journal
of Hospital
Infection
(1992) 20, 137-l 40
EDITORIAL
in hospital
Enterabacter
Enterobacter spp. were recognized as a minor cause of hospital infection in 1980.’ The emergence of E. cloacae as a hospital pathogen in America and the UK, has since been reviewed. 2,3 Enterobacter cloacae, in particular, has become an increasingly important cause of serious infection in immunocompromised patients.3,4’5 Accordingly, much attention has been paid to the development of suitable typing schemes3 which have facilitated epidemiological studies of the organism. Common source outbreaks are not often reported.‘j However, in the 198Os, outbreaks of cross-infection with E. cloacae defined by plasmid typing were described. In one, a retrospective study in 1983, before other typing methods were readily available,7 no common source was found and the other, more recently,’ was in a paediatric intensive care unit where distilled water was contaminated. In each instance, isolates from two separate consecutive outbreaks were distinguishable. The findings in the second report8 were confirmed by restriction endonuclease analysis. This is important because of the instability of the plasmids and because plasmid typing may identify an epidemic plasmid rather than an epidemic organism. Following our original study4 we investigated the epidemiology of Enterobacter in the hospitals served by our laboratory and in particular amongst the neutropenic patients from whom surveillance cultures were taken. In the haematology/oncology unit, E. cloacae had become a more common cause of bacteraemia in neutropenic patients than Pseudomonas aeruginosa.’ However, an unpublished examination of the most recent blood culture records from this unit reveals that this trend may be reversing and again P. aeruginosa and other Pseudomonas spp. are becoming more common. The reasons for this are unclear and require further investigation. Enterobacter cloacae was most commonly isolated from neutropenic patients for whom piperacillin and tobramycin have, for some time, formed the basis of the empirical antibiotic regimen. In the course of these two studies4s5 the resistance of the isolates of E. cloacae to these two agents rose from 65% and 24% to 81% and 67% respectively. The organism has not been evident in the burns unit where S-lactam agents are not widely used and where P. aeruginosa remains a commonly isolated Gram-negative bacillus. Epidemiological typing of our isolates of E. cloacae has not proved to be there has been little evidence of entirely straightforward. However, cross-infection.4l5 In this issue we report an outbreak in a small 0195-6701/92/030137+04S03.00/0
0 1992 The Hospital
137
Infection
Society
138
F. R. Falkiner
cardiothoracic ICU in which four patients yielded 29 isolates of E. cloacae, 19 of which were indistinguishable but were isolated from only two patients.’ More than one strain was isolated from all four patients. Amongst the neutropenic patients there was little evidence of cross-infection (or cross-colonization) and then only in patients who were in adjacent beds at the same time. There was no evidence of an epidemic plasmid. No E. cloacae were isolated from the environment and the bacteraemic isolates were all of different type.9 Recently, Weischer and Kolmos” reported their findings from a 6-year retrospective study in which they compared specific features of patients from whom they isolated Enterobacter spp. from blood culture with those yielding the first E. coli in blood culture of each month of the study. Their results indicate that burns patients and those with central venous catheters (mostly those with haematological malignancies) were the main groups of patients with enterobacter bacteraemia. Their findings are helpful, but perhaps of greater interest would have been a comparison of the enterobacter patients with those with pseudomonas bacteraemia. While our findings correspond to theirs in relation to neutropenic patients, this is not the case in the burns unit in our hospital where P. aeruginosa is commonly isolated, but Enterobacter is scarcely, if ever, found, particularly in blood culture. It is not possible to determine precisely why there should be this discrepancy. While it may be largely related to antibiotic usage there may also be differences in the approach to patient management. Because the study was retrospective it was not possible to type the isolates but, again, there seemed to be little evidence of cross-infection as the cases of bacteraemia were sporadic. The authors also associate enterobacter bacteraemia with invasive techniques such as peripheral or central venous catheters. It is quite possible though, that this is more a reflection of the severity of the illness and the treatment required, than a direct cause of bacteraemia. As the authors state, further work on the adherence of Enterobacter to such foreign bodies is required. Weischer and Kolmos” suggest that E. cloacae is of ‘nosocomial origin’. In the absence of the application of epidemiological typing, it is not certain that this is true. The sporadic nature of the cases of septicaemia and the frequency of polymicrobial cases suggest a faecal origin. Surveillance of the faecal cultures of our neutropenic patients has revealed that when a blood culture is positive for E. cloacae, the faeces cultured 2-3 weeks previously, sometimes prior to antibiotic therapy, yielded the same organism, often in pure culture.’ The absence of evidence of cross-infection suggests that E. cloacae is usually endogenously acquired. The production of a chromosomal class I P-lactamase by most members of the Enterobacteriaceae and by P. aeruginosa has been reviewed recently.” The emergence of de-repressed mutants was considered by Weischer and Kolmos” to be an important factor in the adaptation of E. cloacae to the hospital environment. This may well be true but does not entirely explain
Editorial
139
why it has overtaken Pseudomonas which has the same facility” or why other Enterobacteriaceae, such as Citrobacter freundii, are not more of a problem. Why E. cloacae did not emerge, until relatively recently, as an important cause of infection remains unanswered, though increasing resistance to aminoglycosides is likely to be an added advantage. However, strong evidence exists in an elegant study by Flynn et aZ.‘* which clearly relates to the emergence, or perhaps the selection, of E. cloacae in patients who received the first generation cephalosporin, cefazolin. From our experience, therefore, it would seem most likely that infection with E. cloacae is usually endogenously acquired and that patients carry their own strains in small numbers in their gastrointestinal tract; when they are treated with a p-lactam agent the organisms assume a new importance. When in neutropenic patients, the integrity of the mucous membranes of the intestinal or the respiratory tract, is damaged by cytotoxic therapy the organism can gain access to the bloodstream. The approach to the control of infection by Enterobacter, and indeed other Enterobacteriaceae such as Serratia, will depend on a better understanding of the factors important in the spread of the organisms. As Weischer and Kolmos suggest, studies of the adherence to foreign bodies are required. Further development of the epidemiological typing methods is necessary, and is continuing. 9,13 These should be applied in investigations of the carriage of the organisms, and related to the variety of invasive techniques used in the management of the patients apparently at greatest risk. Clearly, normal methods of infection control must continue to be applied but the difficulty of locating sources and reservoirs of Enterobacter and its apparent association with the use of p-lactam agents suggests that a more careful and considered approach to the use of antibiotics in critically ill patients is required. To achi’eve this, further basic epidemiological studies of Enterobacter are required, particularly in relation to p-lactam usage. It is likely that E. cloacae will continue to be a significant cause of hospital-acquired infection but that in most cases the organism will be errdogenously acquired; outbreaks of cross-infection will continue to be uncommon; and isolation of the organism from the environment will seldom be made. F. R. Falkiner
Department
of Clinical
Microbiology, Trinity College Dublin, St. James’s Hospital, Dublin 8, Ireland
References 1. National Survey of Infection in Hospitals, 1980. J Hosp Infect 1981; 2: Suppl. 13-17. RJ, Bannister ER. Enterobacter cloacae: Bacteremia, epidemiology 2. John JF, Sharbaugh and antibiotic resistance. Rev Infect Dis 1982; 4: 13-27. an emerging nosocomial pathogen. j' Hosp Infect 1988; 11: 3. Gaston MA. Enterobacter: 197-208.
140
F. R. Falkiner
4. McConkey SJ, Coleman DC, Falkiner FR, McCann SR, Daly PA. Enterobacter cloacae in a haematology/oncology ward-first impressions. J Hosp Infect 1989; 14: 277-284. 5. Daw MA, Munnelly P. McCann SR, Daly PA, Falkiner FR, Keane CT. Value of surveillance cultures in the management of neutropenic patients. Eur J Clin Microbial Infect Dis 1988; 7: 742-747. 6. Gaston MA, Crees-Morris JA, Pitt TL. Serotype and biochemical profiles of British hospital strains of Enterobacter cloacae in relation to site of infection and antibiotic susceptibility. J Infect Dis 1987; 10: 17-27. 7. Markowitz SM, Smith SM, Williams DS. Retrospective analysis of plasmid patterns in a study of burns unit outbreaks of infection due to Enterobacter cloacae. JInfect Dis 1983; 1: 18-23. of plasmid pattern in paediatric 8. Wang CC, Chu ML, Ho LJ H wang RC. Analysis intensive care unit outbreaks of nosocomial infection due to Enterobacter cloacae. J Hosp Infect 1991; 19: 3340. 9. Daw MA, Corcoran CD, Falkiner FR, Keane CT. Application and assessment of cloacin typing of Enterobacter cloacae. J Hasp Infect 1992; 20: 141-l 51. 10. Weischer M, Kolmos HJ. Retrospective 6-year study of Enterobacter bacteraemia in a Danish university hospital. r Hosp Infect 1992; 20: 15-24. 11. Lodge JM, Piddock LJV. The control of Class 1 J3-lactamase expression in Enterobacteriaceae and Pseudomonas aeruginosa. J Antimicrob Chemother 1991; 28: 167-172. 12. Flynn DM, Weinstein RA, Nathan C, Gaston MA, Kabins, SA. Patients’ endogenous flora as a source of ‘nosocomial’ Enterobacter in cardiac surgery. J Infect Dis 1987; 156: 363-368. 13. Garaizar J, Kaufmann ME, Pitt TL. Comparison of ribotyping with conventional methods for the type identification of Enterobacter cloacae. J Clin Microbial 1991; 29: 1303-I 307.
of Hospital
Infection
(1992) 20, 137-l 40
EDITORIAL
in hospital
Enterabacter
Enterobacter spp. were recognized as a minor cause of hospital infection in 1980.’ The emergence of E. cloacae as a hospital pathogen in America and the UK, has since been reviewed. 2,3 Enterobacter cloacae, in particular, has become an increasingly important cause of serious infection in immunocompromised patients.3,4’5 Accordingly, much attention has been paid to the development of suitable typing schemes3 which have facilitated epidemiological studies of the organism. Common source outbreaks are not often reported.‘j However, in the 198Os, outbreaks of cross-infection with E. cloacae defined by plasmid typing were described. In one, a retrospective study in 1983, before other typing methods were readily available,7 no common source was found and the other, more recently,’ was in a paediatric intensive care unit where distilled water was contaminated. In each instance, isolates from two separate consecutive outbreaks were distinguishable. The findings in the second report8 were confirmed by restriction endonuclease analysis. This is important because of the instability of the plasmids and because plasmid typing may identify an epidemic plasmid rather than an epidemic organism. Following our original study4 we investigated the epidemiology of Enterobacter in the hospitals served by our laboratory and in particular amongst the neutropenic patients from whom surveillance cultures were taken. In the haematology/oncology unit, E. cloacae had become a more common cause of bacteraemia in neutropenic patients than Pseudomonas aeruginosa.’ However, an unpublished examination of the most recent blood culture records from this unit reveals that this trend may be reversing and again P. aeruginosa and other Pseudomonas spp. are becoming more common. The reasons for this are unclear and require further investigation. Enterobacter cloacae was most commonly isolated from neutropenic patients for whom piperacillin and tobramycin have, for some time, formed the basis of the empirical antibiotic regimen. In the course of these two studies4s5 the resistance of the isolates of E. cloacae to these two agents rose from 65% and 24% to 81% and 67% respectively. The organism has not been evident in the burns unit where S-lactam agents are not widely used and where P. aeruginosa remains a commonly isolated Gram-negative bacillus. Epidemiological typing of our isolates of E. cloacae has not proved to be there has been little evidence of entirely straightforward. However, cross-infection.4l5 In this issue we report an outbreak in a small 0195-6701/92/030137+04S03.00/0
0 1992 The Hospital
137
Infection
Society
138
F. R. Falkiner
cardiothoracic ICU in which four patients yielded 29 isolates of E. cloacae, 19 of which were indistinguishable but were isolated from only two patients.’ More than one strain was isolated from all four patients. Amongst the neutropenic patients there was little evidence of cross-infection (or cross-colonization) and then only in patients who were in adjacent beds at the same time. There was no evidence of an epidemic plasmid. No E. cloacae were isolated from the environment and the bacteraemic isolates were all of different type.9 Recently, Weischer and Kolmos” reported their findings from a 6-year retrospective study in which they compared specific features of patients from whom they isolated Enterobacter spp. from blood culture with those yielding the first E. coli in blood culture of each month of the study. Their results indicate that burns patients and those with central venous catheters (mostly those with haematological malignancies) were the main groups of patients with enterobacter bacteraemia. Their findings are helpful, but perhaps of greater interest would have been a comparison of the enterobacter patients with those with pseudomonas bacteraemia. While our findings correspond to theirs in relation to neutropenic patients, this is not the case in the burns unit in our hospital where P. aeruginosa is commonly isolated, but Enterobacter is scarcely, if ever, found, particularly in blood culture. It is not possible to determine precisely why there should be this discrepancy. While it may be largely related to antibiotic usage there may also be differences in the approach to patient management. Because the study was retrospective it was not possible to type the isolates but, again, there seemed to be little evidence of cross-infection as the cases of bacteraemia were sporadic. The authors also associate enterobacter bacteraemia with invasive techniques such as peripheral or central venous catheters. It is quite possible though, that this is more a reflection of the severity of the illness and the treatment required, than a direct cause of bacteraemia. As the authors state, further work on the adherence of Enterobacter to such foreign bodies is required. Weischer and Kolmos” suggest that E. cloacae is of ‘nosocomial origin’. In the absence of the application of epidemiological typing, it is not certain that this is true. The sporadic nature of the cases of septicaemia and the frequency of polymicrobial cases suggest a faecal origin. Surveillance of the faecal cultures of our neutropenic patients has revealed that when a blood culture is positive for E. cloacae, the faeces cultured 2-3 weeks previously, sometimes prior to antibiotic therapy, yielded the same organism, often in pure culture.’ The absence of evidence of cross-infection suggests that E. cloacae is usually endogenously acquired. The production of a chromosomal class I P-lactamase by most members of the Enterobacteriaceae and by P. aeruginosa has been reviewed recently.” The emergence of de-repressed mutants was considered by Weischer and Kolmos” to be an important factor in the adaptation of E. cloacae to the hospital environment. This may well be true but does not entirely explain
Editorial
139
why it has overtaken Pseudomonas which has the same facility” or why other Enterobacteriaceae, such as Citrobacter freundii, are not more of a problem. Why E. cloacae did not emerge, until relatively recently, as an important cause of infection remains unanswered, though increasing resistance to aminoglycosides is likely to be an added advantage. However, strong evidence exists in an elegant study by Flynn et aZ.‘* which clearly relates to the emergence, or perhaps the selection, of E. cloacae in patients who received the first generation cephalosporin, cefazolin. From our experience, therefore, it would seem most likely that infection with E. cloacae is usually endogenously acquired and that patients carry their own strains in small numbers in their gastrointestinal tract; when they are treated with a p-lactam agent the organisms assume a new importance. When in neutropenic patients, the integrity of the mucous membranes of the intestinal or the respiratory tract, is damaged by cytotoxic therapy the organism can gain access to the bloodstream. The approach to the control of infection by Enterobacter, and indeed other Enterobacteriaceae such as Serratia, will depend on a better understanding of the factors important in the spread of the organisms. As Weischer and Kolmos suggest, studies of the adherence to foreign bodies are required. Further development of the epidemiological typing methods is necessary, and is continuing. 9,13 These should be applied in investigations of the carriage of the organisms, and related to the variety of invasive techniques used in the management of the patients apparently at greatest risk. Clearly, normal methods of infection control must continue to be applied but the difficulty of locating sources and reservoirs of Enterobacter and its apparent association with the use of p-lactam agents suggests that a more careful and considered approach to the use of antibiotics in critically ill patients is required. To achi’eve this, further basic epidemiological studies of Enterobacter are required, particularly in relation to p-lactam usage. It is likely that E. cloacae will continue to be a significant cause of hospital-acquired infection but that in most cases the organism will be errdogenously acquired; outbreaks of cross-infection will continue to be uncommon; and isolation of the organism from the environment will seldom be made. F. R. Falkiner
Department
of Clinical
Microbiology, Trinity College Dublin, St. James’s Hospital, Dublin 8, Ireland
References 1. National Survey of Infection in Hospitals, 1980. J Hosp Infect 1981; 2: Suppl. 13-17. RJ, Bannister ER. Enterobacter cloacae: Bacteremia, epidemiology 2. John JF, Sharbaugh and antibiotic resistance. Rev Infect Dis 1982; 4: 13-27. an emerging nosocomial pathogen. j' Hosp Infect 1988; 11: 3. Gaston MA. Enterobacter: 197-208.
140
F. R. Falkiner
4. McConkey SJ, Coleman DC, Falkiner FR, McCann SR, Daly PA. Enterobacter cloacae in a haematology/oncology ward-first impressions. J Hosp Infect 1989; 14: 277-284. 5. Daw MA, Munnelly P. McCann SR, Daly PA, Falkiner FR, Keane CT. Value of surveillance cultures in the management of neutropenic patients. Eur J Clin Microbial Infect Dis 1988; 7: 742-747. 6. Gaston MA, Crees-Morris JA, Pitt TL. Serotype and biochemical profiles of British hospital strains of Enterobacter cloacae in relation to site of infection and antibiotic susceptibility. J Infect Dis 1987; 10: 17-27. 7. Markowitz SM, Smith SM, Williams DS. Retrospective analysis of plasmid patterns in a study of burns unit outbreaks of infection due to Enterobacter cloacae. JInfect Dis 1983; 1: 18-23. of plasmid pattern in paediatric 8. Wang CC, Chu ML, Ho LJ H wang RC. Analysis intensive care unit outbreaks of nosocomial infection due to Enterobacter cloacae. J Hosp Infect 1991; 19: 3340. 9. Daw MA, Corcoran CD, Falkiner FR, Keane CT. Application and assessment of cloacin typing of Enterobacter cloacae. J Hasp Infect 1992; 20: 141-l 51. 10. Weischer M, Kolmos HJ. Retrospective 6-year study of Enterobacter bacteraemia in a Danish university hospital. r Hosp Infect 1992; 20: 15-24. 11. Lodge JM, Piddock LJV. The control of Class 1 J3-lactamase expression in Enterobacteriaceae and Pseudomonas aeruginosa. J Antimicrob Chemother 1991; 28: 167-172. 12. Flynn DM, Weinstein RA, Nathan C, Gaston MA, Kabins, SA. Patients’ endogenous flora as a source of ‘nosocomial’ Enterobacter in cardiac surgery. J Infect Dis 1987; 156: 363-368. 13. Garaizar J, Kaufmann ME, Pitt TL. Comparison of ribotyping with conventional methods for the type identification of Enterobacter cloacae. J Clin Microbial 1991; 29: 1303-I 307.
