Journal

of Hospital

(1992) 20, 199-208

Infection

Epidemiology intensive care

of Pseudomonas aeruginosa in an unit using selective decontamination of th.e digestive tract

P. J. Armstrong*, *Department

of Surgery, Bacteriology,

J. G., Bars-T, C. H. Webb?, P. Y. Blair* B. J. Rowlands’

and

The Queen’s University, Belfast and TDepartment Royal Victoria Hospital, Belfast, UK

Accepted for publication

of

16 December 1991

Summary:

Selective decontamination of the digestive tract (SDD) aims to reduce the rate of nosocomial infections in critical care patients. Pseudomonas spp. are common nosocomkl pathogens and in this study isolates collected from patients and the environment during an SDD trial were examined. The study enrolled 161 SDD cases and 170 controls. Pseudomonads were isolated from 27% of SDD patients and 30% of controls. SDD partially suppressed colonization in the ‘gastro-respiratory’ mucosae but not in the rectum. A total of 108 isolates of pseudomonads were recovered from the environment. Resistance in rectal isolates was minimal but isolates from ‘gastro-respiratory’ sites showed increasing aminoglycoside resistance. Eighty-six per cent of aminoglycoside-resistant isolates from both patient groups and environment were pyocine type lx. Episodes of infection were reduced in the SDD patients (6) compared with the controls (16), aminoglycoside-resistant strains being associated with zero (episodes in SDD patients but with five in the control group. Keywords:

Selective

decontamination;

Pseudomonas

aeruginosa;

pyocine

type.

Introduction

A majority of patients in intensive care units acquire infections which are often endogenous in origin. These patients are most susceptible to infection by facultative Gram-negative bacilli. Selective decontamination of the digestive tract (SDD) aims to reduce these infections by selectively eliminating the potentially pathogenic organisms from the gut leaving the indigenous flora intact. 1,2 Pseudomonas spp. are often the Gram-negative bacteria associated with infection; Pseudomonas aeruginosa is most commonly implicated.3 Pseudomonads can be readily isolated from the environment and from patients where colonization of the mucosal surfaces is abnormal due to the acquisition and overgrowth of both endogenous and exogenous flora. Correspondence 01956701/92/030199+

to: Dr C. H. Webb,

Department

of Bacteriology,

10 $03.00,‘0

Royal

Victoria

Hospital,

0 1992 The Hosptal

199

Belfast,

UK.

Infection

Society

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P. J. Armstrong

et al.

Intensive care patients are thus predisposed to endogenous and nosocomial pseudomonad infections, particularly of the respiratory tract. In this study we examined Pseudomonas spp. isolated from patients and the environment during an IS-month, open, concurrent, controlled trial of SDD. A comparison was made of P. aeruginosa isolation, antibiotic resistance patterns and pyocine types in SDD patients, controls and the environment for evidence of cross-infection and clustering. Incidents of clinical infection were correlated with results. Materials

and methods

Study details Over an 18-month period 331 patients were included in the study.4 These were stratified by APACHE II score5 and randomized as SDD or control patients. Those patients selected for SDD received cefotaxime (50 mg kg-’ iv) for the first 4 days. Oropharyngeal administration of a gel day-’ containing tobramycin, 2% w/w, polymyxin B, 2% w/w and amphotericin solution containing the same B, 2% w/w, along with a nasogastric antibiotics in doses of 80 mg, 100 mg and 500 mg respectively, were given 6-hourly for the duration of the patient’s stay. The control patients were given antimicrobial treatment only as clinically indicated. Microbiological screening samples from the throat, gastric aspirate, tracheal secretions, urine and rectum were taken from all patients on admission and twice weekly thereafter. Additional specimens and blood cultures were taken as clinically indicated. The respiratory intensive care unit (RICU) sinks, humidifier water and breathing circuits, were also screened every 6 weeks. Identification, susceptibility testing and pyocine typing of P. aeruginosa All pseudomonads isolated were identified using the Sensititre Ltd). Antibiotic susceptibility Auto-identification System (Sensititre testing was performed on all strains by the Stokes disc diffusion method6 diagnostic sensitivity agar (DST, Oxoid, UK). Pseudomonas using aeyuginosa, NCTC 10662, was used as the control organism. Antibiotics used and their disc concentrations were as follows: azlocillin (30 pg); (5 pg); gentamicin (10 )Ig); netilmicin ceftazidime (30 pg); ciprofloxacin (30 l.tg); amikacin (10 pg); tobramycin (10 pg) and polymyxin B (300 pg). All inocula were adjusted to give semi-confluent growth. Resistance of a few selected strains was confirmed by minimum inhibitory concentration estimation (MIC) (Sensititre Ltd).7 Where repeat, successive isolates of P. aeruginosa from the same patient yielded the same antibiogram, a single representative strain was pyocine typed using the extended panel of indicator strains.* Using this selective procedure 31% of the total isolates from the controls and 51% from the SDD patients were pyocine typed. Repeated pyocine typing of the same strain consistently yielded the same pyocine type. Dates of admission, length of stay to first isolation of

Pseudomonas

pseudomonads patient.

aeruginosa

and episodes: of clinical

201

and SDD

infection

were recorded

for each

Definition of respiratory infection Clinical respiratory infection was defined as a temperature of more than 37..5”C, a white cell count of rnore than 12 or less than 4 X lo9 1-i and clinical signs of respiratory infection accompanied by new infiltrates on a chest X-ray. Infections in patients were divided into episodes where the patient’s stay could be punctuated by one or more periods of clinical resolution. Tracheal cultures were only an adjunct to diagnosis. Results

Patient isolates There were 161 patients, randomized to received SDD, and 170 controls. Pseudomonads were isolated from 44 (27%) SDD patients and 51 (30%) control patients. No significant difference in rectal colonization was observed between both patient groups, either on admission or throughout the patient stay. On admission 8% of SDD patients had pseudomonads isolated from the respiratory mucosae compared with 9% of controls. SDD partially controlled this colonization as their length of stay in the unit increased (Figure 1). Pseudomonads were rarely isolated from urine in either patient group.

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Figure 1. Percentage colonization in the oropharyngeal, Pseudomonas spp. n = SDD patients, H = controls.

tracheal

and gastric

specimens

by

P. J. Armstrong

202

et al.

Ninty-three per cent of all isolates were identified as P. aeruginosa, and all rectal isolates were P. aeruginosa. The non-aeruginosa pseudomonads were excluded from the rest of the analysis. Patient antibiograms Resistance in the rectal P. aeruginosa strains was uncommon in both patient groups. Tobramycin resistance was recorded in 12% of SDD patients and 13 % of controls. One control patient (no. 109), who entered the unit in February 1989, greatly influenced the number and antibiotic resistance of P. aeruginosa isolates recovered from non-rectal sites during her stay in the unit (February 1989 to April 1989). This patient was heavily colonized 5 days after admission to the unit by an aminoglycoside-resistant strain: resistant to gentamicin and netilmicin, sensitive to amikacin and resistant to tobramycin (denoted RRSR strain). Pseudomopad isolates displaying this pattern of resistance continued to be isolated throughout the trial. Figures 2 and 3 show the resistance of P. aeruginosa to tobramycin in both patient groups, gentamicin and netilmicin resistance following a similar pattern. This is due to 92% of the tobramycin resistant isolates being of the RRSR pattern in the SDD patients and 86% being of the same pattern in the controls. This RRSR pattern represented the majority of tobramycin resistance at all sampling times. Other tobramycin-resistance patterns -

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83

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Months

Figure 2. Tobramycin specimens from control with TOB-R isolates.

resistance patients.

of P. aeruginosa in tracheal, oropharyngeal n = TOB-R, q = total isolates, 0 = Number

and gastric of patients

Pseudomonasaeruginosa

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resistance of P. aeruginosa in tracheal, patients. (For key, see Figure 2).

oropharyngeal

and gastric

occurred rarely. Sixteen per cent of the isolates were ceftazidime resistant. Amikacin resistance was absent and resistance to ciprofloxacin was 5% in the SDD and 3% in the control patients. No resistance to polmyxin B was observed. The RRSR resistance pattern was often linked, in both patient groups, to azlocillin resistance (19’/, of isolates) or ceftazidime resistance (45%). Twenty-three per cent of RRSR isolates were resistant to both azlocillin and ceftazidime; only 13% were sensitive to both antibiotics. Environment

A total of 108 environmental isolates of pseudomonads were recovered. P. aeruginosa represented 77% of these isolates and their resistance to selected antibiotics is shown in Figure 4. Resistance was minimal until March 1989 when the aminoglycoside-resistant RRSR strain became endemic in the unit after the admission of patient no. 109. Forty-three (91%) of the tobramycin-resistant isolates were of the RRSR antibiogram pattern. No other tobramycin-resistance patterns remained in the environment. In total 37% of the P. aeruginosa isolates were tobramycin resistant. Amikacin resistance (1.7%) and ciprofloxacin resistance (6%) were uncommon. Twenty-six per cent were azlocillin resistant and 53% ceftazidime resistant. Seven per cent were resistant to both azlocillin and ceftazidime, and 14% were sensitive to both antibiotics.

P. J. Armstrong

204

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in environmental N = tobramycin.

isolates

of P.

aeruginosa. 0 = total isolates,

Patient pyocine types Twenty-four different pyocine types were identified in the control patients, the main types being NTf, lc and lx which together comprised 50% of the total. In the SDD group 21 different types were identified, 50% of which were either lx, 5k or lc. Other types in each group were isolated only sporadically (Figure 5). All eleven aminoglycoside-resistant strains (RRSR) selected from SDD patients were found to be type lx, and in the controls 13 out of 16 RRSR strains were typed as lx. Environmental pyocine types Eighty (90’/,) of the environmental P. aeruginosa typed. Of these, twenty-two different types were belonged to types lc, NTf, Sf, 29 and lx (Figure 6). aminoglycoside resistant strains (RRSR) were type

isolates were pyocine found, 67% of which Fifty-five (83%) of the lx.

Clinical signijkance of P. aeruginosa Pseudomonas aeruginosa were isolated from the tracheal secretions in 1.5 (9%) SDD patients and 22 (13%) controls. However, it was only responsible for respiratory tract infections in three SDD patients, no patient having recurring episodes of infection. Nine control patients had pseudomonad respiratory infections with two patients having recurring

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figures

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206

P. J. Armstrong

et al.

episodes, yielding a total of 13 episodes. Three episodes occurred at other sites in the controls and three in one SDD patient. In total, P. aeruginosa was implicated in six clinically significant episodes of infection in SDD patients and 16 in the control patients. No significant difference was observed in the time from admission to the first isolation of pseudomonads for both patient groups. However, the mean time to colonization in subsequently infected patients was 1.5 f 3-O days in the SDD patients and 4.4 f 4.2 days in the controls. This was accompanied by a mean time to infection in SDD patients of l-Of 2-O days and in controls of 4.3 f 6.0 days. In the SDD patients the isolates associated with infection were all aminoglycoside sensitive and of different pyocine types. In contrast, five (3 1%) of the episodes among control patients involved RRSR strains of P. aeruginosa which were of pyocine type lx. Four of these were from recurring episodes in patient no. 109. The sensitive strain, type lc, caused five episodes of infection, four in the control patients and one in an SDD patient. All other isolates were aminoglycoside sensitive and of different pyocine types. P. ueruginosu bacteraemia occurred in one SDD patient and in two controls. These were sensitive,strains and were of different pyocine types. Discussion

Because of the high risk of infection associated with P. ueruginosu in critically ill patients,’ it was important to consider the relative effect of the selective decontamination regimen on the rate of infection in the unit where control and SDD patient groups were nursed together. The results from this study have shown that pseudomonad colonization of respiratory sites in SDD treated patients is relatively reduced with increasing patient stay. The epidemiology of P. ueruginosu in the unit, however, did appear to be influenced by these patients. New strains of Pseudomonas spp. were frequently introduced to the unit but as 50% of these pseudomonads showing different pyocine types rarely occurred more than once, the majority of these strains did not become endemic. It would appear, however, that if a resistant strain such as the common RRSR aminoglycoside-resistant strain type lx is transferred to an SDD patient, it may become established due to altered colonization resistance of the patient and tobramycin resistance of the organism. An example of this was seen in February 1989 (Figure 5) when isolates of type lx were first detected in the unit after the admission of patient no. 109 and were subsequently transferred to SDD patients. This strain then became endemic in the unit. However, the RRSR strain type lx isolated in October 1988 and those of type NTf and lc were not transferred to an SDD patient and did not become endemic in the unit, suggesting that SDD patients may have served to promote the RRSR strain in the unit, particularly if the patients were long-stay and colonized in the upper respiratory tract. The same behaviour

Pseudomonas

aeruginosa

and SDD

207

was noted with the sensitive strain type lc, illustrating that establishment of antibiotic-sensitive strains in the SDD patients may also occur, the high concentrations of tobramycin and polymyxin B in the oropharyngeal mucosa not being an abso81ute barrier to colonization. We postulate, therefore, that type lc possesses other characteristics that promote its colonization and survival, and that these characteristics are more pronounced than in type Sk. Types lx and lc were also persistently isolated from the environment which may have provided an additional reservoir for these strains. The four other strains that showed marked persistence in the environment did not colonize the patients, despite possessing some aminoglycoside resistance. A reduction in the number of clinical pseudomonas infections in the SDD patients compared with the control group was observed, despite the fact that the SDD patients appeared to act as a reservoir for persistant strains. This protection in SDD patients,, however, was not absolute as those strains causing infection were both heterogeneous and sensitive. Indeed colonization and infection with P. aeruginosa in SDD patients occurred early. Therefore the strain vi,rulence is likely to be due to additional factors other than aminoglycoside resistance and independent of prolonged colonization. In contrast, ty,pe lx, five of which were the RRSR strain, caused six clinical infections in the control group, and in total 10 (63%) of the infections in this group were attributable to persistant strains. From this study, therefore, an important issue arises as to whether or not the frequency of these infections was increased due to the reservoir of strains maintained in the unit by the SDD patient group. We would conclude that this study emphasizes the fact that simultaneous management of both SDD and non-SDD patients in critical care demands that strict nosocomial infection control measures must be maintained. The authors would like to express sincere thanks to Mr G. M. Hogg for his help and support. The work has been funded by Hoechst/Roussel.

References 1. Ledingham IMcA, Alccock SR, Eastaway AT, McDonald JC, McKay IC, Ramsay G. Triple regime of selective decontamination of the digestive tract, systemic cefotaxime, and microbiological surveillance for prevention of acquired infection in intensive care. Lancet 1988; i: 785-790. 2. Stoutenbeck CP, van Saene HKF, Miranda DR, Zandstra DF. The effect of selective decontamination of the digestive tract on colonization and infection rate in multiple trauma patients. Intensive Care lnMed 1984: 10: 185-192. A. Clinical role of infrequently encountered non-fermenters. In: Gilardi 3. Von Graevenitz GL, Ed. Glucose Non-fermentinp Gram-nepative Bacteria in Clinical Microbiolopv.-0, West --Palm Beach, Florida: CRC Press Inc. 1978; 119-l 53. BJ, Lowry K, Webb CH, Armstrong PJ, Smilie J. Selective 4. Blair PH, Rowlands decontamination of the digestive tract: A stratified, randomized, prospective study in a mixed intensive care unit. Surgery 1991; 110: 303-310. 5. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985; 13: 818-829.

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6. Stokes EJ, Waterworth PM. Antibiotic sensitivity tests by diffusion methods. Association of Clinical Pathologists, Broadsheet No. 5.5 (revised) 1972. 7. Philips I, Warren C, Waterworth PM. Determination of antibiotic sensitivities by the Sensititre system. J Clin Puthol 1978; 31: 531-535. 8. Govan JRW. Pyocine typing of Pseudomonas aeruginosa. In: Bergan T, Norris J, Eds. Methods in Microbiology, VoZ 10. London: Academic Press 1975; 61-91. 9. Leonard EM, van Saene HKF, Stoutenbeck CP, Walker J, Tam PKH. An intrinsic pathogenicity index of microorganisms causing infection in a neonatal surgical unit Microbial Ecology in Health and Disease 1990; 3: 15 l-l 57.