zithromax and Mycobacterium-Infections

Mycobacterium abscessus is an emerging mycobacteria that is responsible for lung diseases and healthcare-associated extrapulmonary infections. Recent findings support its taxonomic status as a single species comprising 3 subspecies designated abscessus, bolletii and massiliense. We performed a review of English-language publications investigating all three of these subspecies. Areas covered: Worldwide, human infections are often attributable to environmental contamination, although the isolation of M. abscessus in this reservoir is very rare. Basic research has demonstrated an association between virulence and cell wall components and cording, and genome analysis has identified gene transfer from other bacteria. The bacteriological diagnosis of M. abscessus is based on innovative tools combining molecular biology and mass spectrometry. Genotypic and phenotypic susceptibility testing are required to predict the success of macrolide (clarithromycin or azithromycin)-based therapeutic regimens. Genotyping methods are helpful to assess relapse and cross-transmission and to search for a common source. Treatment is not standardised, and outcomes are often unsatisfactory. Expert commentary: M. abscessus is still an open field in terms of clinical and bacteriological research. Further knowledge of its ecology and transmission routes, as well as host-pathogen interactions, is required. Because the number of human cases is increasing, it is also necessary to identify more active treatments and perform clinical trials to assess standard effective regimens.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Cystic Fibrosis; Humans; Mycobacterium; Mycobacterium Infections; Prevalence; Respiratory Tract Infections; Treatment Outcome; Virulence

Mycobacterium abscessus is the most pathogenic and chemotherapy-resistant rapid-growing mycobacterium. It is commonly associated with contaminated traumatic skin wounds and with post-surgical soft tissue infections. It is also one of the mycobacteria that are most often isolated from cystic fibrosis patients. It is essential to differentiate this species from the formerly indistinct "M. chelonae-complex", as chemotherapy is especially difficult in M. abscessussenso strictu. Clarithromycin or azithromycin are the only regular oral antimycobacterial agents with an effect on M. abscessus, and should preferably be supplemented with other drugs since long-term monotherapy may cause resistance. Amikacin is a major parenteral drug against M. abscessus that should also be given in combination with another drug. The recently introduced drug tigecycline may prove to be an important addition to chemotherapy, but has yet to be fully clinically evaluated as an antimycobacterial agent. Surgery can be curative, or at least helpful, in the healing of M. abscessus infection, and if conducted, it should include the removal of all foreign or necrotic material. There is increasing awareness of M. abscessus as an emerging pathogen.

Topics: Administration, Oral; Amikacin; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Cystic Fibrosis; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Minocycline; Mycobacterium; Mycobacterium Infections; Respiratory Tract Infections; Skin; Soft Tissue Infections; Species Specificity; Surgical Wound Infection; Tigecycline; Tuberculosis, Cutaneous; Wounds and Injuries

Approximately 21 human cases of infection with Mycobacterium conceptionense have been reported. However, most cases were outside the United States, and optimal treatment remains uncertain. We report a case of M. conceptionense pneumonitis in a patient with HIV/AIDS in the United States. The patient was cured with azithromycin and doxycycline.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Azithromycin; Doxycycline; Drug Therapy, Combination; Humans; Male; Middle Aged; Mycobacteriaceae; Mycobacterium Infections; Pneumonia; United States

Mycobacterium abscessus subsp. massiliense (a subspecies of the M. abscessus complex) is a rare causative agent of surgical site infection after cesarean section (C section). We tried to seek the common source of infection and unravel the optimal treatment modalities.. From September 2009 to October 2012, four postpartum women developed C-section wound infections caused by M. massiliense. Speciation of the four isolates was identified using of hsp65, rpoB, and secA1 partial gene sequencing and the Basic Local Alignment Search Tool. The erm(41) and rrl genes were detected for the possibility of inducible macrolide resistance. Pulsed-field gel electrophoresis was used as a tool of molecular epidemiology. All patients underwent intensive intravenous and oral antimycobacterial regimens. Of these patients, three underwent debridement at least once.. All four isolates were identified as M. abscessus subsp. massiliense. All of the isolates harbored a truncated erm(41) gene without rrl gene mutations, which explains the susceptibility to clarithromycin and azithromycin. Three isolates were indistinguishable by DNA strain typing, and the fourth strain was clonal with the other three strains. Their infections were not improved in spite of teicoplanin treatment initially. These patients underwent antimycobacterial regimens with/without surgery and were all cured.. Teicoplanin treatment failure, painful cutaneous nodules, and persistent wound drainage alerted us to the possibility of nontuberculous mycobacterial skin and soft tissue infection. Accurate identification of subspecies, detection of drug resistance genes, susceptibility testing, and optimal antimycobacterial agents with/without surgical debridement are warranted for successful treatment.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Cesarean Section; Chaperonin 60; Cilastatin; Cilastatin, Imipenem Drug Combination; Clarithromycin; Drug Combinations; Electrophoresis, Gel, Pulsed-Field; Female; Fluoroquinolones; Humans; Imipenem; Methyltransferases; Microbial Sensitivity Tests; Molecular Typing; Moxifloxacin; Mycobacterium Infections; Nontuberculous Mycobacteria; Pregnancy; Surgical Wound Infection; Teicoplanin

Of the non-tuberculous mycobacteria, Mycobacterium abscessus is particularly refractory to antimicrobial therapy and new agents with activity against these pathogens are urgently needed. The screening of candidate antimicrobial agents against M. abscessus requires a relevant and reproducible animal model of chronic infection. Granulocyte-macrophage colony-stimulating factor knockout (GM-CSF KO) mice were used to develop a new animal model of chronic pulmonary M. abscessus infection that can be used for preclinical efficacy testing of antimicrobial drugs.. GM-CSF KO mice were infected with a clinical isolate of M. abscessus via intrapulmonary aerosol delivery using a microsprayer device. The clinical condition, histology and cfu of M. abscessus-infected GM-CSF KO mice were evaluated over a period of 4 months. Mice were treated with azithromycin (100 mg/kg) by oral gavage and the clinical condition, histology and bacterial burden was determined after 2 weeks of treatment.. We show that pulmonary infection of GM-CSF KO mice with M. abscessus results in a chronic pulmonary infection that lends itself to preclinical testing of new antimicrobial drugs against this bacterium. Azithromycin treatment of M. abscessus-infected GM-CSF KO mice resulted in a lower bacterial burden in the lungs and spleen, weight gain and significant improvement in lung pathology.. Intrapulmonary aerosol infection of GM-CSF KO mice with M. abscessus is a useful animal model for studying pathogenesis as well as pre-clinical testing of new compounds against M. abscessus in acute or chronic phases of infection.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Load; Chronic Disease; Disease Models, Animal; Drug Evaluation, Preclinical; Granulocyte-Macrophage Colony-Stimulating Factor; Histocytochemistry; Lung; Mice; Mice, Knockout; Mycobacterium; Mycobacterium Infections; Pneumonia, Bacterial; Spleen

A 4-year-old spayed female ferret presented with a 2-month history of anorexia, vomiting and occasional diarrhea. Abdominal ultrasonography revealed thickening of the gastric wall and enlarged abdominal lymph nodes. Biopsy samples from the thickened gastric wall, enlarged abdominal lymph nodes and liver were taken during an exploratory laparotomy. Based on the histopathological examination, mycobacterium infection was diagnosed. The bacterial species could not be identified by additional diagnostic tests of feces, including fecal smear, culture and polymerase chain reaction (PCR). The ferret was treated with prednisolone and multiple antimicrobials, including rifampicin, azithromycin and enrofloxacin, but did not improve with treatment and died 220 days after the first presentation.

Topics: Animals; Anti-Infective Agents; Azithromycin; Enrofloxacin; Fatal Outcome; Female; Ferrets; Fluoroquinolones; Hematocrit; Histological Techniques; Laparotomy; Leukocyte Count; Mycobacterium Infections; Prednisolone; Rifampin

Mycobacterium celatum is a rare cause of human infection, causing disseminated disease in immunosuppressed individuals. Infections localized to the lungs and the lymph nodes have also been reported in immunocompetent individuals. The existing literature on the subject is limited as are experiences with treatment regimens and durations. In the case presented herein, two different treatment regimens were applied to an immunocompromised HIV-negative patient with primary skin involvement and extensive pulmonary involvement due to suspected relapse on isoniazid, ethambutol, and clarithromycin treatment. The treatment regimen was changed to azithromycin, ciprofloxacin, and pyrazinamide and the treatment duration was prolonged to a total of 24 months, with good effect.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Ciprofloxacin; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Lung; Lung Diseases; Mycobacterium; Mycobacterium Infections; Pyrazinamide; Radiography

Cystic fibrosis (CF) patients are at particularly high risk of developing lung disease caused by Mycobacterium abscessus complex (MABSC). Over the last 10 years, changes in CF treatment, with increasing use of inhaled therapies and low-dose azithromycin, have been accompanied by an increase in the prevalence of MABSC infections in CF patients. There is therefore some concern about the role of new CF treatments in the emergence of MABSC infections. We addressed this issue by means of a case-control study including 30 MABSC-positive cases and 60 nontuberculous mycobacteria-negative CF controls matched for age, sex and centre. We also compared practices at the CF centres with the highest prevalence of MABSC with those at the other centres. No positive association was found between MABSC lung disease and the use of inhaled therapies or low-dose azithromycin in the 4 years preceding MABSC isolation. These treatments were not significantly more frequently used at the CF centres with the highest MABSC prevalence rates. In conclusion, there is no evidence for a link between M. abscessus complex lung disease and inhaled therapies or low-dose azithromycin in patients with CF.

Topics: Administration, Inhalation; Adolescent; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Cystic Fibrosis; Female; France; Humans; Lung Diseases; Male; Mycobacterium Infections; Nontuberculous Mycobacteria; Prevalence; Registries; Risk Factors; Young Adult

Clarithromycin was the drug of choice for Mycobacterium abscessus infections until inducible resistance due to erm(41) was described. Because M. abscessus was split into M. abscessus sensu stricto, Mycobacterium massiliense, and Mycobacterium bolletii, we looked for erm(41) in the three species and determined their clarithromycin susceptibility levels. Ninety strains were included: 87 clinical strains from cystic fibrosis patients (61%) and others (39%), representing 43 M. abscessus, 30 M. massiliense, and 14 M. bolletii strains identified on a molecular basis, and 3 reference strains. Clarithromycin and azithromycin MICs were determined by broth microdilution and Etest with a 14-day incubation period. Mutations in rrl (23S rRNA gene) known to confer acquired clarithromycin resistance were also sought. erm(41) was detected in all strains but with two deletions in all M. massiliense strains. These strains were indeed susceptible to clarithromycin (MIC(90) of 1 μg/ml) except for four strains with rrl mutations. M. abscessus strains harbored an intact erm(41) but had a T/C polymorphism at the 28th nucleotide: T28 strains (Trp10 codon) demonstrated inducible clarithromycin resistance (MIC(90) of >16 μg/ml), while C28 strains (Arg10) were susceptible (MIC(90) of 2 μg/ml) except for two strains with rrl mutations. M. bolletii strains had erm(41) sequences similar to the sequence of the T28 M. abscessus group, associated with inducible clarithromycin resistance (MIC(90) of >16 μg/ml). erm(41) sequences appeared species specific within the M. abscessus group and were fully concordant with clarithromycin susceptibility when erm(41) sequencing was associated with detection of rrl mutations. Clarithromycin-resistant strains, including the six rrl mutants, were more often isolated in cystic fibrosis patients, but this was not significantly associated with a previous treatment.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; DNA, Bacterial; Genes, rRNA; Humans; Methyltransferases; Microbial Sensitivity Tests; Molecular Sequence Data; Mycobacterium; Mycobacterium Infections; RNA, Ribosomal, 23S; Sequence Analysis, DNA

Mycobacterium bolletii and Mycobacterium massiliense are recently described species of nontuberculous mycobacteria. Footbaths preceding pedicures at nail salons have been implicated as reservoirs of infection with nontuberculous mycobacteria. To our knowledge, this case series represents the first documented outbreak of M bolletii/M massiliense furunculosis, identified by heat-shock protein 65 gene, hsp65, sequencing, occurring in immunocompetent patrons of a North Carolina nail salon.. We describe 3 cases of lower extremity furunculosis caused by M bolletii/M massiliense associated with pedicure footbaths from the same North Carolina nail salon. Lesions developed within 1 month of the salon visit and were characterized by erythematous, indurated papules and plaques. Histologic examination revealed suppurative granulomatous dermatitis. Mycobacterium bolletii/M massiliense was identified by sequencing the 16S ribosomal RNA (rRNA) and hsp65 genes. All 3 patients responded to different combinations of clarithromycin, doxycycline hydrochloride, azithromycin, and moxifloxacin hydrochloride for complete lesion resolution.. Clinicians should elicit a history of pedicure footbaths and maintain a high level of suspicion when faced with skin lesions of the lower extremities that are culture negative or are refractory to conventional antibiotic therapy. Accurate identification and discrimination of M massiliense and M bolletii is difficult and requires sequencing of multiple gene targets beyond their identical 16S rRNA sequences.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Aza Compounds; Azithromycin; Bacterial Proteins; Baths; Chaperonin 60; Cosmetic Techniques; Female; Fluoroquinolones; Foot Dermatoses; Furunculosis; Humans; Moxifloxacin; Mycobacterium; Mycobacterium Infections; Quinolines; Treatment Outcome; Young Adult

Azithromycin is a potent macrolide antibiotic with poorly understood antiinflammatory properties. Long-term use of azithromycin in patients with chronic inflammatory lung diseases, such as cystic fibrosis (CF), results in improved outcomes. Paradoxically, a recent study reported that azithromycin use in patients with CF is associated with increased infection with nontuberculous mycobacteria (NTM). Here, we confirm that long-term azithromycin use by adults with CF is associated with the development of infection with NTM, particularly the multi-drug-resistant species Mycobacterium abscessus, and identify an underlying mechanism. We found that in primary human macrophages, concentrations of azithromycin achieved during therapeutic dosing blocked autophagosome clearance by preventing lysosomal acidification, thereby impairing autophagic and phagosomal degradation. As a consequence, azithromycin treatment inhibited intracellular killing of mycobacteria within macrophages and resulted in chronic infection with NTM in mice. Our findings emphasize the essential role for autophagy in the host response to infection with NTM, reveal why chronic use of azithromycin may predispose to mycobacterial disease, and highlight the dangers of inadvertent pharmacological blockade of autophagy in patients at risk of infection with drug-resistant pathogens.

Topics: Adult; Animals; Anti-Bacterial Agents; Autophagy; Azithromycin; Chlorocebus aethiops; COS Cells; Cystic Fibrosis; Drug Resistance, Bacterial; Enzyme Inhibitors; HeLa Cells; Humans; Lysosomes; Macrolides; Macrophages; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins; Mycobacterium; Mycobacterium Infections; Phagosomes; Recombinant Fusion Proteins; Sirolimus

Tumor necrosis factor-alpha inhibitors are potent anti-rheumatic drugs, but there is evidence that the high level of immunosuppression they provide may also lead to a higher risk of infections. At our institution, 3 patients with inflammatory arthritis treated with tumor necrosis factor-alpha inhibitors developed mycobacterial soft tissue infections after routine hand surgery. All 3 patients required multiple surgical procedures, inpatient hospitalizations, and prolonged antibiotic multidrug therapy to clear the infections.

Topics: Aged; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Azithromycin; Etanercept; Female; Hand; Humans; Immunoglobulin G; Infliximab; Male; Methotrexate; Middle Aged; Mycobacterium Infections; Receptors, Tumor Necrosis Factor; Tenosynovitis; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Burn Units; Burns; Cohort Studies; Fatal Outcome; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium Infections; Tobramycin; Trachea

We evaluated the in vitro activities of tigecycline and 10 other antibiotics against clinical isolates of nonpigmented rapidly growing mycobacteria. Fifteen collection strains and 165 clinical isolates were included in the study. Tigecycline showed the highest activity among all antibiotics studied: all the strains were inhibited by 1 mg/liter.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Mycobacterium; Mycobacterium Infections; Pigmentation; Species Specificity; Tigecycline

Topics: Acquired Immunodeficiency Syndrome; Adult; Azithromycin; Colonic Diseases; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Fatal Outcome; Granular Cell Tumor; Humans; Immunocompromised Host; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections; Nucleic Acid Amplification Techniques; Rifabutin; RNA, Bacterial; Whipple Disease

To describe the clinical and laboratory features of infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a patient with Stevens-Johnson syndrome.. Case report. A 19-year-old man with a history of Stevens-Johnson syndrome and multiple corneal transplants developed white crystalline corneal infiltrates.. Anterior chamber aspirate disclosed acid-fast bacilli. A repeat corneal transplant was performed and antibiotic therapy begun. Histopathology showed focal acute inflammation surrounding collections of acid-fast bacilli, which were speciated as M. abscessus.. M. abscessus is a cause of infectious crystalline keratopathy and endophthalmitis. Risk factors include ocular surface disease, corneal transplantation, and immunosuppressive therapy.

Topics: Adult; Amikacin; Anterior Chamber; Azithromycin; Corneal Diseases; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Bacterial; Humans; Keratoplasty, Penetrating; Male; Mycobacterium; Mycobacterium Infections; Stevens-Johnson Syndrome; Vision, Monocular

The comparative activities of azithromycin (AZI) and clarithromycin (CLA) were evaluated against nontuberculous mycobacteria in a murine model of disseminated infection. Four-week-old beige mice (C57BL/6J bgj/bgj) were infected intravenously with approximately 10(7) viable Mycobacterium kansasii, M. xenopi, M. simiae, or M. malmoense. Treatment with AZI at 200 mg/kg, CLA at 200 mg/kg, ethambutol at 125 mg/kg, rifampin at 20 mg/kg, or clofazimine at 20 mg/kg of body weight was started 7 days postinfection, and the treatments were administered 5 days per week for 4 weeks. Control groups were sacrificed at the start and end of the treatments. Spleens and lungs were homogenized, and viable cell counts were determined by serial dilution and plating onto 7H10 agar. AZI and CLA had activities comparable to or better than that of rifampin, ethamutol, or clofazimine against these nontuberculous mycobacteria in the beige mouse test system. AZI at 200 mg/kg was more active than CLA at 200 mg/kg against organisms in the spleens for M. xenopi and M. malmoense. The activities of AZI and CLA were comparable against organisms in the spleens for M. kansasii and M. simiae. The activities of these two agents were comparable against organisms in the lungs for all four nontuberculous mycobacterial species. AZI or CLA in combination with other agents may be useful for the therapy of nontuberculous mycobacterial infections in humans.

Topics: Animals; Azithromycin; Clarithromycin; Culture Media; Female; Lung; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Spleen