolmogorove-Smirnov test Student s t- test or Manne-Whitney U test Odd ratios (ORs) and 95% confidence interval (CI) P< 0.05

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14 Result 116 episodes 112 p t 4 p t Tigecyclin Tx twice with separating at least 1 month 2 p t fail at 2 episodes * 1 p t expired at 2nd episode 2 p t resolution at 2 episodes 88 episodes tracheal aspirate cultures positive for MDRAB 28 episodes sputum cultures positive for MDRAB

15 Demography and comorbidity

16 Clinical conditions, etiologic pathogens of pneumonia, and treatment

17 Microbiological outcomes

18 Clinical outcomes

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20 Cases with initial bacteremia

21 Bacteremia during tigecycline treatment

22 * Higher APACH II score * Shorter intervals of TG use * Female * Monomicrobial MDRAB * Bilateral pneumonia

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24 Model A: including monomicrobial MDRAB pneumonia * Female * Malignancy * Higher APACH II score * Bilateral pneumonia * Monomicrobial MDRAB

25 Model B: including monomicrobial MDRAB pneumonia * Female * Malignancy * Bilateral pneumonia

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27 Predictors for the 30-day mortality Higher APACH II score Lower rate of polymicrobial pneumonia with GPC coinfction Hepatic dysfunction Bilateral pneumonia Bacteremic during TG Tx Deterioration of pneumonia on CxR Febrile status at the end of TG Tx Combination therapy (particular with carbapenems)

28 Clinical resolution rates of monomicrobial and polymicrobial pneumonia Monomicrobial vs. polymicrobial (45.2/ 65.9%, p= 0.044) For monomicrobial episodes (31) Monotherapy vs. combination therapy (44.4/ 45.5%, p=1.000) For polymicrobial episodes (85) Monotherapy vs. combination therapy (62.9/ 68%, p=0.623)

29 Discussion Monomicrobial MDRAB pneumonia: lower clinical resolution rate Better outcome for Tigecycline mono- or combination therapy in polymicrobial pneumonia due to better coverage for coexisting non-mdr MDRAB could be the most likely causative pathogen in monomicrobial pneumonia The overall efficacy of Tigecycline in treating MDRAB pneumonia was overestimated

30 Discussion Schafer et al.: 84% resolution rate in 25 p t with tigecycline-treated MDRAB VAP and/or bacteremia (80% combination therapy, 20% monotherapy with 100% resolution rate) Curcio et al: 1. 69% success rate in 29 p t with carbapenem- resistant MDRAB Tigecycline-treated VAP 2. 70% success rate in 44 p t with carbapenem-susceptible MDRAB Tigecycline-treated VAP

31 Discussion Poulakou et al.: 88.2% resolution rate in 17 cases with MDRAB pneumonia with Tigecycline monotherapy Gordon et al.: 68% resolution rate in 34 p t with carbapenem- resistant MDRAB with Tigecycline-treated infections (20 with MDRAB pneumonia and/or bacteremia, 19 with combination therapy)

32 Discussion Limitations - 1. distinguish airway MDRAB infections from colonization - 2. clinical inpact of other etiologic pathogens or extrapulmonary infections - 3. efficacy of Tigecycline monotherapy not well defined due to a high rate of combination therapy

33 Conclusion Tigecyclin monotherapy should be avoided when the other therapeutic options were available Polymicrobial pneumonia had higher clinical resolution rate than monomicrobial pneumonia For polymicrobial, combination therapy may offer better coverage than Tigecyclin monotherapy

34 Conclusion High disease severity, bilateral pneumonia, monomicrobial MDRAB pneumonia predicted failure of clinical resolution Deterioration of pneumonia predicted mortality.

35 Thanks for your attention