Omadacycline therapy for Mycobacterium abscessus species infections.

BACKGROUND: Antimicrobial resistance and therapy-related adverse effects make Mycobacterium abscessus treatment challenging. Omadacycline is a novel, bioavailable aminomethylcycline with favourable in vitro activity against M. abscessus. AIMS: To describe a case report and review the published literature describing outcomes for M. abscessus infections treated with omadacycline. METHODS: Systematic literature review. RESULTS: We identified three articles that, in addition to our case report, describe 18 patients. Pulmonary infections were most frequent. Minimum inhibitory concentrations were reported for two isolates (0.25 and 0.5 mg/L). Despite half the patients starting omadacycline because of failure of prior therapy, 15 (83%) had a favourable outcome, defined as 'cure', 'improvement' or 'clinical success' as determined by the primary study authors. One patient (6%) discontinued omadacycline because of gastrointestinal intolerance. CONCLUSIONS: Although the limited observational data and in vitro susceptibility results are encouraging, randomised control trials are required to determine the role of omadacycline as part of combination therapy for this most difficult-to-treat pathogen.

Mycobacterium chimaera colonisation of heater-cooler units (HCU) in Western Australia, 2015: investigation of possible iatrogenic infection using whole genome sequencing.

Following the reported link between heater-cooler unit (HCU) colonisation with Mycobacterium chimaera and endocarditis, mycobacterial sampling of all HCUs in use in Western Australia was initiated from August 2015, revealing M. chimaera colonisation in 10 of 15 HCUs. After M. chimaera was isolated from a pleural biopsy from a cardiothoracic patient who may have been exposed to a colonised HCU, a whole genome sequencing investigation was performed involving 65 specimens from 15 HCUs across five hospitals to assess if this infection was related to the HCU. Genetic relatedness was found between the 10 HCU M. chimaera isolates from four hospitals. However the M. chimaera isolate from the cardiothoracic patient was not genetically related to the HCU M. chimaera isolates from that hospital, nor to the other HCU isolates, indicating that the HCUs were not the source of the infection in this patient.

Tuberculosis in Australia: bacteriologically-confirmed cases and drug resistance, 2011. A report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collects and analyses laboratory data on new cases of disease caused by the Mycobacterium tuberculosis complex. In 2011, a total of 1,057 cases were identified bacteriologically; an annual reporting rate of 4.6 cases per 100,000 population. Eighteen children aged less than 15 years plus an additional 11 children from the Torres Strait Protected Zone had bacteriologically-confirmed tuberculosis. Results of in vitro drug susceptibility testing were available for 1,056 isolates for isoniazid, rifampicin, ethambutol, and pyrazinamide. A total of 107 (10.0%) isolates of M. tuberculosis were resistant to at least one of these anti-tuberculosis agents. Resistance to at least isoniazid and rifampicin (defined as multi-drug resistance, MDR) was detected in 25 (2.4%) isolates; 18 were from the respiratory tract (sputum n=14, bronchoscopy n=3, tissue n=1). Ten (55.6%) of the MDR-TB-positive sputum specimens were smear-positive, as was a single sample from a lymph node. Ten patients with MDR-TB were Papua New Guinea (PNG) nationals in the Torres Strait Protected Zone. If these PNG nationals are excluded from the analysis, the underlying MDR-TB rate in Australia was 1.4%. No cases of extensively drug-resistant TB (defined as MDR-TB with additional resistance to a fluoroquinolone and an injectable agent) were detected in 2011.

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2010. A report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collects and analyses laboratory data on new cases of disease caused by the Mycobacterium tuberculosis complex. In 2010, a total of 1,051 cases were identified by bacteriology; an annual reporting rate of 4.7 cases per 100,000 population. Twelve children aged less than 10 years had bacteriologically-confirmed tuberculosis. Results of in vitro drug susceptibility testing were available for 1,050 isolates for isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PYZ). A total of 126 (12%) isolates of M. tuberculosis were resistant to at least one of these anti-tuberculosis agents. Resistance to at least INH and RIF (defined as multi-drug resistance, MDR) was detected in 37 (3.5%) isolates, including three Australians with extensive travel in high burden TB countries; 33 were from the respiratory tract (sputum n=28, bronchoscopy n=5). Nineteen (65.5%) of the MDR-TB-positive sputum specimens were smear-positive, as were single samples from bronchoscopy and urine. Sixteen patients with MDR-TB were from the Torres Strait Protected Zone. If these Papa New Guinea nationals are excluded from the analysis, the underlying MDR-TB rate in Australian isolates was 2.0%. One case of extensively drug-resistant TB (defined as MDR-TB with additional resistance to a fluoroquinolone and an injectable agent) was detected in 2010.

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2008 and 2009. A report of the Australian Mycobacterium Reference Laboratory Network.

There were 886 and 1,062 bacteriologically-confirmed cases of tuberculosis (TB) in 2008 and 2009, representing an annual rate of 4.1 and 4.9 cases per 100,000 population respectively. Over the 2 years, a total of 23 children aged under 10 years (male n = 13, female n = 10) had bacteriologically confirmed tuberculosis, including 3 children with TB meningitis. Results of in vitro drug susceptibility testing were available for 885 of 886 and 1,060 of 1,062 isolates for isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PYZ) in 2008 and 2009 respectively. In 2008, a total of 94 (10.7%) isolates of Mycobacterium tuberculosis complex were resistant to at least one of the anti-tuberculosis agents. Any resistance to INH was noted for 76 (8.7%), 23 (2.6%) for RIF, 10 (1.1%) for EMB and 9 (1.0%) for PYZ. Resistance to at least INH and RIF (defined as multidrug-resistant TB (MDR-TB) was detected in 21 (2.4%) isolates. None of the 21 MDR-TB isolates had resistance to either ofloxacin or the injectable agents. In 2009, a total of 168 (15.9%) were resistant to at least one of the anti-TB agents. Any resistance to INH was noted for 150 (14.2%) isolates, 37 (3.5%) for RIF, 5 (0.5%) for EMB and 13 (1.2%) for PYZ. A total of 31 (2.9%) isolates were MDR-TB. In 2009, there were 2 cases of quinolone resistance in MDR-TB from persons born overseas. Mono-resistance to INH was the most commonly detected resistance with 33 and 80 isolates in 2008 and 2009, respectively. Mono-resistance to RIF was infrequently encountered with 2 and 5 isolates in 2008 and 2009 respectively. There were six and 11 MDR-TB patients from the Papua New Guinea (PNG) - Torres Strait Islands (TSI) cross-border region in 2008 and 2009 respectively. The PNG-TSI zone now contributes a substantial proportion of MDR-TB cases to the database. In addition, there were 24 isolates of Mycobacterium bovis bacille Calmette Guérin (BCG), 15 were cultured from males (4 aged < or = 5 years) and from 9 females (5 aged < or = 5 years). The predominant site of isolation was from vaccination abscess. Eight males (range: 57-87 years) had M. bovis BCG isolated from urine or blood culture.

Multiplex amplified nominal tandem-repeat analysis (MANTRA), a rapid method for genotyping Mycobacterium tuberculosis by use of multiplex PCR and a microfluidic laboratory chip.

A variable-number tandem-repeat genotyping method for Mycobacterium tuberculosis was converted to run in a multiplex PCR format on a 12-well microfluidic laboratory chip. Epidemiologically and genotypically distinct isolate clusters of M. tuberculosis were identified. This rapid genotyping method has potential application in smaller clinical laboratories and public health field investigations.

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2007. A report of the Australian Mycobacterium Reference Laboratory Network.

The Australian Mycobacterium Reference Laboratory Network collects and analyses laboratory data on new cases of disease caused by the Mycobacterium tuberculosis complex. In 2007, a total of 872 cases were identified by bacteriology; an annual reporting rate of 4.1 cases per 100,000 population. Isolates were identified as M. tuberculosis (n=867), M. africanum (n=4) and M. bovis (n=1). Fifteen children aged under 10 years had bacteriologically-confirmed tuberculosis. Results of in vitro drug susceptibility testing were available for 871 of 872 isolates for isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z). A total of 98 (11.3%) isolates of M. tuberculosis were resistant to at least one of these anti-tuberculosis agents. Resistance to at least H and R (defined as multi-drug resistance, MDR) was detected in 24 (2.8%) isolates, all from overseas-born patients; 17 were from the respiratory tract (sputum n=16, endotracheal aspirate n=1). Thirteen patients with MDR-TB were from the Papua New Guinea-Torres Strait Islands zone. Of the 98 M. tuberculosis isolates resistant to at least one of the standard drugs, 54 (55.1%) were from new cases, 9 (9.2%) from previously treated cases, and no information was available on the remaining 35 cases. Seven were Australian-born, 90 were overseas- born, and the country of birth of 1 was unknown. Of the 90 overseas-born persons with drug resistant disease, 66 (73.3%) were from 5 countries: India (n=16); Papua New Guinea (n=15); the Philippines (n=12); Vietnam (n=12); and China (n=11). No XDR-TB was detected in 2007.

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2006 a report of the Australian Mycobacterium Reference Laboratory Network.

In 2006, the Australian Mycobacterium Reference Laboratory Network identified 905 bacteriologically confirmed cases of disease caused by members of the Mycobacterium tuberculosis complex. The annual reporting rate was 4.4 cases per 100,000 population. Of the 905 isolates, 903 were Mycobacterium tuberculosis and two were Mycobacterium bovis. Fourteen children aged under 10 years (male n = 5, female n = 9) had bacteriologically confirmed tuberculosis. A total of 100 (11.1%) isolates of M. tuberculosis were resistant to at least one first-line anti-tuberculosis agent. Resistance to at least H and R (defined as multi-drug resistant--MDR) was detected in 22 (2.4%) M. tuberculosis isolates. Of the 22 MDR-TB isolates, 17 were from the respiratory tract (sputum n = 11 bronchoscopy n = 5, nasogastric aspirate n = 1), three from lymph node, one from a sacral mass, and one sterile site fluid. Smear-positive specimens from the MDR-TB cases were found in sputum (n = 6), lymph node (n = 2), and one each of bronchoscopy and nasogastric aspirate specimens. The country of birth was known for all 100 cases with a drug-resistant isolate; 10 of whom were born in Australia. The 90 overseas-born cases with drug-resistant disease were from 27 countries. Two Australian-born cases had MDR-TB; one had worked extensively in the Philippines; the other was a contact of a known MDR-TB case. No cases of extensively drug-resistant TB (XDR-TB) were identified in 2006. However, an on-going review of laboratory data identified one case of XDR-TB in 2004.

Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance, 2005.

The Australian Mycobacterium Reference Laboratory Network (AMRLN) collects and analyses laboratory data on new cases of disease caused by the Mycobacterium tuberculosis complex. In 2005, a total of 810 cases were identified by bacteriology; an annual reporting rate of 4.0 cases per 100,000 population. Isolates were identified as M. tuberculosis (n = 806), Mycobacterium africanum (n = 2) and Mycobacterium bovis (n = 2). Fifteen children aged under 10 years had bacteriologically-confirmed tuberculosis. Results of in vitro drug susceptibility testing were available for all 810 isolates for isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z). A total of 74 (9.1%) isolates of M. tuberculosis were resistant to at least one of these anti-tuberculosis agents. Resistance to at least H and R (defined as multi-drug resistance, MDR) was detected in 12 (1.5%) isolates; nine were from the respiratory tract (sputum n = 8, bronchoscopy n = 1). Of the 74 M. tuberculosis isolates resistant to at least one of the standard drugs, 67 (90.5%) were from new cases, 6 from previously treated cases, and no information was available on the remaining case. Eight were Australian-born, 65 were overseas-born, and the country of birth of one was unknown. Of the 65 overseas-born persons with drug resistant disease, 41 (63.1%) were from 4 countries; Vietnam (n = 16), Papua New Guinea (n = 10), the Philippines (n = 9), and India (n = 6). A retrospective review of AMRLN data on isolates collected between 2000 and 2005 found that none of 70 MDR-TB isolates met the new definition for extensively drug resistant TB (XDR-TB, i.e. MDR-TB with additional resistance to quinolones and second-line injectable agents).