- Email: [email protected]
Pseudoepidemic of mycobacterium fortuitum in bone marrow cultures
Jennifer Hoy, M.B.B.S. Kenneth Rolston, M.D. Roy L. Hopfer, Ph.D. Houston,
Texas
Nosocomial infections can produce significant morbidity and mortality. Nosocomial pseudoepidemics (defined as real clustering of false infections or artifactual clustering of real infections)’ can theoretically produce significant morbidity in patients when such patients receive unnecessary medication. Over a 20-year period, from 1956 to 1975, the Center for Disease Control investigated 181 nosocomial epidemics. Of these 11% were actual pseudoepidemics; more than half of these pseudoepidemits were traced to errors in collection, handling, or processing of specimens.’ We present an investigation of a pseudoepidemic of Mycobacterium fortuitum infections in patients with cancer, who are prone to unusual opportunistic infections.
Three patients with acute myeloid leukemia underwent autologous bone marrow transplantation on Feb. 24, March 4, and March 8, 1985, respectively. They had routine bone marrow aspiration performed on March 12, 1985. Two of the three patients were receiving broadspectrum antibiotics for fever of unknown origin associated with neutropenia. The third patient had no fever and was well. The three bone marrow specimens had negative Ziehl-Neelsen From the Section of Infectious Diseases, Department Specialties, the University of Texas M D Anderson and Tumor Institute. Reprint requests: Kenneth (Box 47), M. D Anderson Houston, TX 77030.
of Medical Hospital
Rolston, M.D., Infectious Diseases Hospital, 1515 Holcombe Blvd.,
smears, but yielded M. fortuitum 7 to 14 days later. None of the patients had evidence of tissue invasion with M. fortuitum. Only one patient received treatment for possible M. fortuiturn infection until a second bone marrow aspirate culture was sterile. M. fortuitum was not isolated from repeat bone marrow aspirates taken from all three patients within 7 to 14 days of the initial positive culture. The fourth patient was admitted in April 1985, with recurrence of adenocarcinoma of the lung and for investigation of episodes of fever and arthritis. He underwent an extensive workup, including a bone marrow aspiration and biopsy, specimens from which were sent for bacterial, viral, fungal, and mycobacterial stains and cultures. Again, the Ziehl-Neelsen smear was negative, and an acid-fast organism, subsequently identified as M. fortuitum, was isolated 1 week later. He received three antituberculous drugs for 6 weeks. Subsequently, it was concluded that his fever and arthritis were caused by systemic lupus erythematosus, and he responded to steroid administration.
The first three bone marrow specimens that subsequently grew M. fortuitum had been aspirated on the same day (March 12, 19&S). All three patients were located on the third floor of the hospital. Six other bone marrow aspirates were obtained on March 12. These six were from other floors of the hospital, and ail had negative cultures and smears for acid-fast bacilli. Review of the records in the acid-fast bacillus lab-
Volume December
15 Number
6
1967
oratory showed that the nine bone marrow specimens were all processed at the same time and the three positive specimens were clustered together. Transfer (carryover) from one specimen to the next was possible but seemed unlikely because bone marrow specimens are not processed (decontaminated) or centrifuged before inoculation of media. Diluents and buffers used in the acid-fast bacillus laboratory were cultured for M. fortuitum and discarded, and were subsequently negative for growth. Technologists were reminded to use extreme care in processing future specimens. In our hospital, bone marrow aspirations and biopsies are performed by a team of four nurses. We observed the technique of bone marrow sampling as done by these nurses and could seen no obvious source for the contamination. Because no source of contamination was found, we decided to keep a close watch on culture results coming from the acid-fast bacillus laboratory. The problem seemed resolved until the fourth patient’s bone marrow aspirate yielded M. fortuitum on April 23, 1985. The possibility of laboratory contamination seemed even less likely because only one out of 27 specimens (six bone marrow aspirates) processed the same day grew M. fortuitum. Inasmuch as this fourth patient was also admitted to the third floor, we reevaluated what might be different about specimens taken from patients located on this floor. We discovered that patients undergoing bone marrow transplantation receive nursing care on the third floor and have bone marrow aspirates taken that are routinely sent for viral cultures. Patients located on other floors of the hospital who undergo bone marrow aspiration procedures rarely have viral cultures sent unless infection is strongly suspected. If a viral culture is requested (which happens most often on the third floor), the syringe containing the bone marrow aspirate, with its needle and cap attached, is plunged into ice for transport to the microbiology laboratory. If, however, viral cultures are not requested, the bone marrow specimens are not transported on ice. The ice used to transport specimens for viral culture is available from ice-making machines located on each floor of the hospital. Samples of
Pseudoepidemic of Mycobacterium
fortuitum
269
ice were collected from the ice machines on the third floor and from five other floors of the hospital. The ice was allowed to melt and was cultured for acid-fast bacilli. All direct ZiehlNeelsen stains were negative. Melted unconcentrated ice from the third floor grew M. fortuitum after 7 days incubation. Similar melted ice from all the other floors did not grow acidfast bacilli. Centrifuged ice specimens (approximately 50 ml) were positive for M. fortuitum from the third, eighth, tenth, and eleventh floors. Concentrated ice specimens from the fifth and ninth floors did not grow mycobacteria. DISCUSSION
Rapidly growing mycobacteria are environmental mycobacteria found in soil and water. However, only M. fortuitum and Mycobacterium chelonae are recognized as human pathogens’ These organisms may colonize the respiratory mucosa without causing pulmonary disease.3 In recent years, M. fort&urn and M. chelonae have been increasingly recognized as significant human pathogens. They have been documented as causing primary cutaneous infections (usually associated with trauma),4 pulmonary infections,3 disseminated disease,4 and nosocomial or iatrogenic infections. The nosocomial or iatrogenic infections include injection abscesses,* sternal wound infections after open-heart surgery,‘-’ prosthetic valve endocarditis,4,s wound infection after augmentation mammoplasty,’ and peritonitis in patients undergoing chronic ambulatory peritoneal dialysis.” Patients receiving bone marrow transplants are prone to infection in the immediate posttransplantation period while they have neutropenia. They remain susceptible because of immunosuppressive therapy used to prevent graft rejection. When a fever of unknown origin develops in these patients, bone marrow specimens are sent for smears and cultures to exclude possible viral, bacterial, and fungal etimay receive ologic agents. These patients unnecessary chemotherapy when unusual organisms (e.g., rapidly growing mycobacteria) are cultured from normally sterile sources, if the possibility of contamination is not ruled out. Not only are the patients at risk of adverse
Ameiican
270
Hoy, Rolston,
and Hopfer
side effects of the unnecessary antibiotic therapy, but there may be a further delay in investigating the actual cause of the fever. This could be very detrimental to a patient with neutropenia. Contamination must always be suspected when a cluster of unexpected organisms is isolated from normally sterile body sites, especially when the patient’s clinical condition is inconsistent (as was true with our patients) with the laboratory findings. However, the source of contamination related to pseudoepidemics is often not established’~1’~‘2 for a variety of reasons, including delay in recognizing the outbreak because of culture incubation times and the use of, discarding of, or outdating of the possible source of contamination (such as buffers and diluents). Nevertheless, the problem must always be investigated, and investigation does occasionally, as in this instance, lead to a solution. The pseudo-outbreak reported here was easy to suspect because (1) M. forttlittlm is an infrequent isolate, (2) all specimens from which M. fort&urn was isolated were bone marrow aspirates, (3) all positive specimens were collected from the same hospital floor, and (4) the initial specimens were all collected on the same day. Obfuscating the issue was that all the positive specimens were processed in sequence in the mycology laboratory whereas six others processed on the same day were negative. This strongly suggested carryover from the first positive specimen in the sequence. On the other hand, the six negative cultures reduced the likelihood that any buffers or diluents in the laboratory were contaminated. Subsequent negative cultures of these materials served to rule out such contamination. Another possible source of contamination was the equipment used on the third floor to perform bone marrow aspiration procedures. This was a real concern because it implied that the M. fortuitum could have been injected into the bone marrow during the procedure. Immediate investigation revealed that the bone marrow team uses a special cart to carry all their equipment. This information suggested another
INFECTION
Jourw
oi
CONTRO:
source because the same cart was used on all floors. As mentioned, we did observe the bone marrow team while they performed an aspiration procedure to determine whether there was any break in aseptic technique. None was observed. The possible role of contaminated ice was recognized after questioning of the bone marrow team revealed that there were standing orders for viral cultures on bone marrow specimens of transplant recipients and that these specimens were always transported on ice whereas speeimens from other patients were not. That the third floor was the area where the cluster occurred was probably a result of two factors: (,l) patients undergoing bone marrow transplantation were transferred to this floor after marrow recovery (they were initially placed in a protected, laminar-airflow environment) and (2) the ice collected from this nursing station had a greater number of M. fovtuitum organisms present as judged by the semiquantitative results of the ice cultures. All bone marrow specimens for viral culture are now sent to the microbiology laboratory in screw-top vials containing viral transport medium, and housekeeping staff members clean the ice machines daily. After institution of these measures, there have not been any further positive cultures despite that 10 months later M. fortuitum was still cultured from the ice machines on the third, eighth, tenth, and eleventh floors. ffefemnces 1. Weinstein RA, Stamm WE. Pseudoepidemics in hospital. Lancet 1977;2:862-4. 2. Hand WL, Sanford JP. Mycobacterium fbrtuitum--a human pathogen. Ann Intern Med 1970:73:971-7. 3. Rolston KVI, Jones PG, Fainstein V, Bodey GP. Pulmonary disease caused by rapidly growing mycobacteria in patients with cancer. Chest 1985;87:503-6. 4. Wallace RJ, Swenson JM, Silcox VA, Good RC, Tschen JA, Stone MS. Spectrum of disease due to rapidly growing mycobacteria. Rev Infect Dis 1983;5:657-79. 5. Hoffman PC, Fraser DW, Robicsek F, O’Bar PR, Mauney CV. Two outbreaks of sternal wound infection due to organisms of the Mgcobacterium fordturn complex. J Infect Dis 1981;143:533-42. 6. Kuritsky JN, Bullen MG, Broome CV, Sdcox VA, Good RC, Wallace RJ. Sternal wound infections and endo-
Volume
15 Number
December
6
Pseudoepidemic of Mycobacterium
1967
to organisms of the Mycobacterium fortuiAnn Intern Med 1983;98:938-9. 7. Robicsek F, Daugherty HK, Cook JW, et al. Mycobacterium fortuitum epidemics after open-heart surgery. J Thorac Cardiovasc Surg 1978;75:91-6. 8. Repath F, Seabury JH, Sanders CV, Domer J. Prosthetic valve endocarditis due to Mycobacterium chelonei. South Med J 1976;69:1244-6. 9. Clegg HW, Foster MT, Sanders WE, Baine WB. Infection due to organisms of the Mycobacterium fortuitum complex after augmentation mammoplasty: clinical and epidemiological features. J Infect Dis 1983;147: 427-33. carditis
due
turn complex.
fortuitum
10. Band JD, Ward JI, Fraser DW, et al. Peritonitis due to a Mycobacterium chelonei-like organism associated with chronic peritoneal dialysis. J Infect Dis 1982;145: 9-17. 11. Kusek JW. Nosocomial pseudoepidemics and pseudoinfections: an increasing problem. AM J INFECT CONTROL
1981;9:70-5.
12. Maki DG. Through a glass darkly. doepidemics and pseudobacteremias. 1980;140:26-8.
Bound volumes available
Nosocomial Arch Intern
to subscribers
Bound volumes of AMERICAN JOURNAL OF INFECTION CONTROL are available to subscribers (only) for the 1987 issues from the Publisher, at a cost of $24.00 ($30.00 international) for Vol. 15 (January-December). Shipping charges are included. Each bound volume contains a subject and author index. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C. V. Mosby Company, Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146 USA; phone 800-325-4177, ext. 351.
Subscriptions must be in force to qualify. of a regular journal subscription.
271
Bound volumes are not available
in place
pseuMed
Texas
Nosocomial infections can produce significant morbidity and mortality. Nosocomial pseudoepidemics (defined as real clustering of false infections or artifactual clustering of real infections)’ can theoretically produce significant morbidity in patients when such patients receive unnecessary medication. Over a 20-year period, from 1956 to 1975, the Center for Disease Control investigated 181 nosocomial epidemics. Of these 11% were actual pseudoepidemics; more than half of these pseudoepidemits were traced to errors in collection, handling, or processing of specimens.’ We present an investigation of a pseudoepidemic of Mycobacterium fortuitum infections in patients with cancer, who are prone to unusual opportunistic infections.
Three patients with acute myeloid leukemia underwent autologous bone marrow transplantation on Feb. 24, March 4, and March 8, 1985, respectively. They had routine bone marrow aspiration performed on March 12, 1985. Two of the three patients were receiving broadspectrum antibiotics for fever of unknown origin associated with neutropenia. The third patient had no fever and was well. The three bone marrow specimens had negative Ziehl-Neelsen From the Section of Infectious Diseases, Department Specialties, the University of Texas M D Anderson and Tumor Institute. Reprint requests: Kenneth (Box 47), M. D Anderson Houston, TX 77030.
of Medical Hospital
Rolston, M.D., Infectious Diseases Hospital, 1515 Holcombe Blvd.,
smears, but yielded M. fortuitum 7 to 14 days later. None of the patients had evidence of tissue invasion with M. fortuitum. Only one patient received treatment for possible M. fortuiturn infection until a second bone marrow aspirate culture was sterile. M. fortuitum was not isolated from repeat bone marrow aspirates taken from all three patients within 7 to 14 days of the initial positive culture. The fourth patient was admitted in April 1985, with recurrence of adenocarcinoma of the lung and for investigation of episodes of fever and arthritis. He underwent an extensive workup, including a bone marrow aspiration and biopsy, specimens from which were sent for bacterial, viral, fungal, and mycobacterial stains and cultures. Again, the Ziehl-Neelsen smear was negative, and an acid-fast organism, subsequently identified as M. fortuitum, was isolated 1 week later. He received three antituberculous drugs for 6 weeks. Subsequently, it was concluded that his fever and arthritis were caused by systemic lupus erythematosus, and he responded to steroid administration.
The first three bone marrow specimens that subsequently grew M. fortuitum had been aspirated on the same day (March 12, 19&S). All three patients were located on the third floor of the hospital. Six other bone marrow aspirates were obtained on March 12. These six were from other floors of the hospital, and ail had negative cultures and smears for acid-fast bacilli. Review of the records in the acid-fast bacillus lab-
Volume December
15 Number
6
1967
oratory showed that the nine bone marrow specimens were all processed at the same time and the three positive specimens were clustered together. Transfer (carryover) from one specimen to the next was possible but seemed unlikely because bone marrow specimens are not processed (decontaminated) or centrifuged before inoculation of media. Diluents and buffers used in the acid-fast bacillus laboratory were cultured for M. fortuitum and discarded, and were subsequently negative for growth. Technologists were reminded to use extreme care in processing future specimens. In our hospital, bone marrow aspirations and biopsies are performed by a team of four nurses. We observed the technique of bone marrow sampling as done by these nurses and could seen no obvious source for the contamination. Because no source of contamination was found, we decided to keep a close watch on culture results coming from the acid-fast bacillus laboratory. The problem seemed resolved until the fourth patient’s bone marrow aspirate yielded M. fortuitum on April 23, 1985. The possibility of laboratory contamination seemed even less likely because only one out of 27 specimens (six bone marrow aspirates) processed the same day grew M. fortuitum. Inasmuch as this fourth patient was also admitted to the third floor, we reevaluated what might be different about specimens taken from patients located on this floor. We discovered that patients undergoing bone marrow transplantation receive nursing care on the third floor and have bone marrow aspirates taken that are routinely sent for viral cultures. Patients located on other floors of the hospital who undergo bone marrow aspiration procedures rarely have viral cultures sent unless infection is strongly suspected. If a viral culture is requested (which happens most often on the third floor), the syringe containing the bone marrow aspirate, with its needle and cap attached, is plunged into ice for transport to the microbiology laboratory. If, however, viral cultures are not requested, the bone marrow specimens are not transported on ice. The ice used to transport specimens for viral culture is available from ice-making machines located on each floor of the hospital. Samples of
Pseudoepidemic of Mycobacterium
fortuitum
269
ice were collected from the ice machines on the third floor and from five other floors of the hospital. The ice was allowed to melt and was cultured for acid-fast bacilli. All direct ZiehlNeelsen stains were negative. Melted unconcentrated ice from the third floor grew M. fortuitum after 7 days incubation. Similar melted ice from all the other floors did not grow acidfast bacilli. Centrifuged ice specimens (approximately 50 ml) were positive for M. fortuitum from the third, eighth, tenth, and eleventh floors. Concentrated ice specimens from the fifth and ninth floors did not grow mycobacteria. DISCUSSION
Rapidly growing mycobacteria are environmental mycobacteria found in soil and water. However, only M. fortuitum and Mycobacterium chelonae are recognized as human pathogens’ These organisms may colonize the respiratory mucosa without causing pulmonary disease.3 In recent years, M. fort&urn and M. chelonae have been increasingly recognized as significant human pathogens. They have been documented as causing primary cutaneous infections (usually associated with trauma),4 pulmonary infections,3 disseminated disease,4 and nosocomial or iatrogenic infections. The nosocomial or iatrogenic infections include injection abscesses,* sternal wound infections after open-heart surgery,‘-’ prosthetic valve endocarditis,4,s wound infection after augmentation mammoplasty,’ and peritonitis in patients undergoing chronic ambulatory peritoneal dialysis.” Patients receiving bone marrow transplants are prone to infection in the immediate posttransplantation period while they have neutropenia. They remain susceptible because of immunosuppressive therapy used to prevent graft rejection. When a fever of unknown origin develops in these patients, bone marrow specimens are sent for smears and cultures to exclude possible viral, bacterial, and fungal etimay receive ologic agents. These patients unnecessary chemotherapy when unusual organisms (e.g., rapidly growing mycobacteria) are cultured from normally sterile sources, if the possibility of contamination is not ruled out. Not only are the patients at risk of adverse
Ameiican
270
Hoy, Rolston,
and Hopfer
side effects of the unnecessary antibiotic therapy, but there may be a further delay in investigating the actual cause of the fever. This could be very detrimental to a patient with neutropenia. Contamination must always be suspected when a cluster of unexpected organisms is isolated from normally sterile body sites, especially when the patient’s clinical condition is inconsistent (as was true with our patients) with the laboratory findings. However, the source of contamination related to pseudoepidemics is often not established’~1’~‘2 for a variety of reasons, including delay in recognizing the outbreak because of culture incubation times and the use of, discarding of, or outdating of the possible source of contamination (such as buffers and diluents). Nevertheless, the problem must always be investigated, and investigation does occasionally, as in this instance, lead to a solution. The pseudo-outbreak reported here was easy to suspect because (1) M. forttlittlm is an infrequent isolate, (2) all specimens from which M. fort&urn was isolated were bone marrow aspirates, (3) all positive specimens were collected from the same hospital floor, and (4) the initial specimens were all collected on the same day. Obfuscating the issue was that all the positive specimens were processed in sequence in the mycology laboratory whereas six others processed on the same day were negative. This strongly suggested carryover from the first positive specimen in the sequence. On the other hand, the six negative cultures reduced the likelihood that any buffers or diluents in the laboratory were contaminated. Subsequent negative cultures of these materials served to rule out such contamination. Another possible source of contamination was the equipment used on the third floor to perform bone marrow aspiration procedures. This was a real concern because it implied that the M. fortuitum could have been injected into the bone marrow during the procedure. Immediate investigation revealed that the bone marrow team uses a special cart to carry all their equipment. This information suggested another
INFECTION
Jourw
oi
CONTRO:
source because the same cart was used on all floors. As mentioned, we did observe the bone marrow team while they performed an aspiration procedure to determine whether there was any break in aseptic technique. None was observed. The possible role of contaminated ice was recognized after questioning of the bone marrow team revealed that there were standing orders for viral cultures on bone marrow specimens of transplant recipients and that these specimens were always transported on ice whereas speeimens from other patients were not. That the third floor was the area where the cluster occurred was probably a result of two factors: (,l) patients undergoing bone marrow transplantation were transferred to this floor after marrow recovery (they were initially placed in a protected, laminar-airflow environment) and (2) the ice collected from this nursing station had a greater number of M. fovtuitum organisms present as judged by the semiquantitative results of the ice cultures. All bone marrow specimens for viral culture are now sent to the microbiology laboratory in screw-top vials containing viral transport medium, and housekeeping staff members clean the ice machines daily. After institution of these measures, there have not been any further positive cultures despite that 10 months later M. fortuitum was still cultured from the ice machines on the third, eighth, tenth, and eleventh floors. ffefemnces 1. Weinstein RA, Stamm WE. Pseudoepidemics in hospital. Lancet 1977;2:862-4. 2. Hand WL, Sanford JP. Mycobacterium fbrtuitum--a human pathogen. Ann Intern Med 1970:73:971-7. 3. Rolston KVI, Jones PG, Fainstein V, Bodey GP. Pulmonary disease caused by rapidly growing mycobacteria in patients with cancer. Chest 1985;87:503-6. 4. Wallace RJ, Swenson JM, Silcox VA, Good RC, Tschen JA, Stone MS. Spectrum of disease due to rapidly growing mycobacteria. Rev Infect Dis 1983;5:657-79. 5. Hoffman PC, Fraser DW, Robicsek F, O’Bar PR, Mauney CV. Two outbreaks of sternal wound infection due to organisms of the Mgcobacterium fordturn complex. J Infect Dis 1981;143:533-42. 6. Kuritsky JN, Bullen MG, Broome CV, Sdcox VA, Good RC, Wallace RJ. Sternal wound infections and endo-
Volume
15 Number
December
6
Pseudoepidemic of Mycobacterium
1967
to organisms of the Mycobacterium fortuiAnn Intern Med 1983;98:938-9. 7. Robicsek F, Daugherty HK, Cook JW, et al. Mycobacterium fortuitum epidemics after open-heart surgery. J Thorac Cardiovasc Surg 1978;75:91-6. 8. Repath F, Seabury JH, Sanders CV, Domer J. Prosthetic valve endocarditis due to Mycobacterium chelonei. South Med J 1976;69:1244-6. 9. Clegg HW, Foster MT, Sanders WE, Baine WB. Infection due to organisms of the Mycobacterium fortuitum complex after augmentation mammoplasty: clinical and epidemiological features. J Infect Dis 1983;147: 427-33. carditis
due
turn complex.
fortuitum
10. Band JD, Ward JI, Fraser DW, et al. Peritonitis due to a Mycobacterium chelonei-like organism associated with chronic peritoneal dialysis. J Infect Dis 1982;145: 9-17. 11. Kusek JW. Nosocomial pseudoepidemics and pseudoinfections: an increasing problem. AM J INFECT CONTROL
1981;9:70-5.
12. Maki DG. Through a glass darkly. doepidemics and pseudobacteremias. 1980;140:26-8.
Bound volumes available
Nosocomial Arch Intern
to subscribers
Bound volumes of AMERICAN JOURNAL OF INFECTION CONTROL are available to subscribers (only) for the 1987 issues from the Publisher, at a cost of $24.00 ($30.00 international) for Vol. 15 (January-December). Shipping charges are included. Each bound volume contains a subject and author index. The binding is durable buckram with the journal name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C. V. Mosby Company, Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146 USA; phone 800-325-4177, ext. 351.
Subscriptions must be in force to qualify. of a regular journal subscription.
271
Bound volumes are not available
in place
pseuMed