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In vivo-mimic silkworm infection models with Mycobacterium avium and Mycobacterium intracellulare were newly established to evaluate the therapeutic effects of anti-M. avium complex (MAC) antibiotics. Silkworms raised at 37°C died within 72 hours of an injection of M. avium or M.intracellulare (2.5 × 10 7 colony-forming unit (CFU)/larva·g) into the hemolymph. Clinical anti-mycobacterial (tuberculosis) antibiotics were evaluated under these conditions. Clarithromycin, kanamycin, streptomycin, amikacin, and ciprofloxacin exerted therapeutic effects in a dose-dependent manner, which was consistent with those in the mouse model. Furthermore, three effective actinomycete culture broths were selected in the screening program of our microbial broth library using the silkworm model, and four active metabolites, ohmyungsamycins A and B (1 and 2), chartreusin (3), and griseoviridin (4), were identified. Among these compounds, 1 showed the lowest 50% effective dose (ED 50 ) value (8.5 µg/larva·g), while 3 had the best ED 50 /minimum inhibitory concentration (MIC) ratio (7.4). These results indicate that silkworm models are a useful tool for identifying anti-MAC antibiotics candidates with veritable therapeutic effects.

Background: Mycobacterium avium complex (MAC) and Achromobacter xylosoxidans (AX) are uncommon sources of neurosurgical infections, particularly in immunocompetent hosts. We report the first published case of intracranial AX abscess and polymicrobial AX-MAC abscess, as well as the fourth MAC abscess in a non-immunocompromised patient., Methods: This case report was conducted via retrospective chart review. A literature review was completed in compliance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines., Results: Ten years following mucocele resection, a 60-year-old man presented with sinus congestion and headache. Head imaging revealed a left frontal lesion abutting the cribriform plate and ethmoid roof. The patient had a left frontal craniotomy for abscess drainage. Intraoperative cultures demonstrated polymicrobial growth of AX and MAC, managed with antimicrobial therapy and staged skull base reconstruction. Three cases of MAC abscess and 16 cases of AX ventriculitis or meningitis have been reported in immunocompetent patients. All MAC cerebral abscesses occurred in adults, one of whom succumbed to the infection. Of the 9 AX meningitis cases, 4 occurred in neonates and 2 in pediatric patients. Six of the 7 AX ventriculitis cases occurred after neurosurgical operations at the same hospital from contaminated chlorhexidine basins. Except for the neonates, AX ventriculitis or meningitis patients had undergone neurosurgery or had a history of cranial trauma. There were no reports of polymicrobial AX-MAC intracranial abscess., Conclusions: AX and MAC are rare causes of intracranial infection. Patients with these pathogens identified in the central nervous system require a multidisciplinary approach for successful management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The majority of nontuberculous mycobacterial (NTM) pulmonary infections in people with cystic fibrosis (CF) are caused by Mycobacterium avium complex (MAC) species. Data on MAC species distribution and outcomes of infection in CF are lacking., Methods: This was a single center, retrospective study. MAC isolates had species identification with MLSA of rpoB and the 16S23S ITS region. Clinical data were compared between species., Results: Twenty-three people with CF and 57 MAC isolates were included. Infection with M. avium was the most common (65.2%). M. intracellulare was associated with higher rates of NTM disease, younger age, and steeper decline in lung function prior to infection., Conclusions: We observed worse clinical outcomes in people with M. intracellulare infection relative to other MAC species. Further investigation of clinical outcomes of MAC infection among CF patients is warranted to better define the utility of species-level identification of MAC isolates in CF., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Macrolide antibiotics are cornerstones in the treatment of Mycobacterium massiliense lung disease. Despite the emergence of resistance, limited data on macrolide-resistant M massiliense lung disease are available. This study evaluated the clinical features and treatment outcomes of patients and the molecular characteristics of macrolide-resistant M massiliense isolates. We performed a retrospective review of medical records and genetic analyses of clinical isolates from 15 patients who had macrolide-resistant M massiliense lung disease between September 2005 and February 2015. Nine patients (60%) had the nodular bronchiectatic form of the disease, and six (40%) had the fibrocavitary form. Before the detection of macrolide resistance, three patients (20%) were treated with macrolide monotherapy, four (27%) with therapy for presumed Mycobacterium avium complex infections, and eight (53%) with combination antibiotic therapy for M massiliense lung disease. The median treatment duration after the detection of resistance was 18.7 months (interquartile range, 11.2 to 39.8 months). Treatment outcomes were poor, with a favorable outcome being achieved for only one patient (7%), who underwent surgery in addition to antibiotic therapy. The 1-, 3-, and 5-year mortality rates were 7, 13, and 33%, respectively. Of the 15 clinical isolates, 14 (93%) had point mutations at position 2058 (n = 9) or 2059 (n = 5) of the 23S rRNA gene, resulting in macrolide resistance. Our study indicates that treatment outcomes are poor and mortality rates are high after the development of macrolide resistance in patients with M massiliense lung disease. Thus, preventing the development of macrolide resistance should be a key consideration during treatment., (Copyright © 2017 American Society for Microbiology.)

Purpose of Review: Although the incidence of tuberculosis has reduced in developed countries, there is a growing interest in nontuberculous mycobacteria (NTM) as a cause of lung disease. However, NTM are a heterogeneous group and most of the data come from only three species: Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus. Still, information about these three species is confusing because it is based mainly on retrospective studies and series of clinical cases performed in developed countries. In recent years, new information has appeared about other species and the pathogenesis of NTM., Recent Findings: Epidemiological studies show that NTM infection is a worldwide phenomenon with an increasing presence in developing countries perhaps because of the implementation of tap water. Women with characteristic phenotype are at higher risk of acquiring NTM infection along with patients with defects on cystic fibrosis transmembrane conductance regulators. New studies on Mycobacterium fortuitum, Mycobacterium xenopi, Mycobacterium szulgai and Mycobacterium simiae indicate that the American Thoracic Society criteria for diagnosing NTM disease may not be useful for all species of NTM., Summary: New multicentric and prospective studies are needed to clarify the pathogenesis and treatment of NTM. These organisms form a numerous and heterogeneous group and each species should be studied separately.

Objective: We present a case series and review of the literature of the management options in non-HIV-infected patients with Mycobacterium avium complex pulmonary disease (MAC-PD) with a focus on treatment failure and drug resistant disease., Case Series: Five case histories are presented, depicting various clinical scenarios necessitating different approaches to therapy and highlighting the limitations and complications of these options., Discussion: Mycobacterium avium complex (MAC) is well recognized as a significant cause of pulmonary disease in non-HIV infected patients and in those with intact immunity. Isolation of non-tuberculous mycobacteria (NTM) in culture is essential for the diagnosis of NTM lung disease. The typical presentation of MAC lung disease is apical fibrocavitary lung disease in men in their late 40s and early 50s who have a history of cigarette smoking and, frequently, excessive alcohol use. Other presentations of NTM lung disease include nodular bronchiectasis, solitary or multiple pulmonary nodules, and hypersensitivity pneumonitis. When indicated, the standard recommended treatment for most patients is a three-times-weekly regimen of clarithromycin or azithromycin, rifampin, and ethambutol with or without amikacin. Daily therapy is recommended for fibrocavitary disease. Based on published studies, macrolides are the only agents used for treatment of MAC disease for which there is a correlation between in vitro susceptibility and in vivo (clinical) response. Data regarding treatment of macrolide-resistant MAC (MRMAC) and multi-drug resistant MAC (MDRMAC) is sparse. Several drugs have been evaluated in drug-resistant MAC and have potential as effective therapy. Use of multiple drugs to which the isolate is susceptible is preferred to avoid development of future resistance. Surgery in mycobacterial disease is technically difficult, but selected patients with focal disease do benefit from resection of the involved lung., Conclusions: MAC has protean pulmonary manifestations, especially in those with no recognizable impairments in their immune system. Drug treatment, however, remains difficult with high failure rates and poor long-term sputum conversion. This case series is based on our clinical experience highlighting treatment options and the often unrecognized morbidity and mortality of severe, progressive MAC-PD. It underscores the need for increased awareness of MAC-PD and MDRMAC and the difficulties encountered in their management.

Three children, a girl aged 2.5 years and two boys aged 2 and 3 years respectively, presented with unilateral cervical lymphadenitis. The first patient had acute bacterial lymphadenitis due to group A Streptococcus, characterised by a painful cervical swelling of acute onset. The second patient had painless cervical lymphadenitis caused by Mycobacterium avium-intracellulare, which drained spontaneously. The third patient developed a non-tender, cervical swelling within a day. He too was systemically ill with fever and a headache. The lymphadenitis was caused by Bartonella henselae. After drainage, dissection and/or antibiotic therapy, all three recovered. A cervical mass in a young child is most frequently caused by an infectious lymphadenopathy. It rarely represents a malignant or other systemic disease. In many cases the diagnosis of infectious lymphadenitis can be made on the basis of the case history and clinical characteristics. However, when malignancy cannot be excluded tissue examination is always indicated.

Resistance to clarithromycin in breakthrough Mycobacterium avium complex (MAC) isolates typically occurs 3 to 4 months after the initiation of monotherapy in bacteremic AIDS patients. It has been suggested that continuation of clarithromycin therapy still results in clinical and microbiological improvement. To study this paradox, C57BL/6 beige mice were infected with a clarithromycin-resistant (MIC, > or =128 microg/ml) strain of MAC 101 (CLA-R MAC 101) and treated with 200 mg of clarithromycin per kg of body weight/day alone or in combination with ethambutol (100 mg/kg/day) for 2 weeks. Mice infected with a clarithromycin-susceptible strain of MAC 101 had bacterial loads reduced by 90% in the liver and 91% in the spleen (P<0.05, compared with the control). Clarithromycin treatment of CLA-R MAC 101 resulted in a 65% reduction of bacterial loads in the liver (P = 0.009) and a 71% reduction in the spleen (P = 0.009), compared with the results for the untreated control. CLA-R MAC 101 and MAC 101 (isogenic strains) had comparable growth rates in murine tissue, ruling out a loss of virulence of CLA-R MAC 101. Strains of MAC currently defined as macrolide resistant may still respond to treatment with an agent such as clarithromycin within infected tissues.

The incidence of identification of nontuberculous mycobacteria has increased since the advent of the acquired immunodeficiency syndrome epidemic. Although Mycobacterium avium complex appears to be responsible for most episodes of nontuberculous disease, several other previously rare species are increasingly being detected, including Mycobacterium kansasii, Mycobacterium fortuitum/chelonei complex, and Mycobacterium genavense. This review briefly summarizes the epidemiology and clinical features of these infections, as well as therapeutic and preventive strategies in immunosuppressed patients with nontuberculous mycobacterial infections. Of clinical relevance, nontuberculous mycobacterial infections are difficult to treat and do not respond to traditional antituberculous agents. The search for more effective treatment regimens is ongoing in an attempt to enhance survival and reduce morbidity among immunocompromised patients. Novel antimicrobial combinations that include clarithromycin or azithromycin have been shown to be effective in treating several nontuberculous mycobacterial infections.