- Email: [email protected]
Pseudomonas aeruginosa orbital cellulitis in four neutropenic patients
Journal
of Hospital
Infection
(1990)
16, 343-349
SHORT REPORT
Pseudomonas
aeruginosa neutropenic
M. C. Atkins*,
orbital cellulitis patients
G. A. J. Harrison*,
in four
and G. S. Lucas**
Departments of *Medical Microbiology and **Haematology, University Hospital of Wales, Heath Park, Cardiff CF4 4XN Accepted for publication
12 July 1990
Summary:
Four neutropenic patients on a haematology ward developed orbital cellulitis due to different strains of Pseudomonas aeruginosa over a 7month period. Investigation of patients and the ward environment revealed two P. aeruginosa isolates indistinguishable from the infecting strains in a plastic washing bowl and a sink in a single cubicle respectively. These items were unlikely to have been the sources of the infecting strains but were a potential cross infection hazard. Treatment of orbital cellulitis is discussed briefly.
Keywords:
Pseudomonas aeruginosa; orbital
cellulitis;
neutropenia.
Introduction Infection with Pseudomonas aeruginosa remains one of the major causes of morbidity and mortality in neutropenic patients (Van der Meer, Alleman & Boekhart, 1979; Gaya, 1986). Pseudomonas aeruginosa is an important aetiological agent in a variety of disorders of the eye and surrounding tissues (Kreger, 1983). Predisposing factors include surgery, trauma, pre-existing ocular disease and immunosuppressive therapy (Rosenhoff, Wolf & Chabner, 1974). We report four patients with orbital cellulitis due to strains of P. aeruginosa. The occurrence of two cases simultaneously led us to investigate possible sources of P. aeruginosa. Patients and methods The patients were, or had recently been, present on the same haematology ward (Figure 1). The ward consists of a 4-bedded unit, three 2-bedded units and six single cubicles. Patient details are given in Table I. The patients, all Correspondence
to: M.
C. Atkins.
0195%6701/90/0X0343
+OJ $03.00/O
0 1990 The Hospital
343
Infection
Soaety
M. C. Atkins
344
Patient
1
Patient
2
Pafient
3
Patient
4
I
I
I
Nov
Ott
et al.
Dee
Jan 1989
1988
Figure
Time on Haema
1. Development
tokqy
of cases
of
Unit
I
Mar
APr
Ward
0
I
Feb survay
mT1 Duration
P. aeruginosa
orbital
of orbital
cellulitis
cellulitis
with
time.
with acute myeloid leukaemia, developed severe orbital cellulitis (Figures 2, 3) in association with profound neutropenia (< 0.1 x lo9 1-l) of > 7 days duration. Patients 1 and 2 also had septicaemia. There was no evidence of pre-existing ocular disease. None of the patients developed cornea1 ulceration or intraocular sepsis but some impairment of ocular movements and visual acuity was noted. Patient 1 was colonized with P. aeruginosa in June 1988 when this organism was isolated from eye swabs and urine, although she had no symptoms of infection at that time. Because of the serious nature of these infections, and the close proximity in time of onset, environmental sampling of the ward was undertaken. Samples were taken from the fixtures, fittings and medical equipment (110 samples). Particular attention was paid to moist areas such as sinks, baths, face cloths and showers. Rectal and throat swabs were taken from eight of the ten patients on the ward. Swabs were inoculated onto Pseudomonas Isolation Agar (Difco) and 5% horse blood agar. Samples from cleaning cloths, mops, mouth washes and ophthalmic preparations were inoculated into Mueller-Hinton broth. Disinfectants, cleaning fluids and hand cleansing agents were inoculated, in 100 ~1 aliquots, into 50ml of Mueller-Hinton broth with added lecithin, Tween-80 and sodium thiosulphate (Ayliffe, Babb & Quoraishi, 1978).
3 17 yrs
bowl
Patient male
in room
Plastic
Sink
Q:6
0:6
gentamicin;
l/b
3/x
3/x
3/x
3/x
type
I. Patient
N/A
Pyocine
Patient 4 0:ll female 61 yrs __ * Typing reaction of + + or stronger. ** Azl, Azlocillin; Cef, ceftazidime; Gen, N/A, not available.
41
0:6
2 35 yrs
Patient male
0:6
N/A
Serotype
Patient 1 female 66 yrs
Source
Table
Neo,
type*
and
neomycin;
N/A
Tob,
profile
results
tobramycin.
N/A
1054575
1054575
1054575
1054575
N/A
API
typing
16, 44, F8, 109, 1214, M4
7, 21, 68
7, 68
16, 44, F8, 109, 352, 1214, M4
N/A
Phage
details features
cellulitis
Conjunctivitis orbital cellulitis
~~
-
Orbital
Conjunctivitis orbital cellulitis
&
&
isolates
Orbital cellulitis & ecthyma gangrenosum
Ocular
of P. aeruginosa
Cef, Gen & topical Neo
Azl, Gen & topical Neo
Azl, Gen & topical Neo
Cef! Tob & topical Neo
Antimicrobial therapy**
Cellulitis
Cellulitis
Cellulitis improved patient
Cellulitis
resolved
resolved
resolved
but died
Outcome
8 e(: e: g.
;: F FL
0
B 2 3. : B
P
M. C. Atkins
346
Figure
2. Orbital
Figure
cellulitik
3. Orbital
affecting
cellulitis
et al.
the
right
in patient
eye of patient
2.
1.
P. aeruginosa
orbital
cellulitis
347
Broths were subcultured to Pseudomonas Isolation Agar and blood agar on alternate days for 1 week. Water samples from outlets on the ward were also examined for the presence of P. aeruginosa (Department of the Environment et al., 1982). Pigment producing, oxidase positive colonies were identified as P. aeruginosa by” standard confirmatory tests. Antibiotic sensitivity testing was performed by a comparative disc diffusion method on DST agar (Oxoid). Serotyping was performed using commercially available sera (Difco). Pyocine type was determined by the method of Govan & Gillies (1969). Phage typing was kindly performed by the Division of Hospital Infection, Central Public Health Laboratory, Colindale. Biotyping of serotype 0:6 isolates was performed using the API 20NE system (API Products Ltd). Results Eye swabs from patients 2 and 3 grew serotype 0:6 P. aeruginosa. Of the 110 environmental samples, 16 (14.5 O/o) were positive for P. aeruginosa. These were isolated from eight (42%) of 19 sinks, the bath, one of two plastic washing bowls, two face cloths and four from mops and buckets used for floor cleaning. As case 4 had not occurred by the time of the ward survey, further typing was only performed on 0:6 isolates (Table I). Pseudomonas aeruginosa was not isolated from any of the water supply outlets or from other patients on the ward. All patient isolates were sensitive to azlocillin, ceftazidime, gentamicin, neomycin and tobramycin. Discussion Profound neutropenia is one of the most important factors predisposing patients with leukaemia to pseudomonas infection (Van der Meer et al., 1979). Colonization with P. aeruginosa is a common finding and often precedes infection. It has also been shown that up to 47% of patients acquire the infecting strains in hospital (Schimpff et al., 1972). The typing results indicate that the infections were caused by different strains. However, the strain from the sink in room 41 and patient 2 are similar, as are the strains from patient 3 and the plastic washing bowl. It is unlikely that the washing bowl and the sink were the sources of the infecting strains but must be regarded as hazards to other patients. It was recommended that separate -washing bowls were provided for each patient and that these were thoroughly washed and dried after use (Joynson, 1978). Sterile disposable face cloths were also provided. Sinks were cleaned regularly with bleaching powder. Mops with detachable heads were supplied that could be washed with detergent and dried after use. During the course of the investigation, every opportunity was taken to
348
M. C. Atkins
et al.
reinforce infection control procedures and all reasonable measures were taken to further reduce colonization of the environment with P. aeruginosa. Patient management, chemotherapy and antibiotic regimens had not been significantly altered during this period. No further cases of orbital cellulitis have developed to date. Orbital cellulitis is primarily a disease of children and is commonly associated with sinusitis. It is rarely due to P. aerugirzosa (Weiss, 1979). This is a serious condition which must be treated promptly and aggressively if the complications of cornea1 ulceration, panophthalmitis and cavernous sinus thrombosis are to be avoided. Rapid development of panophthalmitis has been attributed to the elaboration of proteolytic enzymes by P. aeruginosa and from polymorphonuclear leukocytes that infiltrate the infected cornea (Kreger, 1983). Treatment should include systemic and topical anti-pseudomonal agents, It is often recommended that a potentially synergistic P-lactam-aminoglycoside combination is used as this may be more effective in treating P. aeruginosa infection in neutropenic patients than a single or double p-lactam regimen (Dejace & Klastersky, 1986). There is some evidence from animal studies and case reports (Bakker-Woudenberg & Roosendaal, 1988; Dahnen & de Vries-Hospers, 1988) that continuous infusion of p-lactams can be more effective in treating Gram-negative infections than intermittent dosing. These results might be explained by the in-vitro observations that: (i) the post antibiotic effect, i.e. the prolonged inhibition of bacterial growth after limited exposure to an antibiotic, is very short for most p-lactams against Gram-negative bacilli, and (ii) bacterial killing is more dependent on the duration of active antibiotic levels than on the peak concentration (Vogelman & Craig, 1986). This approach offers some advantages in experimental models but greater clinical experience is required. We thank Dr C. D. Ribeiro, PHLS, Cardiff for pyocine typing, and PHLS Gram Negative Reference Unit, Colindale for phage typing data. We are grateful to Dr J. A. Whittaker and Dr C. H. Poynton for allowing us to report on patients under their care and to Miss Doreen Matthew and Mr D. Hill for their assistance.
References A. H. (1978). A test for ‘hygienic’ hand G. A. J., Babb, J. R. & Q uoraishi, disinfection. Yournal of Clinical Patholopv 31. 923-928. Bakker-WoudenbGrg, I. A-J. M. & Roosend&l, R: (1988). Impact of dosage regimens on the efficacy of antibiotics in the immunocompromised host. Journal of Antimicrobial Chemotherapy 21, 145-l 50. Dahnen. S. & De Vries-Hosners, H. (1988). Cure of Pseudomonas aeruninosa infection in neutropenic patients by continuous infusion of ceftazidime. Lancet i, 937. Dejace, P. & Klastersky, J. (1986). Comparative review of combination therapy: two plactams versus J3-lactam plus aminoglycoside. American Journal of Medicine 80 (Suppl. 6B), 29-38. Department of the Environment, Department of Health and Social Security & Public Health Laboratory Service (1982). The test for Pseudomonas aeruginosa. In The Bacteriological Examination of Drinking Water Supplies 1982, 5th edn, pp. 55-57. London: HMSO. Ayliffe,
P. aeruginosa Gaya,
orbital
cellulitis
349
H. (1986). Combination therapy and monotherapy in the treatment of severe infection in the immunocompromised host. American Journal of Medicine 80 (Suppl. 6B), 149-155. Govan, J. R. W. & Gillies, R. R. (1969). Further studies in the pyocine typing of Pseudomonas pyocyanea. Journal of Medical Microbiology 2, 17-25. Joynson, D. H. M. (1978). Bowls and bacteria. Journal of Hygiene 80, 423-425. Kreger, A. S. (1983). Pathogenesis of Pseudomonas aeruginosa ocular disease. Reviews of Infectious Diseases 5 (Suppl. S), 931-934. Rosenhoff, S., Wolf, M. L. & Chabner, B. A. (1974). Pseudomonas blepharoconjunctivitis: a complication of combination chemotherapy. Archives of Ophthalmology 91, 490491. Schimpff, S. C., Young, V. M., Greene, W. H., Vermeulen, G. D., Moody, M. S. & Wiernik, P. H. (1972). Origin of infection in nonlymphocytic leukemia. Annals of Internal Medicine 77, 707-714. Van der Meer, J. W. M., Alleman, M. & Boekhart, M. (1979). Infectious episodes in severely neutropenic patients. Infection 7, 171-175. Vogelman, B. & Craig, W. A. (1986). Kinetics of antimicrobial activity. Journal of Pediatrics 108, 835-840. Weiss, I. S. (1979). Pseudomonas orbital cellulitis. American Journal of Ophthalmology 87, 368-370.
of Hospital
Infection
(1990)
16, 343-349
SHORT REPORT
Pseudomonas
aeruginosa neutropenic
M. C. Atkins*,
orbital cellulitis patients
G. A. J. Harrison*,
in four
and G. S. Lucas**
Departments of *Medical Microbiology and **Haematology, University Hospital of Wales, Heath Park, Cardiff CF4 4XN Accepted for publication
12 July 1990
Summary:
Four neutropenic patients on a haematology ward developed orbital cellulitis due to different strains of Pseudomonas aeruginosa over a 7month period. Investigation of patients and the ward environment revealed two P. aeruginosa isolates indistinguishable from the infecting strains in a plastic washing bowl and a sink in a single cubicle respectively. These items were unlikely to have been the sources of the infecting strains but were a potential cross infection hazard. Treatment of orbital cellulitis is discussed briefly.
Keywords:
Pseudomonas aeruginosa; orbital
cellulitis;
neutropenia.
Introduction Infection with Pseudomonas aeruginosa remains one of the major causes of morbidity and mortality in neutropenic patients (Van der Meer, Alleman & Boekhart, 1979; Gaya, 1986). Pseudomonas aeruginosa is an important aetiological agent in a variety of disorders of the eye and surrounding tissues (Kreger, 1983). Predisposing factors include surgery, trauma, pre-existing ocular disease and immunosuppressive therapy (Rosenhoff, Wolf & Chabner, 1974). We report four patients with orbital cellulitis due to strains of P. aeruginosa. The occurrence of two cases simultaneously led us to investigate possible sources of P. aeruginosa. Patients and methods The patients were, or had recently been, present on the same haematology ward (Figure 1). The ward consists of a 4-bedded unit, three 2-bedded units and six single cubicles. Patient details are given in Table I. The patients, all Correspondence
to: M.
C. Atkins.
0195%6701/90/0X0343
+OJ $03.00/O
0 1990 The Hospital
343
Infection
Soaety
M. C. Atkins
344
Patient
1
Patient
2
Pafient
3
Patient
4
I
I
I
Nov
Ott
et al.
Dee
Jan 1989
1988
Figure
Time on Haema
1. Development
tokqy
of cases
of
Unit
I
Mar
APr
Ward
0
I
Feb survay
mT1 Duration
P. aeruginosa
orbital
of orbital
cellulitis
cellulitis
with
time.
with acute myeloid leukaemia, developed severe orbital cellulitis (Figures 2, 3) in association with profound neutropenia (< 0.1 x lo9 1-l) of > 7 days duration. Patients 1 and 2 also had septicaemia. There was no evidence of pre-existing ocular disease. None of the patients developed cornea1 ulceration or intraocular sepsis but some impairment of ocular movements and visual acuity was noted. Patient 1 was colonized with P. aeruginosa in June 1988 when this organism was isolated from eye swabs and urine, although she had no symptoms of infection at that time. Because of the serious nature of these infections, and the close proximity in time of onset, environmental sampling of the ward was undertaken. Samples were taken from the fixtures, fittings and medical equipment (110 samples). Particular attention was paid to moist areas such as sinks, baths, face cloths and showers. Rectal and throat swabs were taken from eight of the ten patients on the ward. Swabs were inoculated onto Pseudomonas Isolation Agar (Difco) and 5% horse blood agar. Samples from cleaning cloths, mops, mouth washes and ophthalmic preparations were inoculated into Mueller-Hinton broth. Disinfectants, cleaning fluids and hand cleansing agents were inoculated, in 100 ~1 aliquots, into 50ml of Mueller-Hinton broth with added lecithin, Tween-80 and sodium thiosulphate (Ayliffe, Babb & Quoraishi, 1978).
3 17 yrs
bowl
Patient male
in room
Plastic
Sink
Q:6
0:6
gentamicin;
l/b
3/x
3/x
3/x
3/x
type
I. Patient
N/A
Pyocine
Patient 4 0:ll female 61 yrs __ * Typing reaction of + + or stronger. ** Azl, Azlocillin; Cef, ceftazidime; Gen, N/A, not available.
41
0:6
2 35 yrs
Patient male
0:6
N/A
Serotype
Patient 1 female 66 yrs
Source
Table
Neo,
type*
and
neomycin;
N/A
Tob,
profile
results
tobramycin.
N/A
1054575
1054575
1054575
1054575
N/A
API
typing
16, 44, F8, 109, 1214, M4
7, 21, 68
7, 68
16, 44, F8, 109, 352, 1214, M4
N/A
Phage
details features
cellulitis
Conjunctivitis orbital cellulitis
~~
-
Orbital
Conjunctivitis orbital cellulitis
&
&
isolates
Orbital cellulitis & ecthyma gangrenosum
Ocular
of P. aeruginosa
Cef, Gen & topical Neo
Azl, Gen & topical Neo
Azl, Gen & topical Neo
Cef! Tob & topical Neo
Antimicrobial therapy**
Cellulitis
Cellulitis
Cellulitis improved patient
Cellulitis
resolved
resolved
resolved
but died
Outcome
8 e(: e: g.
;: F FL
0
B 2 3. : B
P
M. C. Atkins
346
Figure
2. Orbital
Figure
cellulitik
3. Orbital
affecting
cellulitis
et al.
the
right
in patient
eye of patient
2.
1.
P. aeruginosa
orbital
cellulitis
347
Broths were subcultured to Pseudomonas Isolation Agar and blood agar on alternate days for 1 week. Water samples from outlets on the ward were also examined for the presence of P. aeruginosa (Department of the Environment et al., 1982). Pigment producing, oxidase positive colonies were identified as P. aeruginosa by” standard confirmatory tests. Antibiotic sensitivity testing was performed by a comparative disc diffusion method on DST agar (Oxoid). Serotyping was performed using commercially available sera (Difco). Pyocine type was determined by the method of Govan & Gillies (1969). Phage typing was kindly performed by the Division of Hospital Infection, Central Public Health Laboratory, Colindale. Biotyping of serotype 0:6 isolates was performed using the API 20NE system (API Products Ltd). Results Eye swabs from patients 2 and 3 grew serotype 0:6 P. aeruginosa. Of the 110 environmental samples, 16 (14.5 O/o) were positive for P. aeruginosa. These were isolated from eight (42%) of 19 sinks, the bath, one of two plastic washing bowls, two face cloths and four from mops and buckets used for floor cleaning. As case 4 had not occurred by the time of the ward survey, further typing was only performed on 0:6 isolates (Table I). Pseudomonas aeruginosa was not isolated from any of the water supply outlets or from other patients on the ward. All patient isolates were sensitive to azlocillin, ceftazidime, gentamicin, neomycin and tobramycin. Discussion Profound neutropenia is one of the most important factors predisposing patients with leukaemia to pseudomonas infection (Van der Meer et al., 1979). Colonization with P. aeruginosa is a common finding and often precedes infection. It has also been shown that up to 47% of patients acquire the infecting strains in hospital (Schimpff et al., 1972). The typing results indicate that the infections were caused by different strains. However, the strain from the sink in room 41 and patient 2 are similar, as are the strains from patient 3 and the plastic washing bowl. It is unlikely that the washing bowl and the sink were the sources of the infecting strains but must be regarded as hazards to other patients. It was recommended that separate -washing bowls were provided for each patient and that these were thoroughly washed and dried after use (Joynson, 1978). Sterile disposable face cloths were also provided. Sinks were cleaned regularly with bleaching powder. Mops with detachable heads were supplied that could be washed with detergent and dried after use. During the course of the investigation, every opportunity was taken to
348
M. C. Atkins
et al.
reinforce infection control procedures and all reasonable measures were taken to further reduce colonization of the environment with P. aeruginosa. Patient management, chemotherapy and antibiotic regimens had not been significantly altered during this period. No further cases of orbital cellulitis have developed to date. Orbital cellulitis is primarily a disease of children and is commonly associated with sinusitis. It is rarely due to P. aerugirzosa (Weiss, 1979). This is a serious condition which must be treated promptly and aggressively if the complications of cornea1 ulceration, panophthalmitis and cavernous sinus thrombosis are to be avoided. Rapid development of panophthalmitis has been attributed to the elaboration of proteolytic enzymes by P. aeruginosa and from polymorphonuclear leukocytes that infiltrate the infected cornea (Kreger, 1983). Treatment should include systemic and topical anti-pseudomonal agents, It is often recommended that a potentially synergistic P-lactam-aminoglycoside combination is used as this may be more effective in treating P. aeruginosa infection in neutropenic patients than a single or double p-lactam regimen (Dejace & Klastersky, 1986). There is some evidence from animal studies and case reports (Bakker-Woudenberg & Roosendaal, 1988; Dahnen & de Vries-Hospers, 1988) that continuous infusion of p-lactams can be more effective in treating Gram-negative infections than intermittent dosing. These results might be explained by the in-vitro observations that: (i) the post antibiotic effect, i.e. the prolonged inhibition of bacterial growth after limited exposure to an antibiotic, is very short for most p-lactams against Gram-negative bacilli, and (ii) bacterial killing is more dependent on the duration of active antibiotic levels than on the peak concentration (Vogelman & Craig, 1986). This approach offers some advantages in experimental models but greater clinical experience is required. We thank Dr C. D. Ribeiro, PHLS, Cardiff for pyocine typing, and PHLS Gram Negative Reference Unit, Colindale for phage typing data. We are grateful to Dr J. A. Whittaker and Dr C. H. Poynton for allowing us to report on patients under their care and to Miss Doreen Matthew and Mr D. Hill for their assistance.
References A. H. (1978). A test for ‘hygienic’ hand G. A. J., Babb, J. R. & Q uoraishi, disinfection. Yournal of Clinical Patholopv 31. 923-928. Bakker-WoudenbGrg, I. A-J. M. & Roosend&l, R: (1988). Impact of dosage regimens on the efficacy of antibiotics in the immunocompromised host. Journal of Antimicrobial Chemotherapy 21, 145-l 50. Dahnen. S. & De Vries-Hosners, H. (1988). Cure of Pseudomonas aeruninosa infection in neutropenic patients by continuous infusion of ceftazidime. Lancet i, 937. Dejace, P. & Klastersky, J. (1986). Comparative review of combination therapy: two plactams versus J3-lactam plus aminoglycoside. American Journal of Medicine 80 (Suppl. 6B), 29-38. Department of the Environment, Department of Health and Social Security & Public Health Laboratory Service (1982). The test for Pseudomonas aeruginosa. In The Bacteriological Examination of Drinking Water Supplies 1982, 5th edn, pp. 55-57. London: HMSO. Ayliffe,
P. aeruginosa Gaya,
orbital
cellulitis
349
H. (1986). Combination therapy and monotherapy in the treatment of severe infection in the immunocompromised host. American Journal of Medicine 80 (Suppl. 6B), 149-155. Govan, J. R. W. & Gillies, R. R. (1969). Further studies in the pyocine typing of Pseudomonas pyocyanea. Journal of Medical Microbiology 2, 17-25. Joynson, D. H. M. (1978). Bowls and bacteria. Journal of Hygiene 80, 423-425. Kreger, A. S. (1983). Pathogenesis of Pseudomonas aeruginosa ocular disease. Reviews of Infectious Diseases 5 (Suppl. S), 931-934. Rosenhoff, S., Wolf, M. L. & Chabner, B. A. (1974). Pseudomonas blepharoconjunctivitis: a complication of combination chemotherapy. Archives of Ophthalmology 91, 490491. Schimpff, S. C., Young, V. M., Greene, W. H., Vermeulen, G. D., Moody, M. S. & Wiernik, P. H. (1972). Origin of infection in nonlymphocytic leukemia. Annals of Internal Medicine 77, 707-714. Van der Meer, J. W. M., Alleman, M. & Boekhart, M. (1979). Infectious episodes in severely neutropenic patients. Infection 7, 171-175. Vogelman, B. & Craig, W. A. (1986). Kinetics of antimicrobial activity. Journal of Pediatrics 108, 835-840. Weiss, I. S. (1979). Pseudomonas orbital cellulitis. American Journal of Ophthalmology 87, 368-370.