Outbreak of Mycobacterium chelon

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					Outbreak of Mycobacterium chelonae
Infection Associated With Use
of Jet Injectors
Jay D. Wenger, MD; John S. Spika, MD; Ronald W. Smithwick, MS; Vickie Pryor, RN, MPH; David W. Dodson, MD;
G. Alexander Carden, MD; Karl C. Klontz, MD, MPH

Between January 1 and May 15, 1988, foot infections due to Mycobacterium                                  February 22 and April 30, 1988. Within
chelonae subspecies abscessus were diagnosed in eight persons who had                                     2 weeks of podiatric procedures per¬
                                                                                                          formed in office A (one of two offices in
undergone invasive procedures at a podiatry office. A cohort study was per-                               which a podiatrist treated patients), pa¬
formed to evaluate risk factors for disease. Persons who underwent procedures
                                                                                                          tients   complained   of   pain and   redness
before 10:30 AM were more likely to have developed infection than those with
                                                                                                          (often with a blister), followed by drain¬
procedures after that time (relative risk, 5.6). In addition, procedures involving                        age near the procedure site. All patients
any of the second through fourth toes were more likely to have resulted in                                were afebrile, but evaluation of the af¬
infection than procedures involving only the first and/or fifth toes (relative risk,                      fected extremity revealed tender, ery-
4.4). Persons with 0, 1, or 2 risk factors had attack rates of 5%, 14%, and 60%,                          thematous, and swollen        areas   close   or
respectively. Mycobacterium chelonae subspecies abscessus organisms of the                                slightly distal to the procedure or injec¬
same antimicrobial resistance pattern as the patients' strains were cultured from                         tion site. Incision and drainage of the
distilled water in a reusable, nonsterilized container. A jet injector used to                            lesions yielded scanty amounts of sero-
administer lidocaine was held between procedures in a mixture of the distilled                            sanguineous fluid but little purulent ma¬
water and a disinfectant as recommended by the manufacturer. Inoculation of                               terial. Three patients with osteomyeli¬
                                                                                                          tis had prolonged intravenous antibiotic
patients with mycobacteria by the jet injector may have only occurred early in the
day due to slow killing of the bacteria by the disinfectant. The outbreak empha-                          therapy and underwent bony débride-
                                                                                                          ment. The index case required amputa¬
sizes the pathogenicity of this water-associated organism and the need for high\x=req-\                   tion of the distal
level disinfection of jet injectors.                                                                                           phalanx of the fourth
                                                                                                          toe. The lesions resolved over a period
                                                                               (JAMA. 1990;264:373-376)   of weeks to months during treatment
                                                                                                          with a variety of antimicrobial agents.
                                                                                                             Epidemiologie Investigation.—The
                                                                                                          investigation was begun after the podia¬
   MYCOBACTERIUM chelonae is                           a    pathogen and most commonly causes             trist discontinued procedures in office A
rapidly growing species found occasion¬                     soft-tissue infections, although osteo¬       following identification of the outbreak.
ally in soil, water, and sewage.12 The                      myelitis, keratitis, and disseminated         A procedure was defined as anything
organism is an opportunistic human                          disease have been reported.** Mycobac¬        done by the podiatrist resulting in
                                                            terium chelonae has recently been de¬         breaking the skin barrier (ie, an injec¬
   From the Division of Bacterial Diseases, Center for      scribed as a cause of epidemic disease        tion or incision). A definite case of
Infectious Diseases, Centers for Disease Control, Atlan-
ta, Ga (Drs Wenger and Spika and Mr Smithwick);
                                                            associated with specific medical or sur¬      M chelonae soft-tissue infection was de¬
Florida Department of Health and Rehabilitative Ser-        gical invasive procedures.712 We de¬          fined as a foot seen by the podiatrist in
vices, Palm Beach County Public Health Unit, West           scribe an outbreak of M chelonae soft-        either office between January 1 and
Palm Beach (Ms Pryor); and Preventive Health Ser-
vices, Florida Department of Health and Rehabilitative      tissue infections related to use of jet       May 31, 1988, in which symptoms of
Services, Tallahassee (Dr Klontz). Drs Dodson and Car-      injectors, in which an environmental          pain, redness, and drainage at or near
den are in private practice in West Palm Beach, Fla.        source of the pathogen was identified.        the site of a procedure were accompa¬
   Use of trade names is for identification only and does
not imply endorsement by the US Public Health Service
                                                            Patients and Methods
                                                                                                          nied by culture of acid-fast bacteria
or by the US Department of Health and Human                                                               from the wound. Procedures on differ¬
Services.                                                      Six patients hospitalized with M che¬
  Reprint requests to Meningitis and Special Patho-
                                                                                                          ent  days performed on a single patient
gens Branch, Division of Bacterial Diseases, Centers        lonae infection of the foot were reported     were   considered separate procedures.
for Disease Control, Atlanta, GA 30333 (Dr Wenger).         to one county public health unit between      A   probable case was defined as a foot

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from which no cultures were obtained
but that otherwise fit the case definition
and had symptoms that persisted for
more than 2 weeks after the procedure.
   The podiatrist and all nurses working
at either office were interviewed about
office practices during the study period.
All patient visits to office A between
January 1 and April 30,1988, were eval¬
uated by review of office visit logs and
patient charts. At office B, charts of all
patients who underwent operative pro¬
cedures were reviewed for results of
follow-up evaluations.
   Samples of all injectable materials,
disinfectant and cleansing solutions, tap
water, and bandaging material as well
as swabs of environmental surfaces and
operative instruments were collected
from both offices. Operating procedures
were observed at office B. Production
facilities of the distilled-water manufac¬
turer supplying office A were observed,
and water samples were obtained.
   Laboratory Investigation.—The 71
specimens submitted for mycobacterial
culture included individual samples or
mixed combinations of dexamethasone,            Fig 1 .—Number of patients who underwent surgical procedures each week in office A during the outbreak of
bupivacaine, lidocaine, sterile water,          Mycobacterium chelonae infection. The number of patients who became infected is shown in white; the
                                                number of patients who did not become infected is shown In gray. The arrow denotes the date procedures
isopropyl alcohol, Mada Sonic disinfec¬         were   discontinued in office A.
tant (a mixture of quaternary ammoni¬
um halide compounds plus the chelating
agent      ethy lenediaminetetraacetate,         solution before inoculation to media.                injections   of bupivacaine hydrochlo-
Mada Medical Products Inc, Carlstadt,            Swabs from surfaces thought to be con¬               ride-dexamethasone mixture only and a
NJ), carboys of distilled water from a           taminated with other bacteria were                   variety of operations (such as bunionec-
local supplier, tap water from various           treated as above, except that a 1% sodi¬             tomies, exostectomies, and osteoto¬
sites in the clinics, jugs of distilled water   um hydroxide solution replaced the                    mies), all followed by an injection of bu-
for daily needs that were filled from the        sterile water.                                       pivacaine-dexamethasone mixture. All
larger carboys, autoclave reservoir wa¬             Incubation and Identification.—                   persons who underwent a procedure
ter, and swabs of various surfaces in the        All inoculated media were incubated at               had their skin cleansed with povidone-
two clinics.                                    28°C. Isolates were identified by stan¬               iodine or alcohol and had skin wheals of
   Up to 50 mL of each liquid specimen          dard biochemical methods.u Minimal in¬                2% lidocaine hydrochloride solution
was placed in a sterile, 60-mL plastic          hibitory concentrations of antimicrobial              raised with a hand-held jet injector. For
disposable syringe and filtered under           drugs against all M chelonae subspecies               persons receiving bupivacaine-dexa-
plunger  pressure through a presteri-           abscessus isolates14 were determined.                 methasone injections without additional
lized 25-mm (0.4-p.m pore size) polycar¬            Survival of M chelonae in Disinfec¬               operative procedures, the injection
bonate membrane filter      (Nucleopore         tant Solution.—A working solution of                  mixture was given through a 21-gauge
Corp, Pleasanton, Calif). Organisms             Mada Sonic disinfectant was prepared                  needle into the deep and subcutaneous
were freed from the filter by shaking in        according to the manufacturer's in¬                   tissue. A sterile bandage was placed
phosphate buffer and inoculated to              structions, using water from the gallon               over the site. Persons receiving an inci¬
Lowenstein-Jensen slants. The suspen¬           jug known to contain M chelonae organ¬                sion had additional lidocaine injec¬
sion was inoculated to Dubos-Middle-            isms. At prescribed times (0,0.5,1,2,4,               tions. The operative procedure was
brook oleic acid albumin agar and to            24, and 48 hours), a 10-mL sample of the              then performed with new sterile scalpel
4 mL of modified 7H-9 broth. Swabs of           mixture was removed and handled as                    blades and autoclaved instruments. Af¬
environmental sites were each placed in         described above for liquid specimens.                 ter the procedure, deep injections
a 16 x 100-mm screwcap tube containing                                                                of bupivacaine-dexamethasone solution
10 mL of sterile distilled water, and the                                                             were given in and around the trauma¬
tube was shaken by hand for 10 to               Results                                               tized area. The site was bandaged, and
20 seconds. The swabs were then                    The podiatrist routinely spent 3 days              the patients were given a short course of
pressed against the side of the tube to         per week at office A and 2 days per week              an oral cephalosporin therapy. Al¬
express free fluid, and the suspension          at office B. Two nurses also rotated                  though the amount of bupivacaine-
was filtered through a polycarbonate            from office to office, while a third nurse            dexamethasone solution prepared for
membrane filter and handled as des¬             worked 3 days per week at office A only.              each type of operation was similar (2 to
cribed for the liquid specimens. Speci¬         Twenty to 40 patients per day were seen               3 mL), the precise amount used in each
mens thought to be contaminated with            at office A, with 0 to 8 procedures per¬              operation was not known. However,
bacteria other than mycobacterial spe¬          formed each day. Slightly fewer pa¬                   more solution was deposited in the easi¬
cies were treated for 10 minutes in 1%          tients were seen at office B.                         ly distensible tissue on either side of the
(final concentration) sodium hydroxide             Procedures.—Procedures included                    metatarsal bones than in the thin tissue

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                                                                                                              Fig 3.—Survival of the epidemic strain of Mycobac¬
                                                                                                              terium chelonae organisms in disinfectant solution.
                                                                                                              Distilled water from the gallon jug from which M
                                                                                                              chelonae organisms were isolated was used to di¬
                                                                                                              lute Mada Sonic disinfectant according to the manu¬
                                                                                                              facturer's instructions. Asterisks indicate the log of
                                                                                                              the number of colony-forming units recovered after
                                                                                                              the disinfectant was mixed.

                                                                                                              Association of Risk Factors* With Disease

                                                                                                                                                 No. of Risk Factors
Fig 2.—Attack rate (number of cases per number of separate procedures) of infection following surgical
procedures performed during each hour of the working day. The total number of procedures during each
period is indicated by n. Since no procedures were performed between noon and 1 pm, the 11:30-1:29 Interval   Outcome, No. of patients
                       1 -hour time                                                                             III
was   considered   a                  period.                                                                   Well                             20      18        4
                                                                                                                Attack rate, %                    5      14       60

                                                                                                                The risk factors were (1) procedure performed by
                                                                                                              10:30am and (2) procedure involving any of toes 2
on   the medial side of the first toe and the             between January 1 and April 15, 1988.               through 4.
 lateral side of the fifth toe.                           The mean time of follow-up was 2
     Procedures and supplies were similar                 months for patients in both offices.
 in most respects for both offices. Dis¬                     Risk Factors.—To identify risk fac¬
 tilled water was purchased from sepa¬                    tors for disease, we studied records for            factors(procedure before 10:30 am and
 rate suppliers and poured into gallon                    all patients who underwent invasive                 procedure including any of toes 2
jugs for daily use. Nurses routinely pre¬                 procedures in office A between January              through 4) further increased a person's
pared the disinfectant solution—in                        22, 1988 (the date of the first invasive            likelihood of infection (Table).
which the jet injector tip was immersed                   procedure associated with infection),                  Laboratory Results. —Eleven of 71
before and after use on each patient—                     and April 27, 1988 (when procedures                 samples submitted for culture were pos¬
using distilled water from the gallon                     were discontinued in office A). Fifty-six           itive for mycobacteria. Mycobacterium
jug. The solution was prepared fresh                      procedures were performed during this               chelonae subspecies abscessus organ¬
each morning at approximately 8 AM                        period. Age, sex, preoperative hemo¬                isms were isolated only from water in
and discarded that evening.                               globin level, preoperative serum glu¬               the gallon jug of distilled water (two
     A total of 726 patient visits to office A            cose concentration, and the type and                samples). Mycobacterium gordonae or¬
were recorded between January 1 and                       duration of operation were not associ¬              ganisms were also isolated from the gal¬
April 30,1988. By the end of the investi¬                 ated with infection. However, when all              lon jug. Mycobacterium gordonae or¬
gation, 9 definite and 1 probable case of                 procedures for which site of procedure              ganisms grew in seven other positive
disease were detected among 8 pa¬                         was  known were compared, procedures                samples, and an orange-pigmented,
tients. In the following analysis, defi¬                  involving an inner toe (any of toes 2               slowly growing acid-fast organism that
nite and probable cases were combined.                    through 4) were more likely to result in            was  not further identified grew in two
Results are similar if the probable case                  infection than procedures involving                 other  samples. No cultures of speci¬
is deleted. The first procedure associ¬                   only an outer toe (toe 1 or 5,7 of 18 vs 3 of       mens from office B were positive for
ated with an infection was performed on                   34 procedures; relative risk, 4.4; 95%              M chelonae, including those from the
January 22,1988 (Fig 1), and the last on                  confidence interval, 1.3 to 15).                    gallon jug used to store distilled water.
April 15, 1988. In 2 cases, infection fol¬                   The time of the procedure was also a             Cultures of all samples (including dis¬
lowed a bupivacaine-dexamethasone in¬                     risk factor (Fig 2). Persons who under¬             tilled water from unopened containers)
jection without additional invasive pro¬                  went a procedure before 10:30 am were               from the distilled-water manufacturer
cedures. The incubation period ranged                     more likely to develop infection than               were negative for mycobacteria.
from 14 to 42 days, with a mean of 21                     those with procedures after that time                   The results of the investigation to de¬
days. No cases occurred in 46 patients                    (relative risk, 5.7; 95% confidence inter¬          termine the length of survival of M che¬
who underwent procedures at office B                      val, 1.3 to 24). The presence of both risk          lonae subspecies abscessus organisms

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in disinfectant are shown in Fig 3. The       were isolated from any sample of water                  3. Wolinsky E. Nontuberculous mycobacteria and
number of viable M chelonae subspecies        from the distilled-water producer. Al¬                  associated diseases. Am Rev Respir Dis. 1979;
abscessus colony-forming units was re¬        though M chelonae organisms were not                    4. Good RC. Opportunistic pathogens in the genus
duced by 98% after 4 hours. No viable         isolated from tap water in this investi¬                Mycobacterium. Annu Rev Microbiol. 1985;39:
mycobacteria could be isolated after 24       gation, they can be recovered from mu¬                  347-369.
                                                                                                      5. Wallace RJ, Swenson JM, Silvox VA, Bullen
or 48 hours.                                  nicipal and well-water samples.11219                    MG. Treatment of nonpulmonary infections due to
   Results of standard biochemical            Thus, although nursing personnel de¬                    Mycobacterium fortuitum and Mycobacterium
tests13 were compatible with descrip¬         nied rinsing the gallon jug with tap wa¬                chelonei on the basis of in vitro susceptibilities. J
tions of M chelonae subspecies absces¬        ter, the nearby sink (under which the                   Infect Dis. 1985;152:500-514.
                                                                                                      6. Woods GL, Washington JA II. Mycobacteria
sus for all isolates. The minimum inhibi¬     jug was stored) was a likely source for                 other than Mycobacterium tuberculosis: review of
tory concentrations for both environ¬         initial contamination.                                  microbiologic and clinical aspects. Rev Infect Dis.
mental and patient isolates were within           To our knowledge, this is the second                1987;9:275-294.
a twofold dilution of one another. The        outbreak of an infectious disease linked                7. Band JD, Ward JI, Fraser DW, et al. Peritonitis
                                                                                                      due to a Mycobacterium chelonei-like organism as-
minimum inhibitory concentration for          to jet injectors. Hepatitis B virus was                 sociated with intermittent chronic peritoneal dialy-
cefoxitin was 16 to 32 mg/L; for amika-       transferred from person to person                       sis. J Infect Dis. 1982;145:9-17.
cin sulfate, 16 mg/L; for ciprofloxacin       through subcutaneous jet injections in a                8. Mycobacterium chelonei infections following
hydrochloride, 8 to 16 mg/L; for rifam-       weight-loss clinic.20 Experimental stud¬                eye surgery: Texas. MMWR. 1983;32:591-598.
                                              ies in mice have demonstrated mouse-                    9. Kuritsky JN, Bullen MG, Broome CV, Silcox
pin, 8 to 16 mg/L; and for doxycycline                                                                NA, Good RC, Wallace RJ. Sternal wound infec-
hyclate, greater than 32 mg/L.                to-mouse transmission of lactate dehy-                  tions and endocarditis due to organisms of the My-

                                              drogenase virus during subcutaneous                     cobacterium fortuitum complex. Ann Intern Med.
                                              inoculation using jet injectors.21 Many                 1983;98:938-939.
                                                                                                      10. Bolan G, Reingold AL, Carson LA, et al. Infec-
   Although several outbreaks of injec¬       jet injections require touching the skin                tions with Mycobacterium chelonei in patients re-
tion-related M chelonae disease have           of each recipient with the tip of the in¬              ceiving dialysis and using processed hemodia-
been reported, a source of the organism        strument. Use of these instruments for                 lyzers. J Infect Dis. 1985;152:1013-1019.
            identified.15"18 We identified     subcutaneous or intramuscular injec¬                   11. Safranik TJ, Jarvis WR, Carson LA, et al.
was never
                                               tions in persons infected with hepatitis               Mycobacterium chelonae wound infections after
two risk factors for disease and isolated                                                             plastic surgery employing contaminated gentian
the organism from distilled water in a         B virus or human immunodeficiency vi¬                  violet skin-marking solution.     N   Engl J Med.
reusable gallon jug. A jet injector disin¬     rus can result in detectable viral mark¬               1987;317:197-201.
fectant solution diluted with water from       ers on the skin surface after injection.22             12. Lowry PW, Beck-Sague CM, Bland LA, et al.
                                               The World Health Organization has                      Mycobacterium chelonae infection among patients
this jug was the probable source of the                                                               receiving high-flux dialysis in a hemodialysis clinic
organism, which was transferred to the         suggested that use of jet injectors be                 in California. J Infect Dis. 1990;161:85-90.
patients by the jet injector.                  restricted to special circumstances until              13. Kent PT, Kubica GP. Public Health Mycobac-
    The reason for the increased risk of       the risk of transmission of infectious dis¬            teriology: A Guide for the Level III Laboratory.
                                               eases can be further clarified.23                      Atlanta, Ga: Centers for Disease Control; 1985.
disease associated with operations on                                                                 14. Swenson JM, Thornsberry C, Silcox VA. Rap-
the inner portion of the foot is not clear,       This outbreak of M chelonae infection               idly growing mycobacteria: testing of susceptibility
but it may be due to the different             demonstrates a different risk of jet in¬               to 34 antimicrobial agents by broth microdilution.
                                               jectors. Use of slowly acting mycobac-                 Antimicrob Agents Chemother. 1982;22:186-192.
amounts of bupivacaine-dexametha¬                                                                     15. Inman PM, Beck A, Brown AE, Stanford JL.
sone solution injected into intermeta-         tericidal disinfectant solutions led to the
                                                                                                      Outbreak of injection abscesses due to Mycobacte-
tarsal areas vs outer-toe tissues. De¬         transmission of M chelonae organisms.                  rium abscessus. Arch Dermatol. 1969;100:141-147.
creased local inflammatory responses in         Since such bacteria are often resistant                16. Borghans JGA, Stanford JL. Mycobacterium
                                               to many standard disinfectant agents,                  chelonei in abscesses after injection of diphtheria-
the intermetatarsal soft tissues may                                                                  pertussis-tetanus-polio  vaccine. Am Rev Respir
have resulted from higher concentra¬           use of a rapidly tuberculocidal disinfec¬
                                                                                                      Dis. 1973;107:1-8.
tions of the long-acting steroid in those      tant, eg, 2% alkaline glutaraldehyde, is               17. Pettini B, Hellstrand P, Ericksson M. Infection
areas. The microbiologie basis for the          appropriate. Such instruments should                  with Mycobacterium chelonei following injections.
association of disease with the time of         be bathed in effective disinfectant solu¬             Scand J Infect Dis. 1980;12:237-238.
                                               tions for at least 30 minutes between                  18. Jackson PG, Keen H. Nobel CT, Simmons NA.
the procedure was demonstrated by the                                                                 Injection abscesses due to Mycobacterium chelonei
laboratory studies. Patients were ex¬           use. Storing distilled water in single-               occurring in a diabetic patient. Tubercle. 1981;62:
posed to the contaminated distilled wa¬         use containers will also reduce the dan¬              277-279.
                                                ger of contamination.                                 19. Carson LA, Petersen NJ, Favero MS, Aguero
ter through the jet injector disinfectant                                                             SM. Growth characteristics of atypical mycobacte-
bath. Mycobacteria present in the dis¬            We thank Robert C. Good, PhD, George P. Ku-         ria in water and their comparative resistance to
tilled water-disinfectant solution were       bica, PhD, and Claire V. Broome, MD, for        con¬    disinfectants. Appl Environ Microbiol. 1978;36:
 killed over a period of several hours.       structive criticism of the manuscript; James 0. Kil-    839-846.
                                              burn, PhD, Vella A. Silcox, MS, Ray Butler, MS,         20. Hepatitis B associated in jet gun injection: Cali-
Thus, patients injected early in the day      and Charles L. Woodley, PhD, for assistance in the      fornia. MMWR. 1986;35:373-376.
 may have been exposed to a large inocu¬      laboratory evaluation of the mycobacterial isolates;    21. Brink PRG, Van Loon AM, Tromellen JEM,
 lum, while patients injected later were      and Janis Sexton for secretarial assistance.            Gribnau FWJ, Smale-Novakova IRO. Virus trans-
                                                                                                      mission by subcutaneous jet injection. J Med Mi-
 exposed to fewer or no mycobacteria. A        References                                             crobiol. 1985;20:393-397.
 combination of both factors—jet injec¬                                                               22. Zachoval R, Deinhardt F, Gurtler L, Eisen-
 tion (with a high mycobacterial inocu¬        1. Won Jin B, Saito H, Yoshi Z. Environmental          burg J, Korger G. Risk of virus transmission by jet
 lum) in the morningplus larger amounts        Mycobacteria in Korea, I: distribution of the organ-   injection. Lancet. 1988;9:189.
 of steroid injection—resulted in the          isms. Microbiol Immunol. 1984;28:667-677.              23. Global Advisory Group. Expanded programme
                                               2. Lowry PW, Jarvis WR, Oberle AD, et al. Myco-        on immunization. Weekly Epidemiol Rec. January
 greatest risk of developing disease.          bacterium chelonae causing otitis media in an ear-      16,1987;62:5-9.
     It is unclear how the gallon jug be¬      nose-and-throat practice. N Engl J Med. 1988;
 came contaminated. No mycobacteria            319:978-982.

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