Skin and Soft Tissue Infections Due to Rapidly Growing Mycobacteria Comparison of Clinical Features, Treatment, and Susceptibility

Home , Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum

STUDY Skin and Soft Tissue Infections Due to Rapidly Growing Mycobacteria Comparison of Clinical Features, Treatment, and Susceptibility

Daniel Z. Uslan, MD; Todd J. Kowalski, MD; Nancy L. Wengenack, PhD; Abinash Virk, MD; John W. Wilson, MD

Objective: To compare the demographics, clinical fea- more likely to be taking immunosuppressive medica- tures, susceptibility patterns, and treatment for skin and tions (60% vs 17%, P=.002) than patients with M fortui- soft tissue infections due to Mycobacterium fortuitum and tum. Mycobacterium fortuitum tended to manifest as a Mycobacterium chelonae or Mycobacterium abscessus. single lesion (89% vs 38%, PϽ.001), while most M chelonae or M abscessus manifested as multiple lesions (62% Design: Retrospective medical record review. vs 11%, PϽ.001). More patients with M fortuitum had a prior invasive surgical procedure at the infected site (56% Setting: Mayo Clinic, Rochester, Minn. vs 27%, P=.04). Patients with multiple lesions were more likely to be taking immunosuppressive medications than Patients: All patients seen at our institution with a posi- those with single lesions (67% vs 30%, P=.006). Seven tive culture for M chelonae, M abscessus,orM fortuitum patients failed treatment, several of whom were immu- from skin or soft tissue sources between January 1, 1987, nocompromised and had multiple comorbidities. and October 31, 2004. Conclusions: Skin and soft tissue infections due to rap- Main Outcome Measures: Patient demographics, clini- idly growing mycobacteria are associated with systemic cal characteristics, therapeutic data, microbiological data, comorbidities, including the use of immunosuppressive and outcomes. medications. There are significant differences in the demographic and clinical features of patients who acquire spe- Results: The medical records of 63 patients with skin cific organisms, including association with immunosup- or soft tissue infections due to rapidly growing myco- pression and surgical procedures. bacteria were reviewed. Patients with M chelonae or M abscessus were older (61.5 vs 45.9 years, PϽ.001) and Arch Dermatol. 2006;142:1287-1292

YCOBACTERIUM FORTUI- Although the spectrum and features of tum, Mycobacterium clinical disease due to M chelonae have chelonae, and Mycobac- been described,3 no reports have directly terium abscessus are compared the clinical features of skin and environmental myco- soft tissue infections due to M chelonae, Mbacteria that can cause chronic infections M abscessus, and M fortuitum,toour of the skin, soft tissues, and lungs. These or- knowledge. We retrospectively reviewed ganisms are characterized by rapid all patients with skin and soft tissue iso- growth on standard media and by lack of lates of rapidly growing mycobacteria at pigmentation.1 Clinical manifestations in- our institution to compare the demograph- clude localized abscess formation and ics, clinical features, susceptibility pat- 1,2 Author Affiliations: Division of chronic ulcers. Disseminated infections, terns, and treatment for M fortuitum and Infectious Diseases, Department especially in immunocompromised hosts, M chelonae or M abscessus. of Medicine (Drs Uslan, have been widely described.1,3,4 There are Kowalski, Virk, and Wilson), multiple reports of infection after trauma METHODS and Division of Clinical and surgical or other procedures, includ- Microbiology, Department of ing acupuncture,5 liposuction,6-8 silicone Laboratory Medicine and injection,9 breast implantation,10-12 intra- The medical records of all consecutive patients Pathology (Dr Wengenack), venous catheter use,13 dermatologic having clinical isolates of M chelonae, Mayo Clinic College of M abscessus, and M fortuitum from skin and soft surgery,14,15 pedicures,16-18 exposure to pros- Medicine, Rochester, Minn. 19 20 tissue seen at our institution between January 1, Dr Kowalski is now with the thetic material, pacemaker placement, 1987, and October 31, 2004, were reviewed ret- 21-25 Division of Infectious Disease, and subcutaneous injections. Pulmo- rospectively. All patients had given consent for Gundersen Lutheran Medical nary disease due to M fortuitum has been the use of their medical records for research pur- Center, LaCrosse, Wis. described following hot tub use.26 poses, and our institutional review board ap-

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 RESULTS Table 1. Demographics of 63 Patients With Definite Skin or Soft Tissue Infections by Organism* Seventy-six patients with skin or soft tissue infections due Mycobacterium chelonae or to rapidly growing mycobacteria were identified. Of these, Mycobacterium Mycobacterium 63 were classified as having definite infection and were fortuitum abscessus P included in the analysis. Clinical history was available Demographic (n = 18) (n = 45) Value for all patients. Susceptibility data were reviewed when Age, mean ± SD, y 45.9 ± 14.3 61.5 ± 13.6 Ͻ.001 available; given the 17-year interval, not all isolates had Female sex 10 (55.6) 25 (55.6) Ͼ.99 been tested against all antimicrobials in the current CLSI Current smoker 3 (16.7) 2 (4.4) .14 guidelines. Any of the following systemic 3 (16.7) 25 (55.6) .006 The patients included 35 women (56%) and 28 men comorbidities Diabetes mellitus 3 (16.7) 12 (26.7) .52 (44%), with a median age of 60 years (age range, 19-88 Malignant neoplasm 0 5 (11.1) .31 years). Patients came from 12 different states, with most Connective tissue disease 0 12 (26.7) .01 from Minnesota (29 patients), Wisconsin (7 patients), End-stage renal disease 1 (5.6) 7 (15.6) .4 Iowa (4 patients), and South Dakota (3 patients), which Congestive heart failure 1 (5.6) 3 (6.7) Ͼ.99 reflects the general patient population at our institu- Organ transplant 1 (5.6) 9 (20.0) .26 tion. Five patients (8%) were current smokers, and 6 pa- Kidney 1 (5.6) 6 (13.3) Liver 0 1 (2.2) tients (10%) were former smokers. In view of the retro- Pancreas 0 3 (6.7) spective nature of the study design and the lack of specific Lung 0 1 (2.2) information available in the medical records, no consis- Heart 0 1 (2.2) tent exposure, occupational, or avocational history (eg, Taking immunosuppressive 3 (16.7) 27 (60.0) .002 hot tub exposure) could be identified that might repre- medications sent risk factors for acquisition of these organisms. Prednisone, Ͼ5 mg 3 (16.7) 24 (53.3) .01 Others 2 (11) 16 (35.6) .06 Seven cultures (11%) were obtained via superficial Prior invasive procedure at 10 (55.6) 12 (26.7) .04 swab of a lesion, 34 (55%) via biopsy of a lesion, and 21 site of infection† (34%) at the time of surgical debridement or resection. Prior trauma at site of 3 (16.7) 3 (6.7) .34 The method of culture was unavailable for 1 patient. infection Smears for acid-fast bacilli were performed in 50 patients; 24 (48%) were positive for organisms. Sixteen cul- *Data are given as number (percentage) unless otherwise indicated. †Includes injection, aspiration, biopsy, or surgical procedures. tures (25%) yielded other bacteria in addition to rapidly growing mycobacteria, including coagulase-negative staphylococci, Staphylococcus aureus, and gram- negative organisms (Klebsiella species, Escherichia coli, proved the study. Information was collected regarding demo- and Proteus species). No patients’ cultures grew mul- graphics, immune status (including the use of immunosuppressive tiple different species of mycobacteria. Skin specimens medications), infection characteristics, site and clinical descrip- from 40 patients had been sent for pathological exami- tion of the lesions, antimicrobial therapy, surgical procedures, and outcome. Definite infection was defined as culture positivity in nation; granulomatous inflammation was observed in 21 the presence of a compatible clinical syndrome, such as chronic patients (53%). ulcers, wound drainage, or abscess. Patients with isolated single Demographics of the 63 patients by organism (M for- colonies in their cultures, in the absence of a compatible clinical tuitum or M chelonae or M abscessus) are given in Table 1. syndrome, were excluded from the analysis. There were 18 M fortuitum infections (29%) and 45 Organisms were identified by our laboratory as rapidly grow- M chelonae or M abscessus infections (71%). There were ing mycobacteria by standard criteria that included growth rate, significant differences noted between patients with Mfor- morphologic structure, mycolic acid analysis, and biochemi- 27 tuitum and M chelonae or M abscessus in their mean age cal test results (arylsulfatase and nitrate reduction). On No- (45.9 vs 61.5 years, PϽ.001), use of immunosuppres- vember 9, 1999, our microbiology laboratory began identify- sive medications at the time of infection (17% vs 60%, ing rapidly growing mycobacteria by 16S ribosomal RNA (rRNA) gene sequencing.28 Mycobacterium chelonae and M abscessus are P=.002), and history of an invasive procedure at the site indistinguishable by 16S rRNA gene sequencing and are re- of diagnosis (56% vs 27%, P=.04), as well as in the pres- ported together (as M chelonae or M abscessus) by most labo- ence of systemic comorbidities (including active malig- ratories, as well as herein. nancies, end-stage renal disease, congestive heart fail- Minimum inhibitory concentrations (MICs) of antimicro- ure, solid organ transplantation, and connective tissue bials were determined using serial 2-fold broth microdilution disease). None of the patients had human immunodefi- in cation-supplemented Mueller-Hinton broth at 30°C, as per ciency virus infection. The median time between the re- guidelines from the Clinical and Laboratory Standards Insti- 29 corded onset of symptoms and the culture of the lesion tute (CLSI). Minimum inhibitory concentration break points was 86 days (intraquartile range [IQR], 38.5-202.5 days). from the CLSI for interpretive criteria for rapidly growing my- There was no difference in the duration of symptoms be- cobacteria were used. Data were analyzed using JMP software (version 5.1.2; SAS fore diagnosis by organism, systemic comorbidities, or Institute, Cary, NC). Comparisons between categorical vari- immunosuppression status. Patients with multiple le- ables were analyzed using the Fisher exact test. Comparisons sions had a significantly longer duration of symptoms be- between continuous variables were analyzed using the Wil- fore diagnosis (median, 125 days [IQR, 52-342 days]) coxon rank sum test or independent t test, as appropriate. compared with patients with single lesions (median, 65

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 Table 2. Clinical Characteristics of 63 Patients Table 3. Factors Associated With Single vs Multiple With Definite Infection* Lesions*

Mycobacterium Single Multiple chelonae or Lesion Lesions P Mycobacterium Mycobacterium Factor (n= 33) (n= 30) Value fortuitum abscessus P Any of the following systemic 9 (27.3) 19 (63.3) .006 Characteristic (n = 18) (n = 45) Value comorbidities Single lesion 16 (88.9) 17 (37.8) Ͻ.001 Diabetes mellitus 5 (15.2) 10 (33.3) .14 Multiple lesions 2 (11.1) 28 (62.2) Ͻ.001 Malignant neoplasm 1 (3.0) 4 (13.3) .18 Lesion location Connective tissue disease 3 (9.1) 9 (30.0) .05 Chest or back 7 (38.9) 2 (4.4) .002 End-stage renal disease 3 (9.1) 5 (16.7) .46 Upper extremity 4 (22.2) 17 (37.8) .25 Congestive heart failure 1 (3.0) 3 (10.0) .34 Lower extremity 4 (22.2) 29 (64.4) .002 Organ transplant 4 (12.1) 6 (20.0) .50 Abdomen 3 (16.7) 0 .02 Current or former smoker 7 (21.2) 3 (10.0) .31 Head or neck 0 1 (2.2) Ͼ.99 Taking immunosuppressive 10 (30.3) 20 (66.7) .006 Maximum temperature, 37.3 (36-39) 37 (36-38.5) .19 medications median (range), °C† Prior invasive procedure at site 17 (51.5) 5 (16.7) .007 Leukocyte count, median 7.5 (6-17) 8.5 (3-36) .56 of infection (range), ϫ109/L‡ Prior trauma at site of infection 6 (18.2) 0 .03 Chronic wound or ulcer 7 (38.9) 25 (55.6) .26 Cellulitis 5 (27.8) 9 (20.0) .51 *Data are given as number (percentage) unless otherwise indicated. Drainage 9 (50.0) 21 (46.7) Ͼ.99 Pain at site 13 (72.2) 31 (68.9) .75 Erythema at site 11 (61.1) 28 (62.2) Ͼ.99 trauma (18% vs 0%, P=.03) or of an invasive surgical pro- *Data are given as number (percentage) unless otherwise indicated. †Mycobacterium fortuitum n = 16; M chelonae or M abscessus n = 42. cedure (52% vs 17%, P=.007) at the site of infection. ‡Mycobacterium fortuitum n = 14; M chelonae or M abscessus n = 40. Forty-five patients were treated with antimicrobial agents. Of the remaining 18 patients, 9 were treated with surgery alone. Fourteen patients received parenteral an- days [IQR, 17-165 days]) (P=.03). The median dura- timicrobial agents, with a median duration of 25 days tion of patient follow-up after diagnosis was 189 days (range, 6-158 days). Thirty-eight patients received oral (range, 4 to 5477 days [IQR, 93-831 days]). antimicrobial agents, with a median duration of 127 days The clinical features by organism are given in Table 2. (range, 9-891 days). Patients with multiple lesions were Thirty-three patients (52%) had a single lesion, and 30 treated for a median duration of 135 days (IQR, 38.5- patients (48%) had multiple lesions. Patients with M for- 230.75 days), while patients with single lesions were tuitum were more likely to initially be seen with single treated for a median duration of 181 days (IQR, 109.5- lesions than patients with M chelonae or M abscessus (89% 311.5 days), although this difference was not statisti- vs 38%, PϽ.001). Mycobacterium fortuitum was more fre- cally significant (P=.33). quently isolated from the chest or back (39% vs 4%, The 45 patients who were treated received a total of P=.002), while M chelonae or M abscessus was more fre- 102 courses of antimicrobial agents (with a course de- quently isolated from the lower extremities (64% vs 22%, fined as Ն7 days of receiving antimicrobial agents). A P=.002). There were no differences in leukocyte count, single antimicrobial was prescribed for 20 courses (20%). maximum temperature, or clinical description of skin find- Combination therapy (consisting of Ն2 antimicrobial ings between patients in the 2 groups. Given the retro- agents) was prescribed for 82 courses (80%). The most spective nature of the study and the reliance on medical frequently prescribed antimicrobial agents were macro- records for clinical information, detailed descriptions of lides (31 courses), fluoroquinolones (26 courses), lesions were often unavailable. Reported skin findings var- aminoglycosides (14 courses), cephalosporins (11 ied widely, including sinus tracts, nonhealing ulcers, sub- courses), and tetracyclines (9 courses). Antimicrobial cutaneous abscesses, subcutaneous fluctuant or firm nod- agents most frequently used for monotherapy included ules of varying size, and erythema in association with macrolides (12 courses) and fluoroquinolones (6 courses). ulcers or chronic drainage from prior surgical wounds. Thirty-seven patients (59%) underwent surgical pro- Specific descriptions of skin color were not typically docu- cedures. Patients with single lesions (76% [25/33]) were mented, although several patients’ nodules were de- more likely to undergo surgery than those with mul- scribed as “violaceous.” Only 2 patients (3%) had culture- tiple lesions (40% [12/30]) (P=.005). Surgical proce- proved pulmonary coinfection. dures were also more likely in patients without sys- Factors associated with single vs multiple lesions are temic comorbidities (71% [25/35]) than in patients with given in Table 3. Patients with multiple lesions were systemic comorbidities (43% [12/28] (P=.04). Surgery more likely than those with single lesions to be taking was not associated with other characteristics (organ- immunosuppressive medications (67% vs 30%, P=.006) ism, patient age, sex, or lesion location). or to have a systemic comorbidity (such as a malignant Given the short median duration of follow-up, we were neoplasm, diabetes mellitus, or connective tissue dis- unable to assess outcome by specific therapy or by demo- ease) (63% vs 27%, P=.006). Patients with single le- graphic factors. Treatment failure was defined as lack of sions were more likely to have a history of penetrating clinical improvement with therapy or relapse of the in-

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imi- Table 4. Susceptibilities of Isolates* penem, linezolid, sulfamethoxazole, and tobramycin. A few isolates were sent to referral laboratories for clofaz- Drug, Minimum Mycobacterium imine susceptibility testing; those results are not in- Inhibitory chelonae or Concentration, Mycobacterium Mycobacterium cluded given the absence of formal CLSI break points. µg/mL fortuitum abscessus Isolates of M fortuitum were universally susceptible to ami- Amikacin (n = 14) (n = 47) kacin. Isolates of M chelonae or M abscessus were uni- Susceptible, Յ16 14 (100.0) 30 (63.8) versally susceptible to clarithromycin but had varying re- Intermediate, 32 0 12 (25.5) sistance to amikacin (36% intermediate or resistant), Resistant, Ն64 0 5 (10.6) tobramycin (21% intermediate or resistant), and imi- Cefoxitin (n = 16) (n = 44) penem (94% intermediate or resistant). Acquired resis- Susceptible, Յ16 3 (18.8) 1 (2.3) tance to an antimicrobial agent, defined as a change in Intermediate, 32-64 5 (31.3) 4 (9.1) susceptibility category from the original culture, was not Resistant, Ն128 8 (50.0) 39 (88.6) Ciprofloxacin (n = 14) (n = 44) observed in strains isolated from any patient, regardless Susceptible, Յ1 12 (85.7) 1 (2.3) of his or her outcome. Intermediate, 2 0 5 (11.4) Resistant, Ն4 2 (14.3) 38 (86.4) Clarithromycin (n = 12) (n = 40) COMMENT Susceptible, Յ2 8 (67) 40 (100.0) Intermediate, 4 1 (8) 0 Resistant, Ն8 3 (25) 0 To our knowledge, these 63 patients with skin and soft Doxycycline (n = 12) (n = 66) tissue infection due to M fortuitum and M chelonae or Susceptible, Յ1 5 (41.7) 3 (8) M abscessus represent the largest case series directly com- Intermediate, 2-8 0 0 paring clinical characteristics of patients with rapidly Resistant, Ն16 7 (58.3) 36 (91.6) growing mycobacteria infection. These emerging infec- Imipenem (n = 10) (n = 33) Յ tions are increasingly important, especially because of their Susceptible, 4 7 (70.0) 3 (8.3) 2 Intermediate, 8 2 (20.0) 5 (15.2) association with surgical procedures and their ten- 3 Resistant, Ն16 1 (10.0) 26 (78.8) dency to disseminate in immunocompromised hosts. Di- Linezolid (n = 6) (n = 12) agnosis is often delayed, as mycobacterial cultures are not Susceptible, Յ9 5 (83.3) 6 (50.0) routinely performed on skin biopsy specimens or surgi- Intermediate, 16 1 (16.7) 5 (41.7) cal wound infections. The median time between the on- Resistant, Ն32 0 1 (8.3) set of symptoms and the microbiological diagnosis was Sulfamethoxazole (n = 15) (n = 43) 86 days. Therefore, a high index of suspicion is impera- Susceptible, Յ32 10 (66.7) 8 (18.6) Resistant, Ն64 5 (33.3) 35 (81.4) tive for the diagnosis to be made. Because our series in- Tobramycin (n = 11) (n = 33) cluded only culture-positive patients, it is possible that Susceptible, Յ4 1 (9.1) 26 (78.8) patients with clinically mild disease (who did not prompt Intermediate, 8 1 (9.1) 6 (18.2) a culture) or patients with lesions cultured elsewhere but Resistant, Ն16 9 (81.8) 1 (3.0) who were referred to our institution for management were missed. *Data are given as number (percentage). Susceptibility data are according to the 2003 Clinical and Laboratory Standards Institute standards.29 The clinical features and demographics in our study are similar to those of other case series of rapidly growing mycobacteria,2,3,30 although we found significant differences in age, systemic comorbidities, use of immunosuppres- fection during follow-up. Seven patients had docu- sive medications, and history of invasive procedures mented treatment failure. All patients with M chelonae between patients with M fortuitum and M chelonae or or M abscessus who failed treatment had multiple le- M abscessus. In general, the patients infected with sions or deep soft tissue infection. All were immuno- M chelonae or M abscessus were older and in poorer health, compromised, including 3 patients who were solid or- while the patients infected with M fortuitum were more gan transplant recipients. The 2 patients with M fortuitum likely to have experienced trauma or to have had a surgi- who failed treatment had infection at the site of prior sur- cal procedure at the site. This is also reflected in the sig- gical procedures (removal of skin cancer in one and ab- nificant difference between the organisms in the associa- dominoplasty in the other). Only 1 patient died of in- tion of multiple vs single lesions (11% of M fortuitum fection; this patient had disseminated disease, including infections had multiple lesions compared with 62% of 2 infected prosthetic joints, skin nodules, and lung in- M chelonae or M abscessus). Most patients with single lesions fection. The median time to failure was 154 days (range, had a history of trauma or a medical procedure at the sub- 20 to 1898 days). None of the patients who failed treat- sequent site of infection, similar to previous findings.2 Be- ment developed acquired antimicrobial resistance. cause the 63 patients in our study spanned a 17-year in- Susceptibility data (according to 2003 CLSI stan- terval and were evaluated retrospectively, details of physical dards29) and MICs for available isolates are given in examinations were obtained from the patients’ medical re- Table 4. Minimum inhibitory concentrations were records. Therefore, further clinical descriptions of skin le- viewed retrospectively and were available for different an- sions were limited to what had been recorded; specific de- timicrobials depending on the year the culture was per- tails such as lesion size, color, ulcer appearance, and formed. In general, MICs were determined for amikacin, presence of fluctuance were not typically available.

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 Optimal treatment of rapidly growing mycobacterial sions to undergo surgical debridement (76% vs 40%). Ex- infections remains poorly established. No study has com- tensive surgical debridement for widespread infection may pared different antimicrobial regimens, to our knowl- be technically challenging; however, patients with mul- edge. Current guidelines recommend susceptibility test- tiple lesions are more likely to be immunosuppressed and ing of all isolates, with use of empirical therapy suggested may be less likely to cure their infection with antimicro- until susceptibilities are known.1,31 A limitation of the bial agents alone. Combined medical and surgical therapy present study is the small number of isolates for which is likely to produce optimal results, in accord with cur- susceptibility testing results were available, especially for rent guidelines.1 In 2 reports of outbreaks of sternal wound some of the newer antimicrobial agents such as lin- infections due to M abscessus, approximately one third ezolid. Current guidelines recommend empirical amika- of the patients died of uncontrolled infection,41,42 sug- cin for treatment of M fortuitum; 100% of our isolates were gesting that aggressive therapy may be indicated for deep susceptible to this agent.1 In contrast to other published infection. Our study did not specifically address the is- studies,1,3,32-34 our M fortuitum isolates were not univer- sue of reduction of immunosuppression, but it is likely sally susceptible to ciprofloxacin (14% resistant), sulfa- that this may be beneficial, if tolerable by a patient rela- methoxazole (33% resistant), or imipenem (30% inter- tive to his or her underlying comorbidities. mediate or resistant). In contrast to previously published The prevalence of infections due to rapidly growing in vitro data,33 most of our isolates were intermediate or mycobacteria is unknown but is likely underestimated resistant to cefoxitin (81% of M fortuitum and 98% of given the wide range of presenting syndromes and the M chelonae or M abscessus). Clarithromycin appears to lack of knowledge about these organisms by many cli- be reliably active against M chelonae or M abscessus, al- nicians. Clinicians caring for patients with chronic skin though its activity against M fortuitum is less predict- or soft tissue infections, especially in immunosup- able.34 Our laboratory, as many others, uses 16S rRNA pressed patients or following a surgical procedure, should gene sequencing for the identification of rapidly grow- have a high index of suspicion for rapidly growing my- ing mycobacteria and does not distinguish between cobacterial disease. Further studies establishing the op- M chelonae and M abscessus. These organisms are known timal duration of therapy and comparing specific regi- to have diverging in vitro antimicrobial susceptibilities mens are warranted. to certain drugs, including tobramycin, amikacin, and cefoxitin. This may contribute to the broadened range of antimicrobial susceptibility data within our M chelonae Accepted for Publication: March 26, 2006. or M abscessus group, but it remains unclear whether fur- Correspondence: Daniel Z. Uslan, MD, Division of In- ther microbial speciation (such as via citrate utiliza- fectious Diseases, Department of Medicine, Mayo Clinic tion) would affect patient management. College of Medicine, 200 First St SW, Rochester, MN The single clinical trial using clarithromycin mono- 55905 ([email protected]). therapy noted only 1 case of acquired clarithromycin Author Contributions: Study concept and design: Uslan, resistance (8% of patients), in a noncompliant patient who Kowalski, Virk, and Wilson. Acquisition of data: Uslan, prematurely discontinued therapy.35 There are other case Kowalski , and Wegenack. Analysis and interpretation of reports of clarithromycin resistance developing in data: Uslan, Kowalski, Wegenack, Virk, and Wilson. Draft- patients with M chelonae infection while receiving ing of the manuscript: Uslan and Wilson. Critical revision therapy,36-39 and monotherapy with this agent should be of the manuscript for important intellectual content: Uslan, undertaken with caution. Although there are other case Kowalski, Wegenack, Virk, and Wilson. Statistical analy- reports of effective use of single agents,15,32,40 combina- sis: Uslan and Kowalski. Administrative, technical, and ma- tion therapy seems prudent initially because of con- terial support: Virk and Wilson. Study supervision: Virk cerns about acquired resistance (particularly in dissemi- and Wilson. nated disease, with increased organism burden and Financial Disclosure: None reported. heightened risk of resistance). None of 7 patients in our Previous Presentation: This study was presented in part series who failed therapy developed acquired antimicro- at the American College of Physicians 2006 Annual Ses- bial resistance. Death from cutaneous rapidly growing sion; April 7, 2006; Philadelphia, Pa. mycobacterial infection seems to be rare; most patients have had symptoms for a median of 3 months; and sus- REFERENCES ceptibility testing is usually available promptly. In isolated nondisseminated disease, it may be reasonable to 1. Medical Section of the American Lung Association. Diagnosis and treatment of await results of susceptibility testing rather than to em- disease caused by nontuberculous mycobacteria: this official statement of the pirically start antimicrobials such as aminoglycosides, American Thoracic Society was approved by the Board of Directors, March 1997. which may have serious adverse effects, especially in older Am J Respir Crit Care Med. 1997;156(pt 2):S1-S25. patients or in those with other comorbidities such as re- 2. Wallace RJ Jr, Swenson JM, Silcox VA, Good RC, Tschen JA, Stone MS. Spec- trum of disease due to rapidly growing mycobacteria. Rev Infect Dis. 1983; nal disease. 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