重癥感染指導(dǎo)_圖文

1、 DefinitionsMDR A. baumannii was defined as resistance to at least two b-lactam antimicrobials (including ceftazidime, cefotaxime, cefepime, cefpirome, ampi-cillin-sulbactam, piperacillin-tazobactam, cefoperazone-sulbactam, gentamicin or amikacin, ciprofloxacin or ofloxacin, and trimethoprim-sulfame

2、thoxazole.Pan-drug-resistant (PDR A. baumannii was defined as: “resistance to all currently available antimicrobials except colistin or tigecycline by routine disk-diffusion method” (Falagas et al, 2006a.Empirical antimicrobial therapy was considered appropriate if the organism was susceptible in vi

3、tro to at least 1 of the drugs administered within 72 hours after the onset of bacteremia.Clinical outcomes were assessed 72 hours after the onset of bacteremia and defined as: 1 a complete response (ie, resolution of clinical sepsis;2 a partial response (ie, improvement of clinical sepsis without c

4、omplete resolu-tion; and 3 failure (ie, absence of resolu-tion, worsening of sepsis.Blood cultures were processed using the BacT/Alert automated culture system (Organon Teknika, Durnham, NC follow-ing the manufacturers instructions. A. bau-mannii isolates were identified by standard microbiological

5、techniques and antimicro-bial susceptibility testing was determined by the disk diffusion technique, in accor-dance with Clinical and Laboratory Stan-dards Institute criteria (NCCLS, 2000. Intermediate susceptibility to antibiotics was considered as having resistance. Ethical approvalThe study proto

6、col was approved by the Institutional Review Board of Khon Kaen University.Statistical analysisData analysis was performed using SPSS (SPSS, Chicago, IL, version 11.5. The Fishers exact or Pearsons chi-square tests were used to compare categorical variables, where appropriate.The Stu-dents t-test or

7、 Wilcoxon and Kruskal-Wallis tests were used to test for statisti-cal significance of continuous variables, where appropriate. Univariate analysis was used to identify significant factors; the results being presented as an odds ratio (OR with a 95% confidence inter-val (95%CI.Multiple logistic regre

8、ssion analysis, using the backward likelihood ratio selection method, was used to assess independent factors related to contracting MDR A. baumannii bacteremia and those related to mortality.A p-value 0.05 was considered statistically significant.RESULTSDuring the 3-year period of the study, there w

9、ere 84 episodes in 79 patients with positive blood cultures for A. baumannii, indicating an incidence of 7.8 cases per 10,000 hospital admissions.Among these, the incidences of MDR- and PDR- A. bau-mannii bacteremia were 3.6 and 1.8 cases per 10,000 hospital admissions, respec-tively.There was an in

10、creasing trend in antimicrobial resistance to several drugs during the 3-year study (Fig 1.Medical records were available for 65 cases (82.3%.Of these, 16 cases were excluded from the study due to contami-nation (6 cases, mixed infection (9 cases and transfer to another hospital (1 case. Among the r

11、emaining 49 cases, 25 (51% and 24 cases (49%, respectively, had non-MDR and MDR A. baumannii bacteremia and 15 of the 24 MDR A. baumannii cases (62.5% had PDR A. baumannii infection.The demographic data are presented in Table 1. The mean age of the two patient groups (ie, non-MDR and MDRCPOCAZCTXSAM

12、SCFPTZPIPMMEMOFX SXT20052006200720052006 2007AK NET CFX A. baumannii bacteremia were compa-rable 56.9 (SD, 17.5 vs 59.4 (SD, 16.8 years. There were no differences in sex distribution or admission wards. All pa-tients with MDR A. baumannii bacteremia, compared to two-thirds of those with non-MDR A. b

13、aumannii infection, had hospital-acquired infections (p =0.02. The majority of patients in the two groups had similar underlying diseases except for those with chronic kidney disease, for which the proportion of disease was significantly higher in patients with MDR A. baumannii bacteremia than those

14、 with non-MDR A. baumannii bacteremia (8 cases; 33.3% vs 2 cases; 8%, p =0.04. About two-thirds of thepatients in each group had secondary bac-teremia, of which pneumonia (20 cases; 40.8% was the most common source of bacteremia, followed by intra-abdominal infection (9 cases; 18.4%. There was no si

15、gnificant difference in the proportion of pneumonia between the two groups 7/25 (28% in non-MDR group vs 13/24 (54.2% in MDR group, p =0.08. Intra-abdominal infections, as a source of bacteremia, were found in 6 and 3 cases with non-MDR and MDR, respectively. The remaining sources of bacteremia were

16、 urinary tract, sinus, and skin /soft tissue infections, which were found in one case each in the non-MDR group.Fig 1Antimicrobial susceptibility patterns of A. baumannii isolated from patients with A. baumanniibacteremia during 2005-2007 at Srinakarin Hospital.AK, amikacin; NET, netilmicin; CFX, ci

17、profloxacin; OFX, ofloxacin; SXT, trimethoprim /sulfamethoxa-zole; CPO, cetriaxone; CAZ, ceftazidime; CTX, cefotaxime; SAM, ampicillin-sulbactam; SCFP , cefo-perazone /sulbactam; TZP , piperacillin-tazobactam; IPM, imipenem; MEM, meropenem Factors p-valueNon-MDR MDR A. baumannii A. baumannii(n =25 (

18、n =24No. of patients receiving appropriate empirical 21/22 (95.56/24 (25 <0.001 antibiotic within 72 hours of bacteremia (n =46aNo. of patients receiving appropriate antibiotic 23/24 (95.810/24 (41.7 <0.001 during the course of bacteremia (n =48aMedian (range duration from bacteremia to 0 (0-9

19、 2.5 (0-5 0.006 receiving appropriate antibiotic; days (n =33No. of patients alive at 72 hours of empirical treatment 19 (76 10 (41.70.02Median (range duration of hospitalization since 14 (2-86 21.5 (4-161 0.18 bacteremia; days (n =29Clinical outcomes at 72 hours of bacteremia (n =29 0.02Complete re

20、sponse 12/19 (63.2 1/10 (10 Partial response 2/19 (10.5 1/10 (10 Failure 5/19 (26.3 8/10 (80 Overall in-hospital mortality 12 (4822 (91.70.001Treatment and clinical outcomes in patients with non-MDR and MDR A. baumanniibacteremia.No. (% of cases aMissing data = patients received an antibiotic for wh

21、ich the susceptibility pattern was not known.The proportions of patients who received appropriate empirical antimi-crobial therapy and appropriate anti-microbial therapy during the course of bacteremia were significantly lower in patients with MDR A. baumannii bacte-remia (25% vs 95.5%, p <0.001;

22、 41.7% vs 95.8%, p <0.001; respectively (Table 2. The median (range duration from the onset of bacteremia to receipt of appropriate anti-microbial therapy was significantly longer in patients with MDR A. baumannii bacte-remia 2.5 (0-5 vs 0 (0-9 days, p =0.006. Seventy-two hours after the onset of

23、 bac-teremia, there was a significantly lower proportion of patients who survived with MDR A. baumannii bacteremia (41.7% vs 76%, p =0.02. Of the 29 patients surviv-ing at 72 hours; there was a significantly greater proportion with worse outcomesDISCUSSIONMDR A. baumannii has become a seriousnosocom

24、ial pathogen causing a variety of clinical manifestations.Nosocomial septicemia is one of the most important problems facing modern medicine.Pa-tients with MDR A. baumannii bacteremia have higher mortality and medical costs than non-MDR A. baumannii bacteremia patients. These bacteria must be identi

25、-fied quickly in order to adjust empirical treatment (Lee et al, 2007; Sunenshine et al, 2007.In a case-control study, Shih et al (2008 found four independent risk factors associated with multidrug resistance in A. baumannii septicemia:previous coloniza-tion with A. baumannii, antecedent antimi-crob

26、ial therapy, the number of prescribed antibiotics, and a recent invasive pro-cedure.In contrast to the present study, they did not identify the effect of different classes of antibiotics on the development of MDR-A. baumannii septicemia.The present study showed exposure to broad spectrum antibiotics

27、, such as carbapenem or beta-lactam/beta-lactamase inhibitor antimicrobials was independently related to MDR-A. baumannii bacteremia.Our findings are similar to a meta-analysis done on the association between exposure to broad spectrum antibiotics and the development of MDR-A. bauman-nii infection (

28、Falagas and Kopterides, 2006b.Exposure to these antibiotics re-sults in the emergence of resistance due to selective pressure and interruption of the colonization resistance mechanism. Previous colonization with A. baumannii was not an independent risk factor in the present study but prior ICU stay

29、was.Us-ing passively collected culture data may underestimate the significance of coloni-zation in our study.Conditions in the ICU provide an environment conducive to the development and maintenance of MDR-A. baumannii.Most patients admitted to the ICU are severely ill, need interventions and freque

30、ntly receive antibiotics, all of which promote multidrug resistant colo-nization and subsequent infection in sus-ceptible patients.The present study may have underestimated the significance of bacterial colonization because of limited surveillance culture data.Therapeutic options are limited for MDR

31、-A. baumannii infection, especially if the isolates are resistant to carbapenem class antibiotics, of which polymyxin or tigecycline may be the only ones available for treatment (Maragakis and Perl, 2008.Variables OR (95%CI Not receiving appropriate empirical antibiotic within 72 hours of bacteremia

32、 3.14 (0.73-13.51 Not receiving appropriate antibiotic during the course of bacteremia 3.71 (0.71-19.32 APACHE II score 1.36 (1.12-1.66 Medical patients 2.42 (0.70-8.40 Drug-resistant A. baumannii 11.92 (2.30-61.83 Secondary bacteremia 7.71 (1.98-29.99 Pneumonia 17.73 (2.09-150.53 Delayed time to re

33、ceipt of appropriate antibiotic (days 0.91 (0.67-1.25 Age 1.05 (1.004-1.09 Factors associated with mortality in patients with MDR A. baumannii bacteremia.Compared to previous studies (Kuo et al, 2007; Lee et al, 2007, the overall mortal-ity rate for A. baumannii bacteremia at our hospital was high:

34、48% in non-MDR A. baumannii infection and > 90% in MDR-A. baumannii.During the study pe-riod, polymyxin and tigecycline were not available at our hospital, which led to a high proportion of patients with MDR-A. baumannii bacteremia not receiving appro-priate antimicrobial therapy resulting in a s

35、ignificantly higher mortality rate than expected.Previous studies have found the administration of ineffective antimi-crobial therapy for carbapenem-resistant A. baumannii bacteremia is a predictor of mortality (Kwon et al, 2007; Jamulitrat et al, 2009.The present study supports the association betw

36、een inappropriate antimicrobial treatment and increasing mortality among patients.Awareness by the physician of risk factors for MDR- A. baumannii infection, available effective antimicrobial agents, and intensive care support may improve clinical outcomes among these patients.Although MDR-A. bauman

37、nii bac-teremia is associated with mortality in the present study as demonstrated on univariate analysis; it was not a major determinant of mortality.The present study showed the independent factors related to death among patients with A. baumannii bacteremia were severity of illness and secondary b

38、acteremia.On multivariate analysis assessing the risk factors for mortality showed increasing trend in mortality in patients contracting MDR- A. baumannii bacteremia, albeit not statistically significant (OR 10.243; 95% CI 0.792-132.513 possibly due to small sample size.The higher mortality rate in

39、patients with MDR- A. baumannii bacteremia may not be directly attributable to drug re-sistance but may be confounded by the effects of underlying disease severity, inappropriate antibiotic treatment and primary source of infection (Jamulitrat et al, 2009.Approximately 40% of patients in the present

40、 study had pneumonia as a primary source of A. baumannii bac-teremia, which is nearly 2 times more common in MDR than in the non-MDR group.Our results support the findings of Agbaht et al (2007 that the bacteremic ventilator-associated pneumonia is more often caused by multidrug-resistant or-ganisms

41、 with a higher risk of death.The present study had limitations. Based on the retrospective study design, some missing data could have resulted in selection bias.Moreover, the small sample size may have affected the power of the study to detect differences.The study de-sign, which used cases with non

42、-MDR-A. baumannii bacteremia as the comparable group, may have overestimated the sig-nificance of antibiotics as a risk factor for contracting MDR-A. baumannii bacteremia (Harris et al, 2002.In conclusion, this study revealed the significant independent factors associated with MDR A. baumannii bacte

43、remia were previous ICU admission and prior use of broad spectrum antibiotics.This infection is associated with a high mortality rate, especially in patients not receiving ap-propriate treatment.Emphasis needs to be placed on prevention, strict application of infection control, and appropriate use o

44、f antibiotics, all of which might reduce the risk and improve the control of this infection.ACKNOWLEDGEMENTSThe authors thank the staff of Sri-nagarind Hospital, Faculty of Medicine, Khon Kaen University, for their care ofthe patients, the Hospital Medical Chart Registration and Clinical Microbiolog

45、ical Laboratory staff for their assistance and Mr Bryan Roderick Hamman and Mrs Janice Loewen Hamman for assistance with the English-language presentation of the manuscript.REFERENCESAgbaht K, Diaz E, Munoz E, et al. Bacteremia in patients with ventilator-associatedpneumonia is associated with incre

46、asedmortality: a study comparing bacteremicvs nonbacteremic ventilator-associatedpneumonia. Crit Care Med 2007; 35: 2064-70. Dijkshoorn L, Nemec A, Seifert H. An increas-ing threat in hospitals: multidrug-resistantAcinetobacter baumannii. Nat Rev Microbiol2007; 5: 939-51.Enoch DA, Summers C, Brown N

47、M, et al.Investigation and management of an out-break of multidrug-carbapenem-resistantAcinetobacter baumannii in Cambridge, UK.J Hosp Infect 2008; 70: 109-18. Falagas ME, Koletsi PK, Bliziotis IA. The di-versity of definition of multidrug-resistant(MDR and pandrug-resistant (PDR Aci-netobacter baum

48、annii and Pseudomonas aeru-ginosa. J Med Microbiol 2006a; 55: 1619-29. Falagas ME, Kopterides P. Risk factors for the isolation of multi-drug-resistant Acineto-bacter baumannii and Pseudomonas aerugi-nosa: a systematic review of the literature.J Hosp Infect 2006b; 64: 7-15. Fournier PE, Richet H. Th

49、e epidemiology and control of Acinetobacter baumannii in healthcare facilities. Clin Infect Dis 2006; 42: 692-9. Gootz TD, Marra A. Acinetobacter baumannii: an emerging multidrug-resistant threat.Expert Rev Anti Infect Ther 2008; 6: 309-25. Harris AD, Samore MH, Lipsitch M, Kaye KS, Perencevich E, C

50、armeli Y. Control-groupselection importance in studies of anti-microbial resistance: examples applied toPseudomonas aeruginosa, Enterococci, andEscherichia coli. Clin Infect Dis2002; 34:1558-63.Jamulitrat S, Arunpan P, Phainuphong P. At-tributable mortality of imipenem-resistantnosocomial Acinetobac

51、ter baumannii blood-stream infection. J Med Assoc Thai 2009;92: 413-9.Kuo LC, Lai CC, Liao CH, et al. Multidrug-resistant Acinetobacter baumannii bacte-raemia: clinical features, antimicrobialtherapy and outcome. Clin Microbiol Infect2007; 13: 196-8.Kwon KT, Oh WS, Song JH, et al. Impact of imi-penem resistance on mortality in patientswith Acinetobacter bacteraemia. J Antimi-crob Chemother 2007; 59: 525-30.Lee NY, Lee HC, Ko NY, et al. Clinical and economic impact of