x

¿Aún no está registrado?

Cree su cuenta. Regístrese en Elsevier y obtendrá: información relevante, máxima actualización y promociones exclusivas.

Registrarme ahora
Help - - Sign up - Phone number 902 888 740
Search

2013 FI

1.252
© Thomson Reuters, Journal Citation Reports, 2013

Indexed in:

Current Contents/Clinical Medicine, Journal Citation Reports, SCI-Expanded, Index Medicus/Medline, Excerpta Medica/EMBASE, IBECS, IME, MEDES, PASCAL, SCOPUS, SciVerse ScienceDirect

SCImago Index

SCImago Journal & Country Rank
doi: 10.1016/j.medcli.2011.06.024

Multidrug and carbapenem-resistant Acinetobacter baumannii infections, Factors associated with mortality

Infecciones por Acinetobacter baumannnii multirresistente y resistente a carbapenem, factores asociados a la mortalidad

Alicia Hernández-Torres a, , Elisa García-Vázquez ab, Joaquín Gómez ab, Manuel Canteras c, Joaquín Ruiz d, Genoveva Yagüe d

a Services of Internal Medicine-Infectious Diseases, University Hospital Virgen de la Arrixaca, Spain
b Department of Internal Medicine, Faculty of Medicine, University of Murcia, Murcia, Spain
c Department of Biostatistics, Faculty of Medicine, University of Murcia, Murcia, Spain
d Microbiology Service, University Hospital Virgen de la Arrixaca, Spain

Keywords

Acinetobacter baumannii. Multidrug resistant. Infection. Mortality. Treatment.

Palabras Clave

Acinetobacter baumannii. multiresistente. infección. mortalidad. tratamiento.

Abstract

Background and objective

To analyse factors related to mortality and influence of antibiotic treatment on outcome in patients with nosocomial infection due to multidrug and carbapenem-resistant Acinetobacter baumannii (MDR-C AB).

Patients and methods

Observational and prospective study of a cohort of adult patients with MDR-C AB infection. Data collection from clinical records was done according to a standard protocol (January 2007 through June 2008). Patients with MDR-C AB infection were identified by review of results of microbiology cultures from the hospital microbiology laboratory. Epidemiological and clinical variables and predictors of mortality were analysed.

Results

24 out of 101 cases were considered colonizations and 77 infections (27 bacteraemia); global mortality in infected patients was 49% (18 cases with bacteraemia and 20 with no bacteraemia). In the multivariate analysis, including the 77 cases of infection, the prognosis factors associated with mortality were age (OR 1.09; 95% CI 1.02–1.2), McCabe 1 (OR 33.98; 95% CI 4.33–266.85), bacteraemia (OR 9.89; 95% CI 1.13–86.13), inadequate empiric treatment (OR 16.7; 95% CI 2.15–129.79), and inadequate definitive treatment (OR 26.29; 95% CI 1.45–478.19). In the multivariate analysis including the 57 cases of infection with adequate definitive treatment, the prognosis factors associated with mortality were McCabe 1 (OR 24.08; 95% CI 3.67–157.96) and monotherapy versus combined treatment (OR 7.11; 95% CI 1.63–30.99).

Conclusions

Our cohort of patients with MDR-C AB infection is characterised by a very high mortality (49%); the severity of patients and inadequate treatment or monotherapy are statistically associated with mortality.

Resumen

Fundamento y objetivo

Analizar los factores asociados a mortalidad y la influencia del tratamiento antibiótico en la evolución de los pacientes con infección por Acinetobacter baumannii multiresistente y resistente a carbapenem (ABMDR-C).

Pacientes y métodos

Estudio observacional y prospectivo de una cohorte de pacientes adultos con infección por ABMDR-C (Enero 2007 a junio 2008). Los casos de infección se identificaron a partir de los resultados de los cultivos microbiológicos. Analizamos las variables epidemiológicas y clínicas asociadas a mortalidad.

Resultados

Veinticuatro de los 101 aislamientos de ABMDR-C se consideraron colonizaciones y 77 fueron definidos como infecciones (27 bacteriemias); la mortalidad global de los casos de infección fue del 49% (18 pacientes con bacteriemia y 20 sin bacteriemia). En el análisis multivariado que incluía a los 77 pacientes con infección, los factores predictores de mortalidad fueron: edad (OR 1,09; IC95% 1,02-1,2), McCabe 1 (OR 33,98; IC95% 4,33-266,85), bacteriemia (OR 9,89; IC95% 1,13-86,13), tratamiento empírico inadecuado (OR 16,7; IC95% 2,15-129,79), tratamiento definitivo inadecuado(OR 26,29; IC95% 1,45-478,19). En el análisis multivariado que incluía los 57 pacientes que recibieron tratamiento definitivo adecuado, los factores predictores de mortalidad fueron McCabe 1 (OR 24,08; IC95% 3,67-157,96) y tratamiento en monoterapia versus combinaciones (OR 7,11; IC95% 1,63-30,99).

Conclusiones

En nuestra cohorte de pacientes con infección por ABMDR-C la mortalidad es elevada (49%); los pacientes graves y el tratamiento antibiótico inadecuado o el tratamiento definitivo adecuado en monoterapia se asocian de forma estadísticamente significativa a mayor mortalidad.

Article

Introduction

The clinical impact of severe infections due to multidrug and carbapenem-resistant Acinetobacter baumannii (MDR-C AB) is extensively discussed in the medical literature, since results and conclusions are contradictory, probably due to differences in methodology, pathogenicity and virulence of the isolated strains within different geographical areas.1, 2, 3

There is also controversy about the influence of MDR-C AB on mortality,2, 4 as well as to the positive effect of the adequate antibiotic treatment on prognosis.5

Faced with these discrepancies, we carried out a prospective analysis of a cohort of patients with MDR-C AB infection, to evaluate the prognostic factors associated with mortality and the influence of adequate treatment.

Patients and method

We carried out a prospective and observational study of all documented nosocomial infections due to MDR-C A. baumannii corresponding to adult patients admitted to Hospital Universitario Virgen de la Arrixaca in the period comprised between January 2007 and June 2008. Information about patients was collected according to a previously established protocol. Patients admitted to either the paediatrics or the maternal units were excluded as they corresponded to polymicrobial isolates. This cohort has partially been analysed in a previous publication.6

Microbiological study

The blood cultures were processed using the BACT-ALERT system (Becton-Dickinson, Sparks, MD). The samples from other locations were processed by the Service of Microbiology following the standard procedure and by means of the usual microbiological techniques.

The identification and study of antimicrobial susceptibility of the isolated microorganisms were conducted by means of the automated Vitek-2 system (Biomerieux, Lyon, France), using the ID-GN and AST-N059 cards. The activity of tygecycline, tobramycin and amikacin was checked by means of the E-test (AB Biodisk, Solna, Sweeden). Multiresistance associated with carbapenem-resistance was defined as the presence of in vitro resistance to imipenem (CMI≥16μg/ml) and with more than four of the following antibiotics: piperacillin-tazobactam, aztreonam, ciprofloxacin, ceftazidime, ampicillin-sulbactam and tobramycin or amikacin. Molecular studies were not performed.

Patients

Patients were assessed with regard to the prognosis of their underlying disease, according to the criteria of McCabe and Jackson.7 Their condition was then classified as “rapidly fatal” when death was expected to take place in days or weeks, “ultimately fatal” when death was likely to take place in some months or years, and “nonfatal” when death was not predictable. The severity of the patient's condition at presentation was assessed according to Winston et al.,8 as follows: “critical” when the patient's clinical condition was rapidly deteriorating and the probability of death during the first 24h was high; “poor” when the clinical condition was deteriorating and death was probable but not imminent; “fair” when the clinical condition was deteriorating but death was not probable; and “good” when the clinical situation did not change during the first 24h and death was not probable.

Infection study

The epidemiological characteristics of patients with documented nosocomial infection were assessed. Only samples collected after 72h of hospital admission or within the first 72h after admission in the case of antecedent of admission in the previous month were included. The patients were divided into 2 groups: patients with colonization of MDR-C AB (group A) and patients with documented infection (group B), who were subdivided into two groups, patients with bacteraemia (group B1) and patients without bacteraemia (group B2). The sources and types of infection were determined in accordance with Atlanta's CDC criteria.9 The study of the prognostic factors related to mortality was carried out with the infected patients, excluding the cases of colonization.

Colonization was defined as the presence of A. baumannii in a non-sterile sample in a patient without symptoms or signs of infection.

Prognostic factors

In order to identify prognostic factors, all clinical and epidemiological characteristics, all complications, and the type of antibiotic treatment were examined in relation to the final evolution of patients, with “recovery” understood to be the disappearance of all active signs and symptoms of infection. Patients with poor prognosis were divided in 3 subgroups based on the time of death; in the first subgroup, death occurred within the first 3 days after the documentation of infection; in the second subgroup death occurred between the 4th and 7th day; and in the third group death occurred after the 8th day following the documentation of infection. Patients were followed up until death or discharge.

Type of treatment

Empiric treatment was defined as the antibiotics prescribed by the physician who assessed a patient with clinical symptoms of infection when the microbiological samples were obtained. Definitive treatment was defined as the antibiotics prescribed according to the microbiological information (A. baumannii isolation and susceptibility pattern).

The empirical treatment was considered to be inadequate when the patient did not receive any in vitro active antibiotic in the adequate doses. Definite treatment was considered to be inadequate when the patient did not receive in the adequate doses any of the in vitro active antimicrobials against A. baumannii, at least during a whole day.

Likewise, definite treatment was classified into monotherapy and combined treatment, considering as combinations those specified in Table 1.

Table 1. Definite treatment.

Type of antibiotic treatment Patients (n=77) N (%) Mortality (n=38) N (%)
Monotherapy 33 (43) 21 (55)
Tigecycline 11 (14) 9 (24)
Sulbactam 6 (8) 4 (10)
Amikacin 8 (10) 3 (8)
Tobramycin 4 (5) 3 (8)
Colistin 4 (5) 2 (5)
 
Combinations 37 (48) 10 (26)
Tigecycline+rifampicin±amikacin 9 (12) 3 (8)
Sulbactam+amikacin 8 (10) 2 (5)
Colistin+rifampicin 1 (1) 0 (0)
Tigecycline+colistin+rifampicin 19 (25) 5 (13)
 
Without treatment 7 (9) 7 (18)
Statistical analysis

Data were analysed using the statistics program SPSS 15.0 (SPSS Software, Chicago, IL, USA). The relation or association between pairs of qualitative variables was determined through analyses of contingency tables by means of Pearson's χ2-test, complemented by an analysis of residues with the aim of determining the directional dependence. In the case of quantitative variables, means were compared using Student's t-test. The difference was considered significant at p<0.05. A multivariate analysis was carried out in order to detect the predictors of global mortality in patients with infection due to MDRAB-C; this analysis consisted of a non-conditional logistic regression in which death was considered as a dependent variable and all those that had been statistically associated with mortality in the bivariate analysis were included as independent variables.

Results

Out of 101 patients with A. baumannii isolation, 24 were excluded because they were considered as cases of colonization (group A) and 77 were considered to have developed an infection (group B) (27 cases of bacteraemia – group B1 – and 50 non-bacteraemic infections – group B2); all cause mortality in both groups of patients (A and B) was of 41.6% (4 patients in group A and 38 in group B – 18 in group B1). From here on we will present a description and analysis of the cohort 77 infected patients.

Early mortality (first 72h after the microbiological isolation) was 10.39% in group B (14.8% in group B1 and 8% in group B2) (Table 2).

Table 2. Comparative study of bacteremic and non-bacteremic infections.

Characteristics Total cohortn=77N (%) Bacteremic infectionn=27N (%) Non-bacteremic infectionn=50N (%) p
AGE (years) 55 49 59 ns
 
Sex
Men 56 (73) 19 (70) 37 (74) ns
Women 21 (27) 8 (30) 13 (26)  
 
Comorbidities
Yes 59 (77) 19 (70) 40 (80) ns
Diabetes mellitus 24 (31) 3 (11) 21 (42) <0.05
Arterial hypertension 37 (48) 9 (33) 28 (56) ns
Alcoholism 10 (13) 5 (18) 5 (10) ns
Smoking 18 (23) 6 (22) 12 (24) ns
Dyslipidemia 10 (13) 2 (7) 8 (16) ns
Lung disease 16 (21) 3 (11) 13 (26) ns
Kidney failure 11 (14) 2 (7) 9 (18) ns
Liver disease 9 (12) 4 (15) 5 (10) ns
Heart disease 30 (39) 10 (37) 20 (40) ns
Vasculopathy 9 (12) 3 (11) 6 (12) ns
Immunosuppression 14 (18) 7 (26) 7 (14) ns
Trasplantation 11 (14) 6 (22) 5 (10) ns
Systemic disease 4 (5) 1 (4) 3 (6) ns
Cancer 10 (13) 2 (7) 8 (16) ns
 
McCABE
1 28 (36) 14 (52) 14 (28) <0.05
2 24 (31) 9 (33) 15 (30)  
3 25 (32) 4 (15) 21 (42)  
 
Admission service
Medical 12 (16) 1 (4) 11 (22) <0.05
Surgical 65 (84) 26 (96) 39 (78)  
 
ICU admission 64 (83) 27 (100) 37 (74) <0.05
Invasive procedures 69 (90) 27 (100) 42 (84) ns
Mechanical ventilation 59 (77) 25 (93) 34 (68) <0.05
Tracheotomy 45 (58) 18 (67) 27 (54) ns
Central venous catheter 64 (83) 27 (100) 37 (74) <0.05
Nasogastric tube 52 (67) 20 (74) 32 (64) ns
Enteral nutrition 37 (48) 14 (52) 23 (46) ns
Parenteral nutrition 44 (57) 20 (74) 24 (48) <0.05
Red blood cells transfusions 64 (83) 26 (96) 38 (76) <0.05
Urinary catheter 66 (86) 26 (96) 40 (80) ns
Surgery 65 (84) 27 (100) 38 (76) <0.05
Previous antibiotics 16 (21) 5 (18) 11 (22) ns
 
Winston 61 (79) 22 (81) 39 (78)  
≤2 52 (67) 22 (81) 30 (60) ns
>2 25 (32) 5 (18) 20 (40)  
 
Leukocytosis
<12,000cells/mm3 33 (43) 14 (52) 19 (38) ns
>12,000cells/mm3 44 (57) 13 (48) 31 (62)  
 
Hemoglobin
<10g/dl 63 (82) 25 (93) 38 (76) ns
>10g/dl 14 (18) 2 (7) 12 (24)  
 
Complications 36 (47) 17 (63) 19 (38) ns
Kidney failure 21 (27) 10 (37) 11 (22) ns
Acute respiratory distress syndrome 23 (30) 12 (44) 11(22) <0.05
Hepatic failure 9 (12) 6 (22) 3 (6) <0.05
Shock 25 (32) 12 (44) 13 (26) ns
 
Exitus vitae 38 (49) 18 (67) 20 (40) <0.05
Within the first 3 days 8 (10) 4 (15) 4 (8)  
Between 4th and 7th day 4 (5) 1 (4) 3 (6)  
After the 7th day 26 (34) 13 (48) 13 (26)  

When comparing group B1 and B2 statistically significant differences were found in the mortality rate, the proportion of patients with rapidly fatal underlying diseases, diabetes mellitus incidence, the rate of surgical and ICU-patients, some of the invasive procedures that the patients underwent and in the number of complications (acute respiratory distress syndrome and liver failure) (Table 2). Susceptibility data of the isolates are shown in Table 3.

Table 3. A. baumannii: susceptibility patterns (N=77).

Antibiotics SN (%) IN (%) RN (%) No informationN (%)
Piperacillin-tazobactam 0 0 77 (100) 0
Aztreonam 0 0 77 (100) 0
Cephalosporins 0 0 77 (100) 0
Carbapenems 0 0 77 (100) 0
Quinolones 0 0 77 (100) 0
 
Aminoglycosides
Amikacin 44 (57) 8 (10) 10 (13) 15 (19)
Tobramycin 44 (57) 6 (8) 24 (31) 3 (4)
Gentamicin 23 (30) 2 (3) 44 (57) 8 (10)
 
Sulbactam 23 (30) 29 (38) 16 (21) 9 (12)
Colistin 77 (100) 0 0 0
Tigecycline 54 (70) 9 (12) 1 (1) 13 (17)

Mortality according to antibiotic treatment can be seen in Table 1. As for the prognosis of the patients with infections due to MDR-C AB, in the bivariant analysis a statistically significant relation was found between mortality and presence of underlying conditions, McCabe 1, heart disease, Winston≤2, as well as the presence of bacteraemia, anaemia (hemoglobin<10mg/dl) and the development of complications such as kidney failure, acute respiratory distress syndrome and shock (Table 4). Inadequate antibiotic treatment, both empirical and definite ones, and the use of monotherapy versus combined definitive treatment, were significantly associated with a higher mortality (Table 4). Seven patients did not receive antibiotic treatment due to early death before microbiological data were available or because the physician in charge did not consider the possibility of an infection.

Table 4. Prognostic factors of patients with A. baumannii infections. Bivariant analysis.

Characteristics Recoveryn=39 (%) Exitusn=38 (%) p
Age years (range) 50 (18–83) 60 (21–88) ns
 
Sex      
Men 30 (77) 26 (68) ns
Women 9 (23) 12 (32)  
 
Comorbilities
Yes 23 (59) 36 (95) <0.05
Diabetes mellitus 12 (31) 12 (32) ns
Arterial hypertension 15 (39) 22 (58) ns
Alcoholism 3 (8) 7 (18) ns
Smoking 6 (15) 12 (32) ns
Dyslipidemia 4 (10) 6 (16) ns
Lung disease 8 (20) 8 (21) ns
Kidney failure 6 (15) 5 (13) ns
Liver disease 3 (8) 6 (16) ns
Heart disease 9 (23) 21 (55) <0.05
Vasculopathy 4 (10) 5 (13) ns
Immunosuppression 3 (8) 11 (29) ns
Trasplantation 3 (8) 8 (21) ns
Systemic disease 1 (3) 3 (8) ns
Cancer 3 (8) 7 (18) ns
 
McCABE
1 2 (5) 26(68) <0.05
2 13 (33) 11 (29)  
3 24 (61) 1 (3)  
 
Admission service
Medical 6 (15) 6 (16) ns
Surgical 33 (85) 32 (84)  
 
ICU admission 30 (77) 34 (90)  
Medical ICU 19 (49) 21 (55) ns
Surgical ICU 11 (28) 13 (34)  
 
Invasive procedures 34 (87) 35 (92) ns
Mechanical ventilation 26 (67) 33 (87) ns
 
Tracheotomy 22 (56) 23 (60) ns
Central venous catheter 30 (77) 34 (90) ns
Nasogastric tube 24 (61) 28 (74) ns
 
Enteral nutrition 19 (49) 18 (47) ns
Parenteral nutrition 19 (49) 25 (66) ns
Red blood cells trasfusions 30 (77) 34 (90) ns
Urinary catheter 31 (79) 35 (92) ns
Surgery 30 (77) 35 (92) ns
Previous antibiotics 29 (74) 32 (84) ns
 
Winston
2 17 (44) 35 (92) <0.05
>2 22 (56) 3 (8)  
 
Leukocytosis
<12,000cells/mm3 17 (44) 16 (42) ns
>12,000cells/mm3 22 (56) 22 (58)  
 
Hemoglobin
<10mg/dl 28 (72) 35 (92) <0.05
>10mg/dl 11 (28) 3 (8)  
 
Isolations
Respiratory 21 (54) 26 (68) ns
Blood culture 9 (23) 18 (47) <0.05
Skin and soft tissue (surgical wounds) 18 (46) 16 (42) ns
Intra-abdominal fluids 3 (8) 2 (5) ns
Urine 5 (13) 3 (8) ns
Central venous catheter tip 10 (26) 12 (32) ns
Central nervous system catheter tip 1 (3) 0 (0) ns
 
Complications
Yes 8 (20) 28 (74) <0.05
Kidney failure 5 (13) 16 (42) <0.05
Acute respiratory distress syndrome 2 (5) 21 (55) <0.05
Hepatic failure 2 (5) 7 (18) ns
Shock 3 (8) 22 (58) <0.05
Empiric treatment:
- Adequate 22 (56) 13 (34) <0.05
- Inadequate 17 (44) 25 (66)  
Definite treatment:
- Adequate 37 (95) 20 (53) <0.05
* Monotherapy 10 (26) 13 (34)  
* Combined treatment 27 (69) 7 (18)  
- Inadequate 2 (5) 18 (47)  

In the multivariant analysis including the 77 cases of infection, the prognosis factors associated with mortality were age (OR 1.09; 95% CI 1.02–1.2), McCabe 1 (OR 33.98; 95% CI 4.33–266.85), bacteraemia (OR 9.89; 95% CI 1.13–86.13), inadequate empiric treatment (OR 16.7; 95% CI 2.15–129.79), and inadequate definitive treatment (OR 26.29; 95% CI 1.45–478.19).

In the multivariate analysis including the 57 cases of infection with adequate definitive treatment, the prognosis factors associated with mortality were McCabe 1 (OR 24.08; 95% CI 3.67–157.96) and monotherapy versus combined treatment (OR 7.11; 95% CI 1.63–30.99).

Discussion

In our cohort of patients with infection due to MDR-C AB, the mortality rate was 49%. When comparing our series of patients with bacteraemia due to MDR-C AB with a historical cohort of patients10 with bacteraemia due to A. baumannii carbapenem-susceptible (ABCS), the former presented a higher mortality (66.7%) than the latter (25.6%). In previous studies5, 11, 12, 13, 14 global mortality ranged from 17% to 62%, depending on differences in the type of patients, the prognosis of the underlying diseases or the initial clinical severity within different cohorts. These mortality rates are similar to ours (49.3%), though early mortality (10.39%) in our series was lower than that noticed by other authors3 (19–35%). This difference could be related to the fact that in our sample both patients with and without bacteraemia were included, while in other studies only cases of bacteraemia were selected (and bacteraemia is in our cohort a factor associated with mortality). The question “is mortality related to MDR-C AB or due to underlying conditions?” remains difficult to answer. In our series, McCabe 1 was a prognostic factor of mortality; however, the fact that the bacteraemia, inadequate empiric or definite treatment are associated with mortality in the multivariate analysis leads us to think that the presence of infection with MDR-C AB also plays a role in the clinical evolution of the patient. These results are similar to those pointed out by other authors. Thus, Cisneros and Rodríguez-Baño15 also found disseminated intravascular coagulation and inadequate antibiotic treatment as factors associated with death. However, other authors have not found an association between inadequate antibiotic treatment and mortality.5, 14, 15 The fact that in some studies inadequate treatment is a factor associated with mortality, while in others only the variables related to severity at onset and those of the underlying conditions are associated with death, prevents from universally accepting that infection with MDR-C AB is per se a mortality factor. Therefore, severity of all underlying conditions would itself determine the critical situation of the patients, in whom infection with MDR-C AB would not be more than an epiphenomenon in a very complex clinical condition.

Unfortunately, we could not carry out in our study, a multivariate study, comparing the historical cohort10 (ABCS) with the group of patients with infections due to MDR-C AB. This represents a restriction which has not allowed us to assess the influence of resistance to carbapenems in the clinical evolution of the patients. If we look through the literature, there are few papers that analyse this aspect, but the results are equally contradictory, since in some cohorts4 the influence of carbapenem resistance in mortality is obvious while in others,13 this variable does not affect patients’ clinical evolution.

There are still not enough data in the literature about which is the most adequate antibiotic treatment in patients with infections due to MDR-C AB. In our series, combined treatment was associated with a lower mortality than monotherapy, both in the bivariant and the multivariant analyses. Research on in vitro synergy,16, 17, 18 some experimental studies19, 20, 21 and some small clinical cohorts,22, 23, 24 also seem to support the idea of prescription of combined treatment against monotherapy, just as probably common sense or knowledge about other multiresistant serious infections recommend. Our clinical experience and this paper, in spite of its limitations, make us think, together with other authors25 that monotherapy is not the best treatment option; in fact, resistance and therefore therapeutic failure have been described during tigecycline treatment.26, 27, 28 We have also appreciated this phenomenon: in two patients with bacteraemia secondary to lung infection and treated with tigecycline, initial MIC was 1mcg/ml and after three days of treatment (and no clinical response) blood cultures remained positive and MIC had gone up to 8mcg/ml; both patients died. Likewise, the appearance of subpopulations of A. baumannii developing resistance during colistin treatment has been described29; the effectiveness of this antibiotic in monotherapy in ventilator-associated pneumonia and severe infections due to MDR-C AB30, 31 ranges between 52% and 61%, being side effects a main disadvantage (mainly nephrotoxicity).32 Sulbactam use, another recommended option in MDR-C AB infections, is limited by the increasing number of resistant strains (more than 50% of the isolates31; 68% in our cohort). Nevertheless, experts recommend the use of sulbactam high doses to overcome this limitation (dose-related side effects are uncommon).

As for combined treatment, in vitro studies and research on experimental20, 21, 22, 23, 24 models have found that the addition of rifampicine to another active antibiotic, such as tigecycline, colistin or sulbactam, has a synergistic effect and limits the development of resistances during treatment; however, studies are controversial and in another experimental work colistin activity was lessened by rifampicine.29 In 26 cases of MDR-C AB severe infections Motaouakkil et al.22 observed an effectiveness of 100% with the combination of colistin and rifampicine and in a cohort of 29 patients treated with high doses of rifampicine (10mg/kg/day) and colistin, Bassetti et al.23 achieved an effectiveness of 76% and only 10% developed nephrotoxicity, despite the fact that patients suffered from previous kidney failure. With the same combination, Petrosillo et al.24 obtained 50% positive results, although they used lower rifampicine doses. We used a standard dose of 600mg/day.

Nowadays, according to some experts, a triple combination of colistin, tigecycline and rifampicine could probably be the choice, though there is not enough clinical experience.

Some of the limitations of our study are (1) small sample size; (2) identification of A. baumannii did not include molecular techniques and (3) we used a Winston score to assess severity, as this is a subjective measure of gravity.

To sum up, the role of MDR-C AB as an infectious agent in the prognosis of severely compromised patients is not clarified and more studies looking deeply into the true clinical impact of resistance are needed. However, meanwhile, better epidemiological knowledge and the establishment and adequate fulfilment of nosocomial infection control programs and antibiotics’ prescription policies (mainly carbapenems) might contribute to reduce the incidence of MDR-C AB infections, as well as achieve a more adequate clinical and therapeutic approach.33

Conflicts of interest

The authors have no relevant financial interest in this article or financial conflicts of interest. None to declare.

Received 24 March 2011
Accepted 30 June 2011

Corresponding author. elisag@eresmas.net

Bibliography

1.Sunenshine RH, Wright MO, Maragakis LL, Harris AD, Song X, Hebden J, et al. Multidrug-resistant Acinetobacter infection mortality rate and length of hospitalization. Emerg Infect Dis. 2007; 13:97-103.
Medline
2.Falagas ME, Kopterides P, Siempos II. Attributable mortality of Acinetobacter baumannii infection among critically ill patients. Clin Infect Dis. 2006; 43:389-90.
Medline
3.Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev. 2008; 21:538-82.
Medline
4.Gkrania-Klotsas E, Hershow RC. Colonization or infection with multidrug-resistant Acinetobacter baumannii may be an independent risk factor for increased mortality. Clin Infect Dis. 2006; 43:1224-5.
Medline
5.Chen HP, Chen TL, Lai ChH , Fung CP, Wong WW, Yu KW, et al. Predictors of mortality in Acinetobacter baumannii bacteremia. J Microbiol Immunol Infect. 2005; 38:127-36.
Medline
6.Hernández-Torres A, García-Vázquez E, Gómez J, Canteras M, Ruiz J, Fernández-Rufete A, et al. Carbapenem and multidrug resistant A. baumannii colonisation/infection: epidemiology and factors associated with infection. Med Clin. 2010; 135:389-96.
7.McCabe WR. Endotoxin and bacteremia due to gram-negative organisms. N Engl J Med. 1970; 283:1342-3.
Medline
8.Winston DJ, Murphy W, Young LS, Hewitt WL. Piperacillin therapy for serious bacterial infections. Am J Med. 1980; 69:255-61.
Medline
9.Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections. Am J Infect Control. 1988; 16:128-40.
Medline
10.Gómez J, Simarro E, Baños V, Requena L, Ruiz J, García , Canteras M, Valdés M. Six-year prospective study of risk and prognostic factors in patients with nosocomial sepsis caused by Acinetobacter baumannii. Eur J Clin Microbiol Infect Dis. 1999; 18:358-61.
Medline
11.Warcham DW, Bean DC, Khanna P, Hennesy EM, Krahe D, Ely A, et al. Bloodstream infection due to Acinetobacter spp: epidemiology, risk factors and impact of multi-drug resistance. Eur J Clin Microbiol Infect Dis. 2008; 27:607-12.
Medline
12.Kwon KT, Oh WS, Song JH, Chang HH, Jung SI, Kim SW, et al. Impact of imipenem resistance on mortality in patients with Acinetobacter bacteraemia. J Antimicrob Chemother. 2007; 59:525-30.
Medline
13.Tseng YCh , Wang JT, Wu FL, Chen YCh , Chie WCh , Chang SCh. Prognosis of adult patients with bacteremia caused by extensively resistant Acinetobacter baumannii. Diagn Microbiol Infect Dis. 2007; 59:181-90.
Medline
14.Seifert H, Strate A, Pulverer G. Nosocomial bacteraemia due to Acinetobacter baumannii: clinical features, epidemiology, and predictors of mortality. Medicine (Baltimore). 1995; 74:340-9.
15.Cisneros JM, Rodríguez-Baño J. Nosocomial bacteremia due to Acinetobacter baumannii: epidemiology, clinical features and treatment. Clin Microbiol Infect. 2002; 8:687-93.
Medline
16.Dizbay M, Altuncekic A, Sezer BE, Ozdemir K, Arman D. Colistin and tigecycline susceptibility among multidrug-resistant Acinetobacter baumannii isolated from ventilator-associated pneumonia. Int J Antimicrob Agents. 2008; 32:29-32.
Medline
17.Tripodi MF, Durante-Mangoni E, Fortunato R, Utili R, Zarrilli R. Comparative activities of colistin, rifampicin, imipenem, and sulbactam/ampicillin alone or in combination against epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemases. Int J Antimicrob Agents. 2007; 30:537-40.
Medline
18.Song JY, Kee SY, Hwang IS, Seo YB, Jeong HW, Kim WJ, et al. In vitro activities of carbapenem/sulbactam combination, colistin, colistin/rifampicin combination and tigecycline against carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother. 2007; 60:317-22.
Medline
19.Lee ChH , Tang YF, Su LH, Chien ChCh , Liu JW. Antimicrobial effects of varied combinations of meropenem, sulbactam, and colistin on a multidrug-resistant Acinetobacter baumannii isolate that cause meningitis and bacteremia. Microb Drug Resist. 2008; 14:233-7.
Medline
20.Song JY, Cheong HJ, Lee J, Sung AK, Kim WJ. Efficacy of monotherapy and combined therapy for carbapenem-resistant Acinetobacter baumannii pneumonia in an immunosuppressed mouse model. Int J Antimicrob Agents. 2009; 33:33-9.
Medline
21.Pachón-Ibañez ME, Fernández-Cuenca E, Docobo-Pérez E, Pachón J, Pascual A. Prevention of rifampicin resistance in Acinetobacter baumannii in an experimental pneumonia murine model, using rifampicin associated with imipenem or sulbactam. J Antimicrob Chemother. 2006; 58:689-92.
Medline
22.Motaouakkil S, Charra B, Hachimi A, Nejmi H, Benslama A, Elmdaghri F, et al. Colistin and rifampicin in the treatment of nosocomial infections from multiresistant Acinetobacter baumannii. J Infect. 2006; 53:274-8.
Medline
23.Bassetti M, Repetto E, Righi E, Boni S, Diverio M, Molinari MP, et al. Colistin and rifampicin in the treatment of multidrug-resistant Acinetobacter baumannii infections. J Antimicrob Chemother. 2008; 61:417-20.
Medline
24.Petrosillo N, Ioannidou E, Falagas ME. Colistin monotherapy vs. combination therapy: evidence from microbiological, animal, and clinical studies. Clin Microbiol Infect. 2008; 14:816-27.
Medline
25.Pachón J, Vila J. Treatment of multiresistant Acinetobacetr baumannii infections. Curr Opin Investig Drugs. 2009; 10:150-6.
Medline
26.Gordon NC, Wareham DW. A review of clinical and microbiological outcomes following treatment of infections involving multidrug-resistant Acinetobacter baumannii with tigecycline. J Antimicrob Chemother. 2009; 63:775-80.
Medline
27.Gallagher JC, Rouse HM. Tigecycline for the treatment of Acinetobacter infections: a case series. Ann Pharmacother. 2008; 42:1188-94.
Medline
28.Vila J, Pachón J. Therapeutic options for Acinetobacter baumannii infections. Expert Opin Pharmacother. 2008; 9:587-99.
Medline
29.Li J, Rayner CR, Nation RL, Owen RJ, Spelman D, Tan KE, et al. Heteroresistance to colistin in multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2006; 50:2946-50.
Medline
30.Oliveira MS, Prado GV, Costa SF, Grinbaum RS, Levin AS. Ampicillin/sulbactam compared with polymixins for the treatment of infections caused by carbapenem-resistant Acinetobacter spp. J Antimicrob Chemother. 2008; 61:1369-75.
Medline
31.Betrosian AP, Farntzeskaki F, Xanthaki A, Douzinas EE. Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia. J Infect. 2008; 56:432-6.
Medline
32.Gounden R, Bamford C, Zyl-Smit RV, Cohen K, Maartens G. Safety and effectiveness of colistin compared with tobramycin for multi-drug resistant Acinetobacter baumannii infections. BMC Infect Dis. 2009; 9:1-8.
Medline
33.Catalán M, Aguado JM. Multiresistant A. baumannii: an universal challenge. Med Clin. 2010; 135:406-7.