Short-term effect of the application of selective decontamination of the digestive tract on different body site reservoir ICU patients colonized by multi-resistant Acinetobacter baumannii

C. Agustía, M. Pujola, M. J. Argerichb, J. Ayatsc, M. Badíad, M. A. Domínguezc, X. Corbellaa and J. Arizaa,*

a Infectious Disease Service, b Infection Control Nurse, c Microbiological Service and d Pharmacy Department, Hospital de Bellvitge, C/Feixa Larga s/n, 08907 L’Hospitalet de Llobregat, University of Barcelona, Barcelona, Spain


    Abstract
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The effect of a selective decontamination of the digestive tract (SDD) regimen including polymyxin and tobramycin on several body site reservoirs was compared between a test group and a control group in intensive care unit (ICU) patients with faecal multi-resistant Acinetobacter baumannii colonization. SDD significantly reduced faecal and pharyngeal carriage when compared with the control group at the end of ICU stay (48% versus 91%, P = 0.001, and 38.5% versus 78%, P = 0.01, respectively), but failed to reduce axillary colonization (75% versus 78%, P = 0.6). In addition, the isolation of A. baumannii from new clinical samples was lower in patients with SDD (45.5% versus 81%, P = 0.05). No resistance to polymyxin was observed. We conclude that the digestive tract reservoir of A. baumannii in ICU patients may be decreased by a SDD regimen.


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Hospital outbreaks of Acinetobacter baumannii are on the increase worldwide, particularly in intensive care units (ICUs). The microorganism's spectacular ability to develop antimicrobial resistance is of great concern.1,2 In some hospitals, epidemic infections have become endemic, and investigations have failed to identify a single environmental source of infection, indicating that patients are a potential reservoir.3–5

In 1992, a significant increase in multi-resistant A. baumannii isolates susceptible only to imipenem, sulbactam and colistin was observed in our hospital. In spite of the introduction of an intensive control programme, the outbreak persisted and a new clone of A. baumannii appeared, which was susceptible only to colistin.5

As the digestive tract has been shown to be a major reservoir for infections in an ICU population, a possible useful effect of selective decontamination of the digestive tract (SDD) as an additional tool to help control outbreaks caused by A. baumannii has been suggested.4,6 However, the idea that both the inanimate environment and other concomitant colonized body sites such as the skin may act as additional reservoirs of infection and the extremely narrow therapeutic margin available against many A. baumannii epidemic clones cast doubt on the real efficacy of classical SDD regimens. Thus, before SDD can be considered as an additional measure to control A. baumannii outbreaks in ICU patients, we undertook the present prospective study to determine the effect of applying SDD on several body site reservoirs in ICU patients with multi-resistant A. baumannii colonization.


    Materials and methods
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The study was conducted in the ICU over two different periods in order to avoid the crossover effect on colonization/infection from the group given SDD to the control group. To assess A. baumannii colonization, axillary, pharyngeal and rectal swabs were obtained within 48 h of ICU admission and then weekly until discharge. The control group included all patients admitted from 1 October to 30 November 1998 in whom A. baumannii faecal colonization was detected, and who had at least one series of axillary-pharyngeal-rectal swabs carried out after the detection of faecal colonization. During the second period, from 1 May to 30 June 1999, all patients with A. baumannii faecal colonization who had an expected ICU stay of >5 days were given SDD (a measure approved by the Hospital Infection Committee), and those in whom at least one series of control swabs were obtained after the beginning of SDD were included in the intervention group.

The SDD consisted of a combination of polymyxin E (150 mg), and tobramycin (80 mg), administered in 20 mL liquid form, four times per day, either orally or through a nasogastric tube. In addition, 0.5 g gel containing 2% of each of the above two antimicrobials was applied round the gum margins and oropharynx four times per day, starting on the day of detection of the A. baumannii faecal colonization and maintained until discharge from the ICU.

A. baumannii isolates were identified by the microbiology laboratory using standard biochemical reactions and their ability to grow at 37, 41 and 44°C. Antibiotic susceptibility was assessed by the microdilution method (MicroScan, NegCombo Type 6I plates; Dade International Inc., West Sacramento, CA, USA). Breakpoints for colistin were those defined by the French Society for Microbiology; isolates were considered susceptible to colistin if the MIC was <=2 mg/L.

Statistical analysis

The probability of persistence of axillary, pharyngeal and rectal colonization was calculated in both groups using Kaplan–Meier estimates. A two-tailed P value of <0.05 was considered statistically significant. Statistical analyses were carried out with the SPSS-PC statistical package (SPSS, Chicago, IL, USA).


    Results
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Thirty-three of 167 patients were included as the control group and 21 patients who received SDD (mean 20.3 ± 13.7 days) of 153 patients formed the intervention group. The overall rate of A. baumannii colonization during the control period compared with the intervention period was 56 of 167 (33.5%) versus 55 of 153 (35.9%), respectively. No significant differences regarding demographic characteristics, underlying diseases, length of ICU stay, systemic antibiotic therapies and mortality were observed between groups (Table 1Go).


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Table 1. Characteristics of control group and SDD group patients
 
Concomitant pharyngeal and cutaneous A. baumannii colonization at the time of detection of faecal carriage was observed in 27 patients (82%) in the control group and in 13 (62%) and in 20 patients (95%), respectively, in the SDD group. While rates of faecal, pharyngeal and axillary colonization remained stable during ICU stay in the control group [30 (91%), 21 (78%) and 21 (78%) patients, respectively, upon discharge from ICU], faecal and pharyngeal carriage was significantly reduced after the introduction of SDD [10 (48%), P < 0.001 and five (38%) patients, P = 0.03, respectively]. However, cutaneous carriage of A. baumannii persisted in 15 (75%) patients in the SDD group. By Kaplan–Meier estimations, the probability of persistence of faecal or pharyngeal colonization by the third week of ICU stay was significantly higher in the control group: 92.7% and 81%, respectively, compared with the intervention group: 43.7% (P < 0.001) and 31% (P < 0.001) respectively, whereas the probability of persistence of cutaneous colonization upon discharge was similar in both groups.

The risk of subsequent appearance of clinical colonization or infection by A. baumannii was also evaluated among the 32 patients in whom previous or simultaneous clinical samples positive for multi-resistant A. baumannii had not been detected at the time of faecal carriage: 21 of 33 (63.6%) in the control group and 11 of 21 (52.3%) in the SDD group. The development of new positive clinical samples was higher in the control group when compared with the intervention group, mainly because of the increased number of positive respiratory tract samples; also, the first positive clinical sample appeared later in the SDD group than in the control group (Table 2Go).


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Table 2. Comparison of patients without previous or simultaneous clinical samples at the beginning of the study (at the detection of intestinal colonization)a
 
No differences were observed between the two groups in the incidence of clinical samples positive for other causative organisms, although infection or colonization due to Gram-negative bacilli tended to be less frequent in the SDD group [Gram-positive cocci: 19 of 33 (57.5%) versus 11 of 21 (52.3%) (NS), and Gram-negative bacilli: 21 of 33 (63.6%) versus nine of 21 (42.8%) (NS) in control and SSD groups, respectively].

All A. baumannii strains initially isolated in patients from the SDD group were tobramycin resistant and susceptible to colistin. No resistance to colistin developed during the study.


    Discussion
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
This is a pilot study that evaluated the potential efficacy of SDD in patients with multi-resistant A. baumannii intestinal colonization. While SDD has been used in ICU patients as a control measure for eradicating nosocomial outbreaks due to some multi-resistant Gram-negative bacilli,7,8 no information is available concerning its use in A. baumannii outbreaks.

We used a SDD standard schedule of colistin and tobramycin, despite the fact that our A. baumannii faecal isolates were tobramycin resistant (MICs > 128 mg/L), but no other alternatives were available. The colistin dose we used (600 mg), reported in a previous study,9 was higher than that recommended (400 mg) and had no significant adverse effects.

To avoid a crossover impact,7 the control group of patients was recruited several months before, during a previous study.

The effects of SDD were significant: faecal and pharyngeal decolonization was achieved in more than half of the patients and a decrease and delay in the development of positive clinical samples was observed. In contrast, cutaneous colonization of patients was not affected by the use of SDD, confirming the importance of skin colonization as a natural habitat in the epidemiology of A. baumannii. Accordingly, clinical samples such as catheters and surgical wounds were similarly positive in both SDD patients and controls.

No development of resistance to colistin was detected in strains of A. baumannii isolated in the course of SDD. Reports of a higher number of isolations of Gram-positive microorganisms in patients following SDD have aroused some controversy, but no significant effect on clinical samples in these patients has been demonstrated.10 There were no differences regarding positive clinical samples for Gram-positive organisms in our patients.

In summary, the activity of SDD may be beneficial, decreasing the intestinal reservoir in ICU patients with A. baumannii colonization. The magnitude of the effect will depend on the resistance pattern of the strain involved and probably also on the rates of carriage on other body sites. As no effect on other ecological niches, such as patient skin colonization, was found in our study, it seems advisable that if SDD is used in the setting of an A. baumannii outbreak, decontamination should not be restricted to the digestive tract, but applied also to the skin in order to reduce the risk of persistence of a reservoir and potential recolonization of the gut. Further studies are required to show whether our findings can be replicated in other ICU settings, such as with a shorter length of stay.


    Notes
 
* Corresponding author. Tel: +34-93-2607625; Fax: +34-93-2607637; E-mail: jariza{at}csub.scs.es Back


    References
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
1 . Bergogne-Berezin, E. & Towner, K. J. (1996). Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features. Clinical Microbiology Review 9, 148–65. [ISI]

2 . Go, E. S., Urban, C., Burns, J., Kreiswirth, B., Eisner, W., Mariano, N. et al. (1994). Clinical and molecular epidemiology of Acinetobacter infections sensitive only to polymyxin B and sulbactam. Lancet 344, 1329–32. [ISI][Medline]

3 . Seifert, H., Boullion, B., Schulze, A. & Pulverer, G. (1994). Plasmid DNA profiles of Acinetobacter baumannii: clinical application in a complex endemic setting. Infection Control and Hospital Epidemiology 15, 520–8. [ISI][Medline]

4 . Timsit, J. F., Garrait, V., Misset, B., Goldstein, F. W., Renaud, B. & Carlet, J. (1993). The digestive tract is a major site for Acinetobacter baumannii colonization in intensive care unit patients. Journal of Infectious Diseases 168, 1336–7. [ISI][Medline]

5 . Corbella, X., Montero, A., Pujol, M., Domínguez, M. A., Ayats, J., Argerich, M. J. et al. (2000). Emergence and rapid spread of carbapenem resistance during a large and sustained hospital outbreak by multiresistant Acinetobacter baumannii. Journal of Clinical Microbiology 38, 4086–95. [Abstract/Free Full Text]

6 . Corbella, X., Pujol, M., Ayats, J., Sendra, M., Ardanuy, C., Domínguez, M. A., Liñares, J. et al. (1996). Relevance of digestive tract colonization in the epidemiology of multiresistant Acinetobacter baumannii. Clinical Infectious Diseases 23, 329–34. [ISI][Medline]

7 . Brun-Buisson, C., Legrand, P., Rauss, A., Richard, C., Montravers, F., Besbes, M. et al. (1989). Intestinal decontamination for control of nosocomial multiresistant Gram-negative bacilli. Annals of Internal Medicine 110, 873–81. [ISI][Medline]

8 . Taylor, M. E. & Oppenheim, B. A. (1991). Selective decontamination of the gastrointestinal tract as an infection control measure. Journal of Hospital Infections 17, 271–8. [ISI][Medline]

9 . Van Saene, J. J. M., Van Saene, H. K. F., Tarko-Smit, N. J. Ph. & Beukeveld, G. J. J. (1988). Enterobacteriaceae supression by three different oral doses of polymixin E in human volunteers. Epidemiology and Infection 100, 407–17. [ISI][Medline]

10 . Hammond, J. M. J. & Potgieter, P. D. (1995). Long-term effects of selective decontamination on antimicrobial resistance. Critical Care Medicine 23, 637–45. [ISI][Medline]

Received 5 February 2001; returned 13 June 2001; revised 24 August 2001; accepted 27 September 2001