Mycobacterium septicum: a 6-Year Clinical Experience from a Tertiary Hospital and Reference Laboratory

Mycobacterium septicum is a rarely identified nontuberculous mycobacterium capable of causing infections in both healthy and immunocompromised individuals. Only a few cases of M. septicum infections have been reported, which makes recognizing corresponding clinical disease more challenging for clinicians. Antimicrobial susceptibility profiles for this organism are not well described, and corresponding optimal therapeutic regimens have not been established. We report a tertiary care center’s experience with M. septicum from 2014 to 2020.

ABSTRACT

Mycobacterium septicum is a rarely identified nontuberculous mycobacterium capable of causing infections in both healthy and immunocompromised individuals. Only a few cases of M. septicum infections have been reported, which makes recognizing corresponding clinical disease more challenging for clinicians. Antimicrobial susceptibility profiles for this organism are not well described, and corresponding optimal therapeutic regimens have not been established. We report a tertiary care center’s experience with M. septicum from 2014 to 2020. Twelve adult patients with positive cultures for M. septicum were identified. Most cases were identified from sputum samples of individuals with underlying lung disease. Most cases involving M. septicum isolation in culture were not felt to be clinically significant. Two cases were considered possible infections, while only one case was considered a definite infection that required antimicrobial treatment. All M. septicum isolates were susceptible in vitro to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole. Isolates were universally resistant to clarithromycin and doxycycline. The isolation of M. septicum in culture is uncommon and requires clinical correlation to determine its clinical relevance and need for treatment. Susceptibility testing should be performed to guide therapy.

INTRODUCTION

Nontuberculous mycobacteria (NTM) are ubiquitous organisms found in the natural environment, including soil and water. Over 200 species of NTM have been identified, and with advances in culture techniques and increasing utilization of molecular sequencing, the list continues to grow (1–4). While now considered outdated due to molecular detection methods, NTM have traditionally been categorized using the Runyon system of classification, which divides organisms based on growth rates, colony morphology, and pigmentation (5). Mycobacterium septicum is classified as a Runyon type IV rapidly growing mycobacteria (RGM) that typically produces mature growth on culture media within 7 days. It is phenotypically a member of the M. fortuitum group (MFG), which is composed of 10 closely related species of NTM that can cause pulmonary and extrapulmonary infections and include the following: M. fortuitum, M. boenickei, M. brisbanense, M. porcinum, M. houstonense, M. neworleansense, M. peregrinum, M. senegalense, M. setense, and M. septicum (4, 6–8). Species belonging to this group are usually more susceptible to a variety of antimicrobials than members of the M. abscessus-M. chelonae complex. Most MFG species demonstrate in vitro macrolide resistance conferred by the erythromycin-inducible methylase (erm) gene (6); however, M. peregrinum, M. conceptionense, and M. senegalense do not harbor the erm gene and are typically macrolide susceptible unless they are mutationally resistant (9).

M. septicum was first identified as a causative agent of central line-related bloodstream infection in a child with metastatic hepatoblastoma and corresponding sepsis (10). Since identification, only seven cases have been reported, including two lung infections, two skin and soft tissue infections, two catheter-related bloodstream infections, and a case of peritoneal dialysis (PD) catheter-related peritonitis (10–16). Due to limited published information on M. septicum as a distinct species, the more common clinical presentations and optimal management approaches are not well-defined. We describe clinical features, management, and outcomes of 12 patients identified with M. septicum isolated from cultures in our institution and present antimicrobial susceptibility patterns of the isolates.

MATERIALS AND METHODS

The study was approved by the Mayo Clinic Institutional Review Board. We conducted a retrospective case review of all patients seen at the Mayo Clinic in Rochester, Minnesota, from July 2014 to March 2020 from whom M. septicum was isolated in culture by our clinical microbiology laboratory. The patients’ medical records, including clinical assessments, pathology results, surgical findings, laboratory and microbiologic data, imaging studies, and medications, were reviewed.

Specimens were cultured in BD Bactec MGIT 960 broth in mycobacterial growth indicator tubes (Becton, Dickinson and Company, Franklin Lakes, NJ) and on Middlebrook 7H11/7H11S agar biplates incubated at 35 to 37°C for up to 6 weeks. Positive MGIT broth was subcultured to a Middlebrook 7H11 agar plate, and isolated colony growth was identified using matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (Bruker Scientific, Billerica, MA) as previously described (17). Antimicrobial susceptibility testing was performed using Clinical and Laboratory Standards Institute (CLSI) guidelines (8) using the Sensititre Rapmyco antimicrobial susceptibility plate (Trek/Thermo Fisher Scientific, Oakwood Village, OH) for rapidly growing mycobacteria. Interpretation of the MIC as susceptible, intermediate, or resistant for each isolate was done using current CLSI interpretive criteria (27).

RESULTS

We identified 12 patients with positive cultures for M. septicum over the study period. Seven patients were male, and five were female (Table 1). The average age was 67 years, with an age range of 48 to 80 years. Seven of the M. septicum cultures were from sputum samples, whereas five were from extrapulmonary sources.

TABLE 1.

Patient demographics and specimen sources of M. septicum isolates

Characteristic	Value
Patient demographics
Mean age (yrs [range])	66.9 (48–80)
Male (no. of patients [%])	7 (58.3)
Female (no. of patients [%])	5 (41.7)
Specimen source (no. of patients [%])
Sputum	7 (58.3)
Tissue
Lymph node	1 (8.3)
Leg	1 (8.3)
Shoulder	1 (8.3)
Calf	1 (8.3)
Peritoneal fluid	1 (8.3)

Patient cases.

Case 1 is a 54-year-old man with systemic sclerosis and end-stage kidney disease on PD who developed progressive abdominal pain and distention. Physical examination was consistent with ascites. Paracentesis was performed and demonstrated 154 total nucleated cells per microliter with neutrophilic predominance. Peritoneal fluid mycobacterial culture grew M. septicum after 3 days. His PD catheter was removed, and he was initially treated with moxifloxacin and doxycycline. Once susceptibility results became available, doxycycline was replaced with trimethoprim-sulfamethoxazole while moxifloxacin was continued (Table 2). He subsequently developed pancytopenia, and trimethoprim-sulfamethoxazole was changed to intravenous amikacin. Upon developing ototoxicity, amikacin was changed to oral linezolid, and moxifloxacin was continued. Peritoneal fluid cultures showed no mycobacterial growth after 2 weeks of treatment, and he successfully completed 4 additional months of treatment after culture conversion (total of 18 weeks of therapy).

TABLE 2.

Patient characteristics, therapy provided, and outcomes

Case	Age/sex	Comorbidity(s)	Specimen source	Immunosuppressiona	Macrolide exposure	Contaminant, colonizer, or pathogen	Therapy	Outcome
1	54/M	Systemic sclerosis, ESKDb	Peritoneal fluid	No	No	Pathogen	Peritoneal dialysis catheter removal; linezolid plus moxifloxacin (4 mo)	Death
2	77/F	Bronchiectasis, asthma	Sputum	No	Yes	Possible pathogen	Moxifloxacin plus rifampin plus clarithromycin plus nebulized amikacin (15 mo); moxifloxacin plus rifampin plus clofazimine plus nebulized amikacin (3 mo); moxifloxacin plus rifampin plus clofazimine (4 yrs)	Survived, alive
3	73/M	Bronchiectasis	Sputum	No	Yes	Colonizer	None	Survived, alive
4	76/F	Squamous cell cancer of the tongue	Lymph node tissue	No	No	Contaminant	Aspiration; none	Survived, alive
5	75/M	Rheumatoid arthritis	Sputum	Yes	Yes	Colonizer	None	Survived, alive
6	48/M	Cystic fibrosis	Sputum	No	Yes	Colonizer	None	Survived, alive
7	75/F	Bronchiectasis, Crohn's disease	Sputum	No	No	Possible pathogen	None (refused treatment)	Survived, alive
8	67/F	Bronchiectasis	Sputum	No	No	Colonizer	None	Survived, alive
9	54/M	None	Leg tissue	No	No	Contaminant	Transtibial amputation; none	Survived, alive
10	67/F	Bicuspid aortic valve s/p AVRb	Shoulder tissue	No	No	Contaminant	None	Survived, alive
11	57/M	None	Calf tissue	No	No	Contaminant	Irrigation and debridement; none	Survived, alive
12	80/M	Rheumatoid arthritis, bronchiectasis	Sputum	No	No	Colonizer	None	Survived, alive

^aImmunosuppression includes steroids and/or use of other immunosuppressive agents.

^bESKD, end-stage kidney disease; AVR, aortic valve replacement.

Case 2 is a 77-year-old woman with asthma, bronchiectasis, and Mycobacterium avium complex (MAC) pulmonary disease. She was diagnosed with acid-fast bacilli (AFB) smear-positive pulmonary MAC disease after presenting with chronic productive cough and multiple positive sputum cultures for MAC. Chest computed tomography (CT) showed bilateral bronchiectasis and fibronodular infiltrates involving multiple lung lobes. She was treated with clarithromycin, ethambutol, and rifampin for 1 year, but she developed optic neuropathy, prompting a switch from ethambutol to moxifloxacin. She continued to receive moxifloxacin, rifampin, and clarithromycin for another 2 years due to persistently positive AFB smears and mycobacterial cultures. Three years into treatment, surveillance sputum cultures obtained grew MAC and one colony of M. septicum after 23 days. Susceptibility testing showed macrolide resistance for both MAC and M. septicum, prompting an escalation in her regimen to treat both. With the susceptibility profile outlined in Table 3, she was placed on a four-drug regimen consisting of moxifloxacin, rifampin, clarithromycin, and nebulized amikacin for 15 months. Following insurance approval of clofazimine, she was placed on moxifloxacin, rifampin, clofazimine, and nebulized amikacin. She became intolerant of nebulized amikacin, which was discontinued after 3 months. She reported symptomatic improvement but continued on therapy as her sputum cultures remained positive for MAC. M. septicum was never isolated again, and its pathogenicity and contribution to disease, in this case, remain unclear.

TABLE 3.

Antimicrobial susceptibility profiles and MICs of Mycobacterium septicum isolates

Isolate	MIC (μg/ml) (susceptibility)a of:
	Amikacin	Cefoxitin	Ciprofloxacin	Clarithromycin	Doxycycline	Imipenem	Linezolid	Moxifloxacin	Tigecycline	TMP-SMX
1	8 (S)	32 (I)	≤0.12 (S)	>16 (R)	16 (R)	4 (S)	8 (S)	≤0.25 (S)	0.06 (NI)	≤0.25/4.75 (S)
2	≤1 (S)	32 (I)	≤0.12 (S)	16 (R)	16 (R)	≤2 (S)	8 (S)	≤0.25 (S)	0.03 (NI)	≤0.25/4.75 (S)
3	≤1 (S)	32 (I)	≤0.12 (S)	8 (R)	>16 (R)	4 (S)	2 (S)	≤0.25 (S)	0.06 (NI)	≤0.25/4.75 (S)
4	2 (S)	64 (I)	≤0.12 (S)	8 (R)	16 (R)	4 (S)	4 (S)	≤0.25 (S)	0.06 (NI)	≤0.25/4.75 (S)
5	4 (S)	32 (I)	≤0.12 (S)	16 (R)	8 (R)	≤2 (S)	2 (S)	≤0.25 (S)	0.06 (NI)	≤0.25/4.75 (S)
6	≤1 (S)	32 (I)	≤0.12 (S)	>16 (R)	16 (R)	≤2 (S)	8 (S)	≤0.25 (S)	0.06 (NI)	≤0.25/4.75 (S)
7	≤1 (S)	128 (R)	≤0.12 (S)	>16 (R)	>16 (R)	≤2 (S)	2 (S)	≤0.25 (S)	0.03 (NI)	0.5/9.5 (S)
8	≤1 (S)	32 (I)	0.5 (S)	>16 (R)	>16 (R)	≤2 (S)	≤1 (S)	≤0.25 (S)	0.06 (NI)	≤0.25/4.75 (S)
9	2 (S)	64 (I)	≤0.12 (S)	8 (R)	>16 (R)	≤2 (S)	4 (S)	≤0.25 (S)	0.25 (NI)	0.5/9.5 (S)
10	4 (S)	32 (I)	0.25 (S)	8 (R)	8 (R)	4 (S)	4 (S)	≤0.25 (S)	0.06 (NI)	≤0.25/4.75 (S)
11	4 (S)	32 (I)	0.25 (S)	>16 (R)	16 (R)	4 (S)	8 (S)	≤0.25 (S)	0.12 (NI)	2/38 (S)
12	≤1 (S)	32 (I)	≤0.12 (S)	16 (R)	8 (R)	≤2 (S)	2 (S)	≤0.25 (S)	0.12 (NI)	1/19 (S)

^aS, susceptible; I, intermediate; R, resistant; NI, no interpretation; TMP-SMX, trimethoprim-sulfamethoxazole.

Case 3 is a 73-year-old man with bronchiectasis who presented with 4 weeks of productive cough and night sweats. Chest CT showed bronchial dilation and nodular and consolidative infiltrates with tree-in-bud changes predominantly involving the bilateral lower lobes. Bronchoscopy was performed, and the bronchoalveolar lavage (BAL) fluid sample was negative for AFB staining but grew MAC in culture. He was diagnosed with MAC pulmonary disease and started on azithromycin, rifampin, and ethambutol. The patient had symptomatic improvement and sputum culture conversion after 3 months. While on therapy, he developed a worsening cough, prompting reculturing of sputum. Two sputum samples were obtained, and both stained negative for AFB. One of two mycobacterial cultures grew M. septicum after 41 days, which was not considered clinically significant. He was treated with daily rifampin, azithromycin, and ethambutol for 6 months with near resolution of symptoms and then placed on the same regimen thrice weekly for another 9 months. He completed 12 months of therapy following culture conversion with complete resolution of symptoms along with radiographic improvement.

Case 4 is a 76-year-old woman with a history of squamous cell carcinoma of the tongue status postresection and adjuvant radiation therapy with multiple recurrences requiring several surgeries, including mandible resection and reconstruction. Due to tissue breakdown, she had further debridement and reconstructive surgery. Postoperatively, she developed a tender mass on the right side of her neck. CT of the neck showed a 2.1-cm peripherally enhancing, centrally low-attenuation lesion within the superficial soft tissues of the neck, concerning for an abscess or a necrotic lymph node. An ultrasound-guided biopsy specimen with fluid aspiration showed skeletal muscle and nonnecrotizing granulomatous inflammation. The tissue AFB stain was negative, but bacterial culture grew M. septicum after 3 days. She was given a 7-day course of amoxicillin-clavulanic acid, and on follow-up, she was asymptomatic with noted complete resolution of the mass. M. septicum was not felt to be a contributing pathogen to disease.

Case 5 is a 75-year-old man with a 60-pack-year smoking history and rheumatoid arthritis who was on methotrexate, hydroxychloroquine, and certolizumab. He had a chronic nonproductive cough, and chest CT revealed bilateral lower lobe consolidation and right lung nodular opacities. Sputum samples stained negative for AFB; however, one of three samples grew Nocardia nova on mycobacterial culture. Trimethoprim-sulfamethoxazole monotherapy was planned, but due to concerns for multiple drug interactions, he was instead treated with azithromycin for 7 months. A follow-up sputum sample obtained after 1 month stained negative for AFB but grew M. septicum on mycobacterial culture after 8 days. M. septicum-directed therapy was not initiated, as it was not felt to be contributing to disease. He had complete resolution of symptoms, and follow-up chest CT showed near resolution of the right lung opacities.

Case 6 is a 48-year-old man with cystic fibrosis lung disease with pancreatic insufficiency and secondary biliary cirrhosis who demonstrated a progressive decline in his vital capacity and volume reduction in forced expiratory volume in 1 s (FEV1) over the preceding few years. His airways were known to be colonized with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Aspergillus fumigatus, and he was maintained on azithromycin thrice weekly for immunomodulatory benefit. A sputum sample stained negative for AFB. Bacterial culture grew MRSA, and mycobacterial culture grew M. septicum after 4 days. Antimicrobial therapy for M. septicum was not initiated, as it was considered a colonizer, and he continued to do well.

Case 7 is a 75-year-old woman with bronchiectasis, Crohn's disease, and short bowel syndrome secondary to multiple small-bowel resections who had progressively worsening productive cough over the last 2 years. A review of records revealed two prior sputum cultures that grew MAC, which were assessed to be airway colonization in the setting of bronchiectasis. Chest CT revealed a left lower lobe consolidation and a left upper lobe semisolid nodule. A sputum sample stained negative on AFB. Aspergillus ustus grew on fungal culture. Mycobacterial culture grew MAC and M. septicum after 25 days. Treatment was offered, but she refused due to a personal history of difficulty tolerating antimicrobials. Close follow-up was recommended. During her subsequent visit, she reported symptomatic improvement, and a chest CT showed a stable left upper lobe nodule and interval improvement in the left lower lobe consolidation.

Case 8 is a 67-year-old woman with chronic rhinosinusitis and bronchiectasis who developed a progressively worsening productive cough associated with exertional dyspnea. Chest CT showed bilateral diffuse bronchiectasis with associated nodular infiltrates and patchy areas of consolidation most prominent in the left lower lobe. A sputum sample stained negative for AFB but grew M. septicum on mycobacterial culture after 29 days. A pulmonary hygiene regimen with twice-daily albuterol nebulization followed by hypertonic saline was commenced without introducing any antimicrobial therapy. She reported complete resolution of her respiratory symptoms on a 2-month follow-up. Chest CT showed improvement in the bronchial wall thickening and micronodular infiltrates. A follow-up sputum sample stained negative for AFB and had no growth on mycobacterial culture.

Case 9 is a 54-year-old immunocompetent man involved in a motor vehicle accident that led to multiple fractures, including right superior and inferior pubic rami fractures, an open midshaft left tibia fracture, and distal left femur fracture with associated soft tissue loss. He underwent left lower extremity wound exploration and knee-spanning external fixator placement. Wound and tissue cultures grew Staphylococcus epidermidis, Klebsiella oxytoca, Enterococcus faecalis, and Bacillus sp. on bacterial culture, M. septicum on mycobacterial culture after 22 days, and Rhizomucor sp., Alternaria sp., Fusarium sp., and Aspergillus fumigatus on fungal culture. The patient had multiple other surgical procedures, including several irrigations, debridements, and flap and skin graft placements, but he ultimately underwent a left transtibial amputation. He was treated with ertapenem, daptomycin, liposomal amphotericin B, and isavuconazole for 6 weeks with complete recovery. Directed therapy against M. septicum was not initiated, as it was labeled a contaminant.

Case 10 is a 67-year-old woman with a mechanical aortic valve who presented with increasing left shoulder pain. An X-ray showed advanced degenerative changes, while CT scan revealed destructive arthritis of the left glenohumeral joint. Surgical management was pursued, and she underwent an anatomic left total shoulder arthroplasty. One of three intraoperative cultures grew M. septicum on mycobacterial culture after 28 days. It was suspected to be a contaminant, and she continued to do well without antimicrobial treatment.

Case 11 is a 57-year-old immunocompetent man involved in a motor vehicle accident that resulted in multiple injuries, including a right open femur fracture, left tibia plateau fracture, bilateral wrist fractures, and avulsion of the skin and subcutaneous tissues of his right hand. He underwent several open reduction and internal fixation procedures and numerous debridements. Multiple tissue cultures obtained from his right leg grew Cellulosimicrobium sp., Stenotrophomonas maltophilia, Paenibacillus sp., Nocardia abscessus complex, Candida albicans, Fusarium sp., Mucor sp., and M. septicum, which grew on mycobacterial culture after 6 days. He was initially treated with posaconazole, liposomal amphotericin B, levofloxacin, and trimethoprim-sulfamethoxazole. Given the low likelihood of a functional limb, he underwent a right above-the-knee amputation. He underwent multiple subsequent irrigations and debridements and was treated with trimethoprim-sulfamethoxazole and posaconazole for a total of 6 weeks. M. septicum was considered a contaminant within this polymicrobial infection; however, the isolate was found to be susceptible to both trimethoprim-sulfamethoxazole and fluoroquinolones, which he received.

Case 12 is an 80-year-old man with rheumatoid arthritis and chronic bronchiectasis who presented with worsening productive cough and exertional dyspnea. Pulmonary function testing revealed a moderate reduction in diffusion lung capacity for carbon monoxide (DLCO), a normal FEV1, and reduced FEV1/forced vital capacity (FVC) ratio. Chest CT showed bibasilar bronchiectasis. A sputum sample stained negative for AFB but grew MAC and M. septicum on culture after 20 days. A pulmonary hygiene program consisting of twice-daily albuterol nebulization followed by hypertonic saline and use of an oscillating positive expiratory device was initiated. Antimycobacterial drug therapy was not initiated, as he had symptomatic improvement on follow-up.

Patient and culture characteristics.

Among the 12 patients identified with M. septicum on culture, only one patient was on an immunosuppressive medication. Four patients had prolonged macrolide exposure prior to the isolation of M. septicum. M. septicum was isolated from a single specimen sample in all of the patients, except for the patient with peritonitis (case 1) who had two peritoneal fluid cultures that grew the organism.

Among the seven patients with M. septicum isolated from sputum culture (cases 2, 3, 5, 6, 7, 8, and 12), six had underlying lung disease. Additionally, MAC was isolated along with M. septicum in three of the seven pulmonary samples. Most isolates obtained from sputum samples were considered airway colonizers or only reflective of minimal disease, not requiring targeted antimicrobial therapy. Of these pulmonary cases, only two cases (cases 2 and 7) were considered clinically significant and possibly pathogenic.

Among the five extrapulmonary cases (cases 1, 4, 9, 10, and 11), two (cases 9 and 11) involved polymicrobial trauma-related infections, and M. septicum was isolated with multiple other organisms. One isolate (case 4) was obtained from a lymph node aspirate. Another isolate (case 10) was from shoulder tissue. Except for case 1, directed antimycobacterial therapy was not initiated in the other four extrapulmonary cases, as M. septicum was considered a contaminant. PD catheter-related peritonitis was seen in the remaining extrapulmonary isolate (case 1), and therapy was directed against M. septicum, along with catheter removal.

A total of two patients received antimycobacterial treatment, one of whom survived with good outcomes, including symptomatic and radiographic improvement up until follow-up. All the patients with positive M. septicum cultures labeled as either a contaminant or a colonizer did not receive antimycobacterial therapy and are alive at the time of writing. All the M. septicum isolates were susceptible in vitro to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole (Table 3). The isolates were found to be resistant to clarithromycin and doxycycline. Most isolates had intermediate susceptibility to cefoxitin.

DISCUSSION

M. septicum is an unusual cause of NTM infection. Its ubiquitous nature allows it to potentially cause infection in any organ. Catheter-related infections, including bloodstream infections and PD catheter-related peritonitis caused by RGM in individuals with long-term catheters, have been described (18, 19). Interestingly, only 1 of the 12 patients in our series was felt to have definitive M. septicum disease and received directed treatment. Two patients were considered to have possible infection, and one received antibiotic treatment with activity against both MAC and M. septicum. In the other nine patients, M. septicum either represented an airway commensal, sample contaminant, or minimally pathogenic not necessitating therapy. The isolation of M. septicum from sterile sources, including cerebrospinal fluid (CSF), blood, peritoneal fluid, pleural fluid, and joint fluid, would likely warrant treatment; however, its isolation from respiratory samples requires additional assessment of whether this organism reflects an airway commensal or a pathogen requiring treatment. Indeed, the vast majority of patients in our series with M. septicum isolated from respiratory samples did not require specific antimicrobial treatment against M. septicum and generally did well. This finding is consistent with other reports of MFG species isolated from respiratory samples that did not require therapy, as airway colonization and/or relative minor disease contribution not requiring treatment are commonly encountered (20, 21). When M. septicum is isolated from a respiratory culture, clinical correlation of active patient symptoms with radiologic findings, as well as the assessment for other potential pathogens, is thus important in deciding whether antimicrobial treatment is needed.

Individuals with underlying structural lung disease are likely to be at increased risk of developing pulmonary NTM infection, including those caused by M. septicum and other MFG; however, as our case series finds, airway colonization with M. septicum is relatively common and does not always warrant treatment. The majority of cases with M. septicum isolated from a respiratory source were symptomatic patients, and all but one had underlying lung disease. The clinical significance of isolating M. septicum from one sputum sample is of questionable value and often represents colonization. Like other NTM, at least two positive sputum cultures from separate samples or at least one positive NTM culture from a bronchial wash or lavage or a lung biopsy specimen showing granulomatous inflammation, along with one or more sputum or bronchial washings that are culture positive for NTM, would be needed to meet microbiologic criteria for the diagnosis of NTM lung disease (22, 23).

M. septicum was isolated with another organism in four pulmonary cases, including three with MAC and one with MSSA, reflective of the patient’s underlying structural lung disease, including chronic obstructive pulmonary disease (COPD) and bronchiectasis. In this setting, initiation of an optimized pulmonary hygiene program (e.g., use of a bronchodilator, hypertonic saline, oscillatory device, etc.) to evacuate retained endobronchial mucous and avoid plugging is an important management strategy. Nevertheless, MFG, including M. septicum, can produce pulmonary disease in select patients, especially in those with gastroesophageal disease, including achalasia and gastroesophageal reflux disease, and in those with lipoid pneumonia (20, 24–26). Four patients were identified to have had prolonged exposure to either clarithromycin or azithromycin prior to the isolation of M. septicum, which may have enabled selection of this organism with known inducible resistance to clarithromycin. M. septicum, like the vast majority of MFG members, demonstrates macrolide resistance, either by inducible erm gene expression or other mechanisms (6).

Generalized treatment recommendations for M. septicum are limited by the lack of published cases and prospective controlled trials; hence, optimal antibiotic regimens and treatment duration have not been firmly established. For MFG, combination therapy with at least two active agents in vitro is recommended (22). All M. septicum isolates tested at our center were susceptible to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole (Table 4). Consistent with prior studies on macrolide susceptibility of MFG, a high rate of macrolide resistance was demonstrated in our case series. All the isolates were found to be resistant to both clarithromycin and doxycycline. More clinical isolates and their corresponding susceptibility profiles are still needed to develop a data repository to guide clinicians in selecting appropriate antibiotics.

TABLE 4.

Results of antimicrobial susceptibility testing of Mycobacterium septicum isolates

Species (no. of cases)	% susceptibility of:
	Amikacin	Cefoxitin	Ciprofloxacin	Clarithromycin	Doxycycline	Imipenem	Linezolid	Moxifloxacin	Tigecycline	TMP-SMXa
M. septicum (n = 12)	100	0	100	0	0	100	100	100	NI	100

^aTMP-SMX, trimethoprim-sulfamethoxazole; NI, no interpretation.

In conclusion, most cases of M. septicum isolated in culture within our series were not considered clinically significant and did not require antimicrobial therapy. When M. septicum is isolated in culture, clinical correlation is needed to determine if treatment is indicated. All M. septicum isolates were susceptible in vitro to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole. Isolates were universally resistant to clarithromycin and doxycycline. As molecular diagnostic platforms continue to advance, along with increasing awareness of the different species of NTM, more cases of M. septicum will likely be encountered in clinical practice, which would enable a better understanding of this organism and its associated infectious syndromes.