Rapidly Growing Mycobacteria Infections Research Articles

Prevalence of rapidly growing mycobacteria (RGM) in Iran: Systematic review and meta-analysis

BackgroundThe infections due to rapidly growing mycobacteria (RGM) are becoming an important health problem in many countries in the world. Globally, an increase in RGM infections is being reported from several regions worldwide. However, there is limited information about the prevalence of these kinds of organisms in Iran. MethodsThe relevant data of the prevalence of RGM were retrieved by searching several databases, such as PubMed, Web of Science, Cochrane Library, Embase, Scopus, Iranmedex, and Scientific Information Database. Meta-analysis was performed by Comprehensive Meta-Analysis (V2.0, Biostat) software. ResultsThe meta-analyses showed that the Mycobacterium fortuitum (22.7% [95% CI 16.1–30.9]), Mycobacterium abscessus (14.0% [95% CI 6.4–27.8]) and Mycobacterium chelonae (7.6% [95% CI 2.8–18.8]) were the most prevalent RGM among the conducted studies in Iran. ConclusionsThe relatively high prevalence of RGM underlines the need for greater enforcement of infection control strategies. Establishment of appropriate diagnostic criteria and management guidelines for diseases caused by RGM and expanding the number and quality of regional reference laboratories may facilitate more accurate action for prevention and control of this kind of bacteria.

Localized cutaneous infections in immunocompetent individuals due to rapidly growing mycobacteria.

Rapidly growing mycobacteria (RGM) cause skin infections that are refractory to standard antibiotic regimens. Although typically associated with disseminated cutaneous or other systemic infections in immunocompromised patients, RGM sometimes cause localized cutaneous infections in immunocompetent hosts. These infections are almost always associated with precedent skin trauma and inoculation, and therefore have been implicated in outbreaks involving contaminated tattoo ink and inadequately sterilized acupuncture needles. Histologic features often include suppurative granulomatous inflammation, and microorganisms are rarely visualized with stains for acid-fast bacilli. The differential diagnosis includes granulomatous fungal and non-RGM bacterial infections as well as noninfectious suppurative or sarcoidlike conditions. Because no pathognomonic histologic features exist for cutaneous RGM infections, clinical suspicion and appropriate workup are essential to reach an accurate and timely diagnosis. Most localized cutaneous RGM infections in immunocompetent individuals respond well to either clarithromycin or amikacin, in combination with surgical debridement.

Infections Caused by Rapidly Growing Mycobacteria spp in Children and Adolescents With Cancer.

Rapidly growing mycobacteria (RGM) infections in pediatric oncology patients have not been completely characterized. We reviewed medical records of oncology patients at St. Jude Children's Research Hospital (St. Jude) from 1990 to 2010 with RGM infections and summarized the results of previously published cases. Twenty-five St. Jude patients had 27 episodes of infection. Approximately half of the cases occurred in patients with hematological malignancies and in males; infections were more common in white patients. Most patients were not neutropenic or lymphopenic. The most common causative species were Mycobacterium chelonae, Mycobacterium abscessus, and Mycobacterium fortuitum. Most isolates were susceptible to amikacin and clarithromycin; all were susceptible to at least 1 of these. Treatment regimens varied considerably, particularly with respect to the duration of antimicrobial chemotherapy. Two St. Jude patients died; both had pulmonary infections. The literature search identified an additional 58 cases of infection. Localized catheter-associated infections were more common than bloodstream infections in the current series than in previous reports, and outbreaks were not recognized. Otherwise, the demographic and clinical characteristics of patients were similar. Localized catheter-associated infections were most common in this largest reported single center experience reported to date. Pulmonary infection is uncommon in children but, as in adults, has a high mortality rate. Relatively short-term antimicrobial treatment and surgical debridement of infected tissue, if present, may be as effective for catheter-associated infections as prolonged antimicrobial use and may reduce adverse drug effects in these patients, who are vulnerable to drug-drug interactions and toxicity.

The clinical management of cesarean section-acquired Mycobacterium abscessus surgical site infections

Rapidly growing mycobacteria (RGM) can cause a broad spectrum of both community and healthcare-associated infections in humans. The aim of this study was to report the clinical management and outcomes of successive patients following cesarean delivery with healthcare-associated surgical site infections (SSIs) caused by RGM. Patients who were admitted to Chung Shan Medical University Hospital, Taichung, Taiwan, between September 2006 and July 2008, and who developed SSIs following cesarean delivery at an obstetrics hospital and were then referred to our hospital, were enrolled. Demographic characteristics of the patients and clinical isolates were obtained retrospectively and an environmental investigation was performed. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the hsp65gene and pulsed-field gel electrophoresis (PFGE) of large genomic DNA restriction fragments were applied to differentiate Mycobacterium species. Seventeen patients were diagnosed with RGM infections by microbiology and/or histopathology. Mycobacterial isolates by PCR-RFLP analysis from 15 patients revealed Mycobacterium abscessus (M. abscessus) and M. lentiflavum. Most of the patients received surgical debridement and combination antimicrobial therapy and were eventually cured. Our study demonstrates the potential that RGM infections have in causing healthcare-associated SSIs. Surgery plus prolonged combination antimicrobial therapy seemed to be an effective option for the management of M. abscessus infections.

Management of Infections with Rapidly Growing Mycobacteria after Unexpected Complications of Skin and Subcutaneous Surgical Procedures

BackgroundInfection caused by rapidly growing mycobacteria (RGM) is not uncommon, and the prevalence of RGM infection has been increasing. Clinical diagnosis is difficult because there are no characteristic clinical features. There is also no standard antibiotic regimen for treating RGM infection. A small series of patients with RGM infections was studied to examine their treatments and outcomes.MethodsA total of 5 patients who had developed postoperative infections from January 2009 to December 2010 were retrospectively reviewed. Patients were initially screened using a mycobacteria rapid screening test (polymerase chain reaction [PCR]-reverse blot hybridization assay). To confirm mycobacterial infection, specimens were cultured for nontuberculous mycobacteria and analyzed by 16 S ribosomal RNA and rpoB gene PCR.ResultsThe patients were treated with intravenous antibiotics during hospitalization, and oral antibiotics were administered after discharge. The mean duration of follow-up was 9 months, and all patients were completely cured of infection with a regimen of a combination of antibiotics plus surgical treatment. Although none of the patients developed recurrence, there were complications at the site of infection, including hypertrophic scarring, pigmentation, and disfigurement.ConclusionsCombination antibiotic therapy plus drainage of surgical abscesses appeared to be effective for the RGM infections seen in our patients. Although neither the exact dosage nor a standardized regimen has been firmly established, we propose that our treatment can provide an option for the management of rapidly growing mycobacterial infection.

Infecciones por micobacterias de crecimiento rápido

Rapidly growing mycobacteria (RGM) are ubiquitous in nature and widely distributed in water, soil and animals. During the past three decades we have observed a notable increment of infections caused by RGM, both localized and disseminated, as well as nosocomial outbreaks of contaminated medical equipment. The microbiological diagnosis of RGM infections includes direct microscopic observation and culture. The taxonomic identification is performed by phenotypic, biochemical, chromatographic and molecular biology techniques. The treatment differs from that of other mycobacteriosis like tuberculosis, owing to the variable in vitro susceptibility of the species of this group. The RGM are resistant to conventional antituberculous drugs, but can be susceptible to broad spectrum antimicrobial agents. In this study we comment on the significant aspects of human infections by RGM, including their biology, epidemiology, pathology, microbiological diagnosis, taxonomic identification, antimicrobial susceptibility and treatment.

Phenotypic and molecular characterization of quinolone resistance in Mycobacterium abscessus subsp. bolletii recovered from postsurgical infections

Several outbreaks of infections caused by rapidly growing mycobacteria (RGM) were reported in many Brazilian states (2032 notified cases) from 2004 to 2010. Most of the confirmed cases were mainly associated with Mycobacterium massiliense (recently renamed as Mycobacterium abscessus subsp. bolletii) BRA100 clone, recovered from patients who had undergone invasive procedures in which medical instruments had not been properly sterilized and/or disinfected. Since quinolones have been an option for the treatment of general RGM infections and have been suggested for therapeutic schemes for these outbreaks, we evaluated the in vitro activities of all generations of quinolones for clinical and reference RGM by broth microdilution, and analysed the peptide sequences of the quinolone resistance determining regions (QRDRs) of GyrA and GyrB after DNA sequencing followed by amino acid translation. Fifty-four isolates of M. abscessus subsp. bolletii, including clone BRA100, recovered in different states of Brazil, and 19 reference strains of RGM species were characterized. All 54 M. abscessus subsp. bolletii isolates were resistant to all generations of quinolones and showed the same amino acids in the QRDRs, including the Ala-83 in GyrA, and Arg-447 and Asp-464 in GyrB, described as being responsible for an intrinsic low level of resistance to quinolones in mycobacteria. However, other RGM species showed distinct susceptibilities to this class of antimicrobials and patterns of mutations contrary to what has been traditionally defined, suggesting that other mechanisms of resistance, different from gyrA or gyrB mutations, may also be involved in resistance to high levels of quinolones.

Susceptibility of rapidly growing mycobacteria and Nocardia isolates from cats and dogs to pradofloxacin

Rapidly growing mycobacteria (RGM) and Nocardiae can cause severe or refractory infections in cats and dogs. Prolonged antibacterial therapy is required to cure these infections. As fluoroquinolones have been used in combination therapy for treating RGM infections, isolates from the Mycobacterium smegmatis cluster ( n = 64), Mycobacterium fortuitum cluster ( n = 17), and M. mageritense cluster ( n = 2), collected from feline and canine patients, underwent susceptibility testing to pradofloxacin. The MIC 50, MIC 90 and tentative epidemiological cut-off (ECOFF) values as determined by microbroth dilution susceptibility testing that inhibited growth of the M. smegmatis and M. fortuitum clusters were 0.063, 0.125 and ≤0.25; and 0.125, 0.250 and ≤1.0 μg/mL, respectively. E-Test results showed similar trends but MICs were lower than those for microbroth dilution. In summary, pradofloxacin demonstrated effective in vitro activity against RGM isolates. Additionally, veterinary isolates of Nocardia nova ( n = 18), Nocardia farcinica ( n = 3) and Nocardia cyriacigeorgica ( n = 1) underwent microbroth dilution testing to ciprofloxacin, enrofloxacin and pradofloxacin. The MIC 50 and MIC 90 of pradofloxacin, ciprofloxacin and enrofloxacin that inhibited growth of Nocardia nova isolates were 2 (4), 8 (16), 16 (32) μg/mL, respectively. The tentative ECOFF values for pradofloxacin and ciprofloxacin were 32 μg/mL and for enrofloxacin 64 μg/mL. The MIC or MIC range for the three N. farcinica isolates of pradofloxacin, ciprofloxacin and enrofloxacin were 0.25–0.5, 2 and 2 μg/mL and for the single N. cyriacigeorgica isolate were 1, 4 and 4 μg/mL, respectively. On the basis on these results, fluoroquinolones appear to have limited therapeutic potential for most Nocardia infections.

Susceptibility of rapidly growing mycobacteria isolated from cats and dogs, to ciprofloxacin, enrofloxacin and moxifloxacin

Rapidly growing mycobacteria (RGM) cause infections in cats and dogs which require prolonged antibacterial medication for resolution. In Australia, pathogens from the Mycobacterium fortuitum and Mycobacterium smegmatis clusters are responsible for most of the RGM infections in cats and dogs. As fluoroquinolones are often recommended for treating such infections, 14 M. fortuitum isolates, 51 isolates from the M. smegmatis cluster and 2 M. mageritense isolates, collected from feline and canine patients, underwent susceptibility testing to the second generation fluoroquinolones ciprofloxacin and enrofloxacin and the newer generation fluoroquinolone moxifloxacin. Using microbroth dilution, the MIC90 of ciprofloxacin, enrofloxacin, and moxifloxacin that inhibited growth of M. fortuitum isolates were 0.500, 0.250 and 0.063μg/mL respectively. For the M. smegmatis cluster isolates the corresponding MIC90 was 0.500, 0.250 and 0.125μg/mL respectively. E-test results showed similar trends but MICs were lower than those determined by microbroth dilution. Additionally, moxifloxacin was administered to 10 clinically normal cats (50mg per cat, once daily for 4 days). The plasma moxifloxacin concentration 2h after the last dose was determined by liquid chromatography as 2.2±0.6μg/mL. The plasma concentration at 2h:MIC90 ratios for moxifloxacin for M. fortuitum and M. smegmatis cluster was 34.9 and 17.6 respectively which exceeded the recommended threshold of 10, indicating that moxifloxacin has good theoretical efficacy for treatment of those M. fortuitum and M. smegmatis infections in cats and dogs that have become refractory to other antibacterial drug classes.

High efficacy of clofazimine and its synergistic effect with amikacin against rapidly growing mycobacteria

The aim of this study was to determine whether clofazimine, dapsone and cycloserine may be suitable antimicrobial agents for the treatment of infections due to rapidly growing mycobacteria (RGM). The antimicrobial activity of the three drugs against 117 Mycobacterium abscessus isolates, 48 Mycobacterium fortuitum isolates and 20 Mycobacterium chelonae isolates was evaluated based on their broth microdilution minimal inhibitory concentrations (MICs) against the isolates. Clofazimine was highly efficacious against these RGM. The vast majority of M. abscessus, M. fortuitum and M. chelonae isolates (99.1%, 91.7% and 100%, respectively) had clofazimine MICs of ≤1 mg/L. MIC 50 values (MIC for 50% of the organisms) of clofazimine against the isolates ranged from 0.25 mg/L to 0.5 mg/L and MIC 90 values (MIC for 90% of the organisms) ranged from 0.5 mg/L to 1.0 mg/L. Cycloserine and dapsone had little or no activity against the isolates. The effects of combined application of clofazimine and amikacin on 40 M. abscessus isolates, 48 M. fortuitum isolates and 20 M. chelonae isolates were evaluated. Addition of 0.25× MIC of amikacin for the isolates to clofazimine reduced clofazimine MICs in all of the M. abscessus and M. chelonae isolates and in 48% of the M. fortuitum isolates tested. Clofazimine, either alone or combined with amikacin, may serve as a promising drug for the treatment of RGM infections.

Host Immune Response to Rapidly Growing Mycobacteria, an Emerging Cause of Chronic Lung Disease

Rapidly growing mycobacteria (RGM) are environmental organisms classified under the broader category of nontuberculous mycobacteria. The most common RGM to cause human diseases are Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium massiliense. Infections due to the RGM are an emerging health problem in the United States. Chronic pulmonary disease and skin/soft-tissue infections are the two most common disorders due to these organisms. Clinical outcomes in the treatment of M. abscessus infections are generally disappointing. Because less is known about the nature of the immune response to M. abscessus than for tuberculosis, we herein highlight the major clinical features associated with infections due to M. abscessus and other RGM, and review the known host immune response to RGM, drawing from experimental animal and clinical studies. Based on in vitro and in vivo murine models, Toll-like receptor 2, dectin-1, tumor necrosis factor (TNF)-α, IFN-γ, leptin, T cells, and possibly neutrophils are important components in the host defense against RGM infections. However, excessive induction of TNF-α by the R morphotype of M. abscessus may allow it to be more pathogenic than the S morphotype. Clinical observations and/or genetic studies in humans corroborate many of the findings in animals in that those with cell-mediated immunodeficiency, genetic defects in IFN-γ-IL-12 axis, and those individuals on TNF-α blockers are at increased risk for nontuberculous mycobacteria infections, including the RGM. However, much remains to be discovered on why seemingly healthy individuals, particularly slender postmenopausal women with thoracic cage anomalies, appear to be at increased risk.

Infecções por micobactérias de crescimento rápido resistentes a desinfetantes: uma problemática nacional?

Rapidly growing mycobacteria (RGM) are opportunistic microorganisms and widely distributed into aqueous environment and soil. Human RGM infections are usually associated with contaminated solutions or medical instruments used during invasive procedures. RGM postsurgical infections have recently emerged in Brazil and have caused national alert, considering the risk factors and epidemiological aspects. This study aimed at analysing the main factors linked to the recent RGM outbreaks, with focus on the national epidemic of Mycobacterium massiliense infections related to the BRA100 strains resistant to 2% glutaraldehyde commercial solutions commonly used for preoperative high-level disinfection. Based on previous studies and laboratorial results of assays and colaborations, it has been observed that the cases have been associated with videolaparoscopy for different applications and elective esthetic procedures, such as lipoaspiration and mammary prosthesis implant. Furthermore, outbreaks between 2004 and 2008 and the epidemic in Rio de Janeiro state may be considered particular Brazilian events. Although there are a few epidemiological published studies, some hypotheses based on common aspects related to most national nosocomial occurrences are possible, such as lack of protocols for cleaning and high-level disinfection, use of 2% glutaraldehyde as high-level disinfectant for surgical instruments, and dissemination of M. massiliense BRA100 by unknown mechanisms.

Diagnosis and Treatment of Infections Caused by Rapidly Growing Mycobacteria

Rapidly growing mycobacteria (RGM) are ubiquitous environmental organisms capable of causing a wide variety of infections in humans. The prevalence of RGM infections appears to be increasing, although exact incidence rates are unknown. Although some risk factors for pulmonary RGM infection have been determined, the specific host factors predisposing to disease in the majority of cases are not clear. Significant advances in molecular methods of mycobacterial identification have led to isolation of more varieties, changes in taxonomy, and more rapid and accurate diagnosis of RGM from clinical isolates. Despite significant advances in the field, diagnosing and treating RGM pulmonary infections remain complicated. Current guidelines are based on the most commonly encountered NTM. Their applicability to less frequent RGM isolates has not been definitively established. Treatment often requires multiple antimicrobial agents for prolonged periods of time, with varying degrees of success and significant associated morbidity.

Mycobacterium barrassiae sp. nov., a Mycobacterium moriokaense Group Species Associated with Chronic Pneumonia

Three identical isolates of new rapidly growing mycobacteria (RGM) were recovered from the bronchial aspirate and sputum from a 49-year-old woman presenting with lung lesions. The case met the American Thoracic Society criteria for the diagnosis of nontuberculous mycobacterial infection. The three isolates grew in 3 days at 24 to 42 degrees C. The 16S rRNA gene sequence analysis indicated that the sequences of the isolates were identical and shared 99.7% and 98.1% similarities with those of Mycobacterium moriokaense and Mycobacterium gadium, respectively. Partial 723-bp rpoB sequence analyses indicated that the sequences of the isolates shared 95.8% and 92.3% similarities with those of M. moriokaense and M. gadium, respectively. Polyphasic identification (including biochemical tests; antimicrobial susceptibility profiling; and hsp65, recA, and sodA gene sequence analyses, as well as G+C content determination and cell wall fatty acid composition analysis) supported the evidence that these isolates were representative of a new species. Phylogenetic analyses confirmed the close relationships of the isolates with M. moriokaense and the defined M. moriokaense group. These isolates were susceptible to the antimicrobials currently recommended for the treatment of RGM infections. These isolates differed from M. moriokaense by their susceptibility to vancomycin. We propose the name Mycobacterium barrassiae sp. nov. for this new species. The type strain is N7T (CIP 108545T and CCUG 50398T).

RpoB gene sequence-based characterization of emerging non-tuberculous mycobacteria with descriptions of Mycobacterium bolletii sp. nov., Mycobacterium phocaicum sp. nov. and Mycobacterium aubagnense sp. nov.

Over the past 10 years, 16S rRNA gene sequencing has contributed to the establishment of more than 45 novel species of non-tuberculous mycobacteria and to the description of emerging mycobacterial infections. Cumulative experience has indicated that this molecular tool underestimates the diversity of this group and does not distinguish between all recognized mycobacterial taxa. In order to improve the recognition of emerging rapidly growing mycobacteria (RGM), rpoB gene sequencing has been developed. Our previous studies have shown that an RGM isolate is a member of a novel species if it exhibits >3 % sequence divergence in the rpoB gene from the type strains of established species. When applied to a collection of 59 clinical RGM isolates, rpoB gene sequencing revealed nine novel isolates (15.3 %) whereas only two isolates (3.4 %) were deemed to be novel by conventional 16S rRNA gene sequence analysis. A polyphasic approach, including biochemical tests, antimicrobial susceptibility analyses, hsp65, sodA and recA gene sequence analysis, DNA G+C content determination and cell-wall fatty acid composition analysis, supported the evidence that these nine isolates represent three novel species. Whereas Mycobacterium phocaicum sp. nov. (type strain N4T = CIP 108542T = CCUG 50185T) and Mycobacterium aubagnense sp. nov. (type strain U8T = CIP 108543T = CCUG 50186T; Mycobacterium mucogenicum group) were susceptible to most antibiotics, Mycobacterium bolletii sp. nov. (type strain BD(T) = CIP 108541T = CCUG 50184T; Mycobacterium chelonae-abscessus group) was resistant to the quinolones, tetracycline, macrolides and imipenem. Only M. bolletii was resistant to clarithromycin. These data illustrate that rpoB gene sequence-based identification is a powerful tool to characterize emerging RGM and mycobacterial infections and provides valuable help in differentiating RGM at both the intra- and interspecies level, thus contributing to a faster and more efficient diagnosis and epidemiological follow-up.