Clinical Characteristics and Treatment Outcomes of Mycobacterium fortuitum Pulmonary Disease

ABSTRACT

We evaluated the clinical characteristics and treatment outcomes of 35 patients diagnosed with Mycobacterium fortuitum-pulmonary disease (M. fortuitum-PD). Prior to treatment, all isolates were sensitive to amikacin and 73% and 90% were sensitive to imipenem and moxifloxacin, respectively. Approximately two-thirds of the patients (24 of 35) remained stable without antibiotic treatment. Of 11 patients requiring antibiotic treatment, the majority (81%, 9 of 11) achieved a microbiological cure with susceptible antibiotics.

IMPORTANCE Mycobacterium fortuitum (M. fortuitum) is a rapidly growing mycobacterium that causes M. fortuitum-pulmonary disease (PD). It is common among individuals with preexisting lung conditions. Limited data exist regarding treatment and prognosis. Our study examined patients with M. fortuitum-PD. Two-thirds of them remained stable without antibiotics. Among those requiring treatment, 81% achieved a microbiological cure with suitable antibiotics. In many cases, M. fortuitum-PD follows a stable course without antibiotics, and when necessary, a favorable treatment response can be achieved with the appropriate antibiotics.

OBSERVATION

The burden of nontuberculous mycobacteria pulmonary disease (NTM-PD) is increasing (1). Mycobacterium fortuitum (M. fortuitum) is a species of rapidly growing mycobacteria commonly found in the environment that can cause M. fortuitum-PD, as well as skin and soft tissue infections (2). M. fortuitum-PD typically occurs in individuals with preexisting pulmonary conditions, such as pulmonary tuberculosis, interstitial lung disease, and/or lung cancer (3). M. fortuitum is not uncommon in respiratory specimens, but the proportion of PD cases requiring antibiotic therapy is relatively low (4, 5). The American Thoracic Society guideline presents diagnostic criteria for NTM-PD, which is primarily suitable for M. avium complex or M. abscessus-PD, and there are limited data to inform the most effective antibiotic treatment and prognosis for M. fortuitum-PD (5). A few case reports of M. fortuitum-PD have appeared, but the efficacy of antibiotic therapy has not been thoroughly established. Reliable data on treatment efficacy are lacking. Thus, we evaluated the clinical characteristics and treatment outcomes of patients with M. fortuitum-PD.

Thirty-five patients meeting the American Thoracic Society diagnostic criteria for M. fortuitum-PD were identified at Samsung Medical Center, South Korea, between January 2006 and December 2021 (5). Among the M. fortuitum-PD patients, there were no coinfections with other NTM strains. Twenty-four did not receive antibiotics (nontreatment group) but the remaining 11 evidenced worsening of respiratory symptoms and radiographic findings, necessitating antibiotic treatment (treatment group). Among the 11 treated patients, the median number of M. fortuitum detections from diagnosis to antibiotic treatment was 4 (interquartile range of 2 to 4 and a range of 2 to 11). We analyzed the clinical features, antibiotic susceptibility test results, types of antibiotics administered, and microbiological responses of the patients. Microbiological response, including acid-fast bacilli (AFB) culture negativity or culture conversion, defined as three consecutive negative tests, were analyzed. Drug susceptibility testing (DST) was conducted by determining the MICs using the broth microdilution method. All data were obtained from an institutional review board-approved observational cohort (ClinicalTrials.gov registration no. NCT00970801) (6). The Pearson χ² test/Fisher exact test was used to compare categorical variables using R version 3.6.1. (R Foundation for Statistical Computing, Vienna, Austria).

Baseline characteristics of the study patients are shown in Table 1. Among the 35 study patients, 46% were aged 65 or older and 49% were male. One-third had a smoking history. The most common underlying condition was a previous tuberculosis, and 57% had nodular bronchiectatic disease (Fig. S1). Twenty-four patients were followed up without antibiotic therapy with a median of 47.0 months (interquartile range of 18.6 to 79.4 months), whereas 11 patients were administered antibiotics. There were no significant differences in characteristics between the two groups.

TABLE 1.

Baseline characteristics of study patients with Mycobacterium fortuitum pulmonary disease^a

Characteristics	Total (n = 35)	Nontreatment group (n = 24)	Treatment group (n = 11)	P value
Age ≥ 65 yrs	16 (46)	14 (58)	2 (18)	0.065
Male	17 (49)	13 (54)	4 (36)	0.539
Body mass index < 18.5 kg/m2	4 (11)	2 (8)	2 (18)	0.781
Current smoker or Ex-smoker	12 (34)	8 (33)	4 (36)	1.000
Underlying conditions
Previous tuberculosis treatment	16 (46)	9 (38)	7 (64)	0.282
Obstructive pulmonary disease	1 (3)	-	1 (9)	0.685
Chronic pulmonary aspergillosis	2 (6)	2 (8)	-	0.840
Symptoms
Cough	23 (66)	13 (54)	10 (91)	0.081
Sputum	26 (74)	16 (67)	10 (91)	0.268
Hemoptysis	6 (17)	3 (13)	3 (27)	0.553
Radiologic form
Fibrocavitary disease	11 (31)	5 (21)	6 (55)	0.084
Nodular bronchiectatic disease	20 (57)	15 (62)	5 (45)	0.084
With cavity	1/20	1/15	-	1.000

^aData are presented as number (percentage) or median (interquartile range).

DST data on all available pretreatment isolates are listed in Table S1. Amikacin demonstrated susceptibility in all strains belonging to the nontreatment and treatment groups. Moxifloxacin exhibited sensitivity in 90% and 89% of the two groups, respectively. With regard to imipenem, 81% and 56% of strains were found to be susceptible in the nontreatment and treatment groups, respectively. Conversely, clarithromycin demonstrated resistance in 62% and 67% of nontreatment and treatment groups, respectively.

The types and durations of antibiotics administered to the 11 patients are detailed in Table 2. All patients received oral macrolide and fluoroquinolone therapy for a median duration of 18.2 months. In three patients, intravenous amikacin and imipenem (cefoxitin) were administered for less than 1 month, and two of them were switched to nonliposomal amikacin inhalation and maintained. The other three patients received oral clofazimine. Among six patients infected with a clarithromycin-resistant strain, all patients commonly received treatment with macrolides and fluoroquinolone. Additionally, among them, two patients initially received amikacin, prepenem, and clofazimine, one patient received amikacin and cefoxitin in addition, one patient received clofazimine in addition, and one patient received rifabutin in addition. The median duration of overall treatment was 18.4 (interquartile range 11.3 to 17.8) months. One patient underwent surgical resection 10 months later due to clarithromycin inducible resistance, drug side effects, the patient's young age, and the large cavity.

TABLE 2.

Treatment modalities in treatment group (n = 11)^a

Antibiotics	Patient	Duration of antibiotics (mo)
PO Macrolide	11 (100)	18.2 (11.7 – 15.6)
PO Fluroquinoloneb	11 (100)	18.2 (13.1 – 17.6)
PO Clofazimine	3 (27)	14.2, 12.4, 2.0
PO Rifabutin	1 (9)	9.9
PO Doxycycline	2 (18)	12.3, 0.3
IV Amikacin	3 (27)	0.9, 0.6, 0.5
After IV, switched to Inhaled Amikacin	2 (18)	2.2, 0.5
IV Imipenem/Cefoxitin	3 (27)	0.9, 0.6, 0.5
Overall treatment duration (mo)		18.4 (11.3–17.8)
Surgical lung resection	1c (9)

^aData are presented as number (percentage) or median (interquartile range). IV, intravenous; PO, per os.

^bOut of the 11 patients, five were administered moxifloxacin, four were given ciprofloxacin, and the remaining two received levofloxacin.

^cAlthough culture negativity was achieved after 1 month of treatment, surgical resection was performed 10 months later due to clarithromycin inducible resistance, drug side effects, the patient's young age, and the large cavity.

Microbiological responses were evaluated based on sputum AFB culture negativity and negative culture conversion after treatment (Table 3). AFB culture negativity rate at 1 month and 3 months after antibiotic treatment was both 64% (7 of 11). Seven out of 11 patients treated with antibiotics achieved a negative culture conversion within 12 months of receiving antibiotics. During the study period, the overall microbiological cure rate was 81% (9 of 11). Of the two patients who did not achieve microbiological cure, one had a clarithromycin-resistant infection and was treated with a combination of macrolide, fluoroquinolone, and clofazimine, while the other had a clarithromycin-sensitive infection and was treated with a combination of macrolide and fluoroquinolone.

TABLE 3.

Microbiological responses after antibiotic treatment^a

Microbiological outcome	Treated group (n = 11)
AFB culture negativity
At 1 mo of treatment	7 (64)
At 3 mo of treatment	7 (64)
At 12 mo of treatment	7 (64)
Culture conversion within 12 mo	7 (64)
Overall microbiological cure rate during study periodb	9 (81)
Time to conversion (mo)	1.0 (0.7–2.2)

^aData are presented as number (percentage) or median (interquartile range). AFB, Acid-fast bacilli.

^bTwo patients did not achieve microbiological cure; one had a clarithromycin-resistant infection and was treated with a combination of macrolide, fluoroquinolone, and clofazimine, while the other had a clarithromycin-sensitive infection and was treated with a combination of macrolide and fluoroquinolone.

In this study, 35 patients diagnosed with M. fortuitum-PD were evaluated, of which the results of 11 (31%) treated patients were reported. Notably, our study reported a microbiological cure rate of 81% for M. fortuitum-PD patients, which is higher than the prior reported cure rates, which were not as high, and fatal cases were more common, particularly in cases with esophageal motility disorder or underlying lung disease (7–10). However, the patient of our study did not have serious underlying conditions, and 64% (7 of 11) of the cases treated were those affected by the so-called Lady Windermere Syndrome. Therefore, our data suggest that the treatment response of M. fortuitum-PD, in patients without severe underlying conditions, is likely to be favorable. Nevertheless, further research data from different regions is required to confirm this.

M. fortuitum is a rapidly growing mycobacteria but, fortunately, is susceptible to more antibiotics than is M. abscessus. In our study, most clinical isolates of M. fortuitum were found to be sensitive to amikacin, imipenem, or moxifloxacin. This indicates that maintenance treatment with drugs such as oral macrolide and fluoroquinolone can be employed following the intensive treatment period with injections in the treatment of M. fortuitum-PD. Notably, favorable responses have been documented with the use of fluoroquinolone antibiotics in previous cases (4, 11, 12). A recent expert consensus on the management of M. fortuitum-PD suggests a regimen composed of two to three drugs, with an injection of amikacin imipenem recommended during the intensive treatment period for several weeks (3). Our study adopted a similar approach; however, further research is warranted to evaluate the efficacy of this regimen.

In our study, we observed some discordance between macrolide DST and treatment outcomes. Despite six patients having clarithromycin-resistant strains, five achieved microbiological cure. This suggests that combining injections (such as amikacin or imipenem) or other oral agents, in addition to macrolides and fluoroquinolones, may enhance treatment effectiveness. Further studies with larger patient cohorts are needed to evaluate treatment outcomes, considering drug resistance and different antibiotic regimens.

In conclusion, approximately two-thirds of patients with M. fortuitum-PD remained stable without antibiotic treatment. Of those requiring antibiotic treatment, the majority (81%) achieved a microbiological cure with susceptible antibiotics.