Treatment Of Nontuberculous Mycobacterial Infections Research Articles

Pharmacotherapeutic Considerations in the Treatment of Nontuberculous Mycobacterial Infections: A Primer for Clinicians.

Nontuberculous mycobacteria (NTM) can cause a variety of infections, including serious pulmonary disease. Treatment encompasses polypharmacy, with a targeted regimen of 2-5 active medications, depending on site of infection, species, and clinical characteristics. Medications may include oral, intravenous, and inhalational routes. Medication acquisition can be challenging for numerous reasons, including investigational status, limited distribution models, and insurance prior authorization. Additionally, monitoring and managing adverse reactions and drug interactions is a unique skill set. While NTM is primarily medically managed, clinicians may not be familiar with the intricacies of medication selection, procurement, and monitoring. This review offers insights into the pharmacotherapeutic considerations of this highly complex disease state, including regimen design, medication acquisition, safety monitoring, relevant drug-drug interactions, and adverse drug reactions.

Nontuberculous Mycobacterial Infections in Pediatric Solid Organ Transplant and Hematopoietic Cell Transplant Recipients.

The diagnosis of nontuberculous mycobacterial infections is challenging in pediatric solid organ transplant and hematopoietic cell transplant recipients due to the absence of specific clinical manifestations, limitations of sampling, prolonged times for culture and identification, and difficulty discerning colonization from clinical disease. Treatment is dependent on the nontuberculous mycobacterial species, disease type, and pattern of drug resistance. Treatment of nontuberculous mycobacterial infections involves prolonged durations of therapy using multiple medications, which are limited by toxicities and drug-drug interactions.

Efficacy of Bortezomib for Treating Anti-Interferon-Gamma Autoantibody-Associated Adult-Onset Immunodeficiency Syndrome.

Currently, there is no effective treatment for adult-onset immunodeficiency (AOID) syndrome with anti-interferon-gamma autoantibodies (anti-IFN-γ-auto-Abs). This study aimed to investigate the effectiveness of bortezomib (BTZ) for decreasing anti-IFN-γ-auto-Abs. A pre- and post-intervention study was conducted from February 2017 through June 2019 at Siriraj Hospital (Bangkok, Thailand). Five patients were invited to receive once-weekly BTZ (1.3 mg/m2 body surface area) subcutaneously for 8 weeks followed by oral cyclophosphamide (1 mg/kg/d) for 4 months. The primary outcomes were the difference in antibody level at 8 and 48 weeks compared with baseline and the incidence of serious adverse events (AEs). The secondary outcome was the occurrence of opportunistic infections (OIs) during the 72 weeks after starting BTZ. The median patient age was 46 years (range, 34-53). All patients had 3-5 OIs prior to enrollment. All patients were receiving antimycobacterial agents for treatment of nontuberculous mycobacterial infection at enrollment. There was no significant difference in the mean optical density of auto-Abs at 8 weeks (3.73 ± 0.72) or 48 weeks (3.74 ± 0.53) compared with baseline (3.84 ± 0.49; P = .336 and P = .555, respectively). However, after serum dilution, the antibody titer nonsignificantly decreased 8-16 weeks after BTZ initiation (P = .345). Ten OIs were observed 24-72 weeks after BTZ initiation. Treatment with BTZ followed by cyclophosphamide yielded no significant decrease in antibody titer levels, and 10 OIs were observed during 24-72 weeks of BTZ treatment. No serious AEs were observed. Combining rituximab with BTZ is likely necessary to prevent generation of new autoantibody-producing plasma cells. Clinical Trials Registration. NCT03103555.

Epidemiology, Outcomes and Tolerability of Protracted Treatment of Nontuberculous Mycobacterial Infections at a Community Teaching Hospital in the Southeastern United States.

Nontuberculous mycobacterial (NTM) infections present a treatment challenge for clinicians and patients. There are limited data about current susceptibility patterns and treatment outcomes in U.S. adults. This was a 10-year, single-center, retrospective, observational cohort study of adults with a positive NTM culture and clinical suspicion of infection between 1 January 2010 and 30 June 2020. The primary objective was to identify predictors for favorable treatment outcomes. Key secondary objectives were characterization of NTM epidemiology, susceptibility profiles, and safety and tolerability of treatment, including the proportion of subjects with an antimicrobial change and the reasons for the change. Of 250 subjects diagnosed with NTM infection, the most prevalent NTM isolates were Mycobacterium avium intracellulare complex (66.8%) followed by Mycobacterium abscessus (17.6%). Antimicrobial susceptibility data were available for 52.4% of the cohort (45.8% slow growers; 54.2% rapid growers). Only 88 (35%) subjects received treatment with evaluable clinical outcomes. The proportion of subjects with a favorable outcome was 61.4%. More subjects in the unfavorable outcome group experienced a change in antimicrobial therapy (73.5% vs. 51.9%, p = 0.043). The most common reason for antimicrobial change was adverse drug events (n = 36, 67.9%). In the regression model, private insurance was associated with a favorable outcome, whereas having multiple antimicrobial changes was associated with an unfavorable outcome. The complexity of NTM treatment and high incidence of medication-related issues suggest the necessity of interdisciplinary collaboration to improve overall treatment outcomes in NTM infections.

Non-tuberculous mycobacterial infections in patients with end-stage renal disease: prevalence, risk factors, and mortality

Non-tuberculous mycobacterial (NTM) disease has increased in prevalence in the USA, however, little is known on NTM in the population with end-stage renal disease (ESRD). Thus, we investigated patients with...

Molecular identification of nontuberculous mycobacteria using the rpoB, argH and cya genes analysis

Nontuberculous mycobacterial (NTM) infections are growing worldwide especially in immunocompromised individuals. Since treatment of NTM infections is species-specific, the precise identification of NTM to species level is critical for an optimal treatment. This study was aimed to identify different NTM species by sequencing the rpoB gene and evaluating the effectiveness of argH and cya gene markers. In total 64 clinical isolates suspected to NTM were collected. The identification of the isolates was done by standard conventional methods and PCR-based rpoB gene and sequence analysis. PCR sequencing of argH and cya genes was performed to evaluate the efficacy of these genes in identifying and differentiating different species and subspecies of NTM. Among 64 isolates tested, 51 (79.68%) were detected by conventional tests as NTM. The results of rpoB sequence analysis revealed that the 56 clinical isolates were identified in 10 species of NTM and 8 remaining isolates which showed ambiguous results by rpoB sequencing, application of argH and cya sequencing could detect these isolates. Furthermore, by using cya gene sequencing, M. abscessus subspecies were properly differentiated. Although the rpoB sequencing as a standard method, is beneficial for detecting various species of NTM, however, based on our findings, argH and cya gene markers have a superb ability to discriminate closely related species. Further investigations are required to verify our outcomes.

Nano-in-Microparticles for Aerosol Delivery of Antibiotic-Loaded, Fucose-Derivatized, and Macrophage-Targeted Liposomes to Combat Mycobacterial Infections: In Vitro Deposition, Pulmonary Barrier Interactions, and Targeted Delivery.

Nontuberculous mycobacterial infections rapidly emerge and demand potent medications to cope with resistance. In this context, targeted loco-regional delivery of aerosol medicines to the lungs is an advantage. However, sufficient antibiotic delivery requires engineered aerosols for optimized deposition. Here, the effect of bedaquiline-encapsulating fucosylated versus nonfucosylated liposomes on cellular uptake and delivery is investigated. Notably, this comparison includes critical parameters for pulmonary delivery, i.e., aerosol deposition and the noncellular barriers of pulmonary surfactant (PS) and mucus. Targeting increases liposomal uptake into THP-1 cells as well as peripheral blood monocyte- and lung-tissue derived macrophages. Aerosol deposition in the presence of PS, however, masks the effect of active targeting. PS alters antibiotic release that depends on the drug's hydrophobicity, while mucus reduces the mobility of nontargeted more than fucosylated liposomes. Dry-powder microparticles of spray-dried bedaquiline-loaded liposomes display a high fine particle fraction of >70%,as well as preserved liposomal integrity and targeting function. The antibiotic effect is maintained when deposited as powder aerosol on cultured Mycobacterium abscessus. When treating M. abscessus infected THP-1 cells, the fucosylated variant enabled enhanced bacterial killing, thus opening up a clear perspective for the improved treatment of nontuberculous mycobacterial infections.

Clinical analysis of nontuberculous mycobacterial infection after minimally invasive plastic surgery and cosmetic surgery.

To investigate the clinical features, diagnosis, and treatment of nontuberculous mycobacterial infections after minimally invasive plastic surgery and cosmetic surgery, and to provide reference data for the management of affected patients. We retrospectively analyzed 12 cases of nontuberculous mycobacterial infection after minimally invasive plastic surgery and cosmetic surgery in our department from January 2014 to December 2020. The case data included baseline characteristics, morbidity, chronology of patient symptoms, diagnostic results, and treatment outcomes. Disease characteristics were summarized and objectively analyzed. The 12 patients infected with nontuberculous mycobacteria after plastic surgery and cosmetic surgery received small incision or minimally invasive surgery. The onset time was 5-30days after surgery, the clinical manifestations were non-specific, and ordinary antibiotics are ineffective. Small incisions or minimally invasive plastic surgery and cosmetic surgery have hidden dangers of nontuberculous mycobacterial infection, and the detection and diagnosis are difficult, and the treatment time is long, which requires attention.

Repurposing disulfiram to target infections caused by non-tuberculous mycobacteria.

Non-tuberculous mycobacteria are emerging pathogens of significant worldwide interest because they have inherent drug resistance to a wide variety of FDA-approved drugs and cause a broad range of serious infections. In order to identify new drugs active against non-tuberculous mycobacteria, we identified disulfiram, utilized for treatment of alcohol dependence, as exhibiting potent growth-inhibitory activity against non-tuberculous mycobacteria. Whole-cell growth inhibition assays were used to screen and identify novel inhibitors. The hit compounds were tested against Vero cells to determine the selectivity index, and this was followed by determining time-kill kinetics against Mycobacterium fortuitum and Mycobacterium abscessus. Disulfiram's ability to synergize with several approved drugs utilized for the treatment of M. fortuitum and M. abscessus was determined using fractional inhibitory concentration indexes followed by determining its ability to reduce mycobacterial infections ex vivo. Finally, disulfiram's in vivo potential was determined in a neutropenic murine model mimicking mycobacterial infection. We identified disulfiram as possessing potent antimicrobial activity against non-tuberculous mycobacteria. Disulfiram exhibited concentration- and time-dependent bactericidal activity against M. fortuitum as well as against M. abscessus and synergized with all drugs utilized for their treatment. Additionally, disulfiram reduced bacterial load in macrophages in an intracellular killing assay better than amikacin. When tested in a murine neutropenic M. fortuitum infection model, disulfiram caused significant reduction in bacterial load in kidneys. Disulfiram exhibits all properties required for it to be repositioned as a novel anti-mycobacterial therapy and possesses a potentially new mechanism of action. Thus, it can be considered as a potent structural lead for the treatment of non-tuberculous mycobacterial infections.

Biological evaluation of diphenyleneiodonium chloride (DPIC) as a potential drug candidate for treatment of non-tuberculous mycobacterial infections.

Novel drug discovery against non-tuberculous mycobacteria is beset with a large number of challenges including the existence of myriad innate drug resistance mechanisms as well as a lack of suitable animal models, which hinders effective translation. In order to identify molecules acting via novel mechanisms of action, we screened the Library of Pharmacologically Active Compounds against non-tuberculous mycobacteria to identify such compounds. Whole-cell growth inhibition assays were used to screen and identify novel inhibitors. The hit compounds were tested for cytotoxicity against Vero cells to determine the selectivity index, and time-kill kinetics were determined against Mycobacterium fortuitum. The compound's ability to synergize with amikacin, ceftriaxone, ceftazidime and meropenem was determined using fractional inhibitory concentration indexes followed by its ability to decimate mycobacterial infections ex vivo. Finally, the in vivo potential was determined in a neutropenic murine model mimicking mycobacterial infection. We have identified diphenyleneiodonium chloride (DPIC), an NADPH/NADH oxidase inhibitor, as possessing potent antimicrobial activity against non-tuberculous mycobacteria. DPIC exhibited concentration-dependent bactericidal activity against M. fortuitum and synergized with amikacin, ceftriaxone, ceftazidime and meropenem. When tested in a murine neutropenic M. fortuitum infection model, DPIC caused a significant reduction in bacterial load in kidney and spleen. The reduction in bacterial count is comparable to amikacin at a 100-fold lower concentration. DPIC exhibits all properties to be repositioned as a novel anti-mycobacterial therapy and possesses a potentially new mechanism of action. Thus, it can be projected as a potential new therapeutic against ever-increasing non-tuberculous mycobacterial infections.

Safety and Tolerability of Long Term Use of Tedizolid for Treatment of Nontuberculous Mycobacterial Infections

Safety and Tolerability of Long Term Use of Tedizolid for Treatment of Nontuberculous Mycobacterial Infections

Antimycobacterial, antioxidant and cytotoxic activities of essential oil of gall of <i>Pistacia atlantica</i> Desf. From Algeria

Background: The aim of this study was to assess the antimycobacterial, antioxidant and the cytotoxic activities of the essential oil from the gall part of Pistacia atlantica Desf from Algeria.Materials and Methods: The antimycobacterial activity was evaluated by the broth microdilution method against three species of mycobacteria: Mycobacterium smegmatis, Mycobacterium aurum and Mycobacterium fortuitum. Antioxidant activity was determined using free-radical scavenging assays. The safety of essential oil was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on C3A and Vero monkey kidney cells.Results: The minimal inhibitory concentration (MIC) values ranged from 0.16 to 2.5 mg/mL with minimal bactericidal concentration (MBC) values ranged from 0.62 to >2.5 mg/mL. The antioxidant activity showed IC50 values ranged between 417.61 - >2000μg/mL and 495.6 - >2000μg/mL for DPPH and ABTS assay respectively. The cytotoxicity assay showed LC50 ranged between 26.47 to 93.64 μg/mL against Vero cells and 74.29 to 225.40 μg/mL against C3A. The results of this study show that the essential oils from the gall of P. atlantica have low toxicity and moderate activity against fast growing M. smegmatis and M. aurum.Conclusion: These results substantiate their potential as used in the treatment of non-tuberculous mycobacterial infections. This finding is predictive of their activity against M. tuberculosis, therefore, further study might be considered to investigate the activity against pathogenic Mycobacterium strains.Key words: Pistacia atlantica, Essential oil, Antimycobacterial, Antioxidant, Cytotoxicity.

ANTIMYCOBACTERIAL, ANTIOXIDANT AND CYTOTOXIC ACTIVITIES OF ESSENTIAL OIL OF GALL OF PISTACIA ATLANTICA DESF. FROM ALGERIA

Background: The aim of this study was to assess the antimycobacterial, antioxidant and the cytotoxic activities of the essential oil from the gall part of Pistacia atlantica Desf from Algeria. 
 Materials and Methods: The antimycobacterial activity was evaluated by the broth microdilution method against three species of mycobacteria: Mycobacterium smegmatis, Mycobacterium aurum and Mycobacterium fortuitum. Antioxidant activity was determined using free-radical scavenging assays. The safety of essential oil was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on C3A and Vero monkey kidney cells. 
 Results: The minimal inhibitory concentration (MIC) values ranged from 0.16 to 2.5 mg/mL with minimal bactericidal concentration (MBC) values ranged from 0.62 to >2.5 mg/mL. The antioxidant activity showed IC50 values ranged between 417.61 - >2000µg/mL and 495.6 - >2000µg/mL for DPPH and ABTS assay respectively. The cytotoxicity assay showed LC50 ranged between 26.47 to 93.64 µg/mL against Vero cells and 74.29 to 225.40 µg/mL against C3A. The results of this study show that the essential oils from the gall of P. atlantica have low toxicity and moderate activity against fast growing M. smegmatis and M. aurum. 
 Conclusion: These results substantiate their potential as used in the treatment of non-tuberculous mycobacterial infections. This finding is predictive of their activity against M. tuberculosis, therefore, further study might be considered to investigate the activity against pathogenic Mycobacterium strains.

Cutaneous non‐tuberculous mycobacterial infections

Mycobacteria cause a range of diseases in both immunocompetent and immunosuppressed individuals and may affect many different organs. The most noticeable recent change in patterns of cutaneous mycobacterial infection refers to the increase in non-tuberculous mycobacterial (NTM) infections. This review focuses on the clinical manifestations, diagnosis, and treatment of cutaneous NTM infections. The MEDLINE, PubMed, and Cochrane Library databases were searched using the keywords "non-tuberculous mycobacteria," "atypical mycobacteria," and "mycobacteria other than tubercle bacilli". Publications on cutaneous NTM infections written in English were included in this review. Literature published by the World Health Organization was examined for further material. References in review articles were screened for other studies not already identified. The clinical features, diagnosis, and treatment of NTM infections were reviewed. Cutaneous mycobacterial disease may take many guises and may appear benign in nature. Chronic cutaneous lesions at the sites of trauma or surgical procedures, especially those that fail to respond to standard antibiotic therapy, should prompt the consideration of mycobacterial disease. The lack of rapid techniques for the identification of pathogens makes diagnosis challenging. The lack of randomized controlled trials on the efficacy of antimicrobial agents means that empiric therapy may fail, necessitate prolonged combinations of antibiotics, and increase the probability of side effects and diminished compliance.

Mycobacterium shigaense sp. nov., a novel slowly growing scotochromogenic mycobacterium that produced nodules in an erythroderma patient with severe cellular immunodeficiency and a history of Hodgkin’s disease

A novel slow-growing scotochromogenic mycobacterium was isolated from skin biopsies from a patient with a history of Hodgkin's disease and severe cellular immunodeficiency as an opportunistic pathogen. Clinical characterization of these lesions revealed papules and nodules with pathological granuloma formation. Genotypic analysis using 16S rRNA misidentified this isolate as Mycobacterium simiae. However, multiple gene analysis using the internal transcribed spacer between the 16S and 23S rRNA genes, and the rpoB and hsp65 genes revealed the presence of a novel mycobacterium. The antimicrobial susceptibility of this isolate was completely different from that of M.simiae. On the basis of these findings, we propose naming this new species Mycobacterium shigaense sp. nov., and conclude that multiple gene analysis is required for the appropriate diagnosis and treatment of non-tuberculous mycobacterial infections.

Nontuberculous mycobacterial disease in transplant recipients: early diagnosis and treatment

Infections due to nontuberculous mycobacterial (NTM) infections are increasing and, thus, it is likely that practitioners will see an increase in NTM infections in transplant recipients. There have been few recent comprehensive studies evaluating the epidemiology, diagnosis, and treatment of NTM infections in transplant recipients. Most recent studies have reported unusual and interesting manifestations of NTM infection. Other studies have described the posttransplant outcomes of patients with pretransplant cultures that grew NTM and provided recommendations regarding the appropriateness of performing transplants in these patients. Recent studies have documented the protean nature of the clinical presentation of NTM infections in transplant recipients. These studies, as well as previously published reports, highlight the need for a high index of suspicion for clinicians when managing transplant patients with unexplained fever, cutaneous lesions, joint infections, or radiographic opacities. Early diagnosis of NTM infection and initiation of therapy are needed to prevent morbidity and mortality in this vulnerable population.

Nontuberculous Mycobacterial Infections

Abstract Context.—Nontuberculous mycobacteria include numerous acid-fast bacilli species, many of which have only recently been recognized as pathogenic. The diagnosis of mycobacterial disease is based on a combination of clinical features, microbiologic data, radiographic findings, and histopathologic studies. Objective.—To provide an overview of the clinical and pathologic aspects of nontuberculous mycobacteria infection, including diagnostic laboratory methods, classification, epidemiology, clinical presentation, and treatment. Data Sources.—Review of the pertinent literature and published methodologies. Conclusions.—Nontuberculous mycobacteria include numerous acid-fast bacilli species, many of which are potentially pathogenic, and are classified according to the Runyon system based on growth rates and pigment production. Their slow growth hinders cultures, which require special medium and prolonged incubation. Although such methods are still used, newer nucleic acid–based technologies (polymerase chain reaction and hybridization assays) can rapidly detect and speciate some mycobacteria—most notably, distinguishing Mycobacterium tuberculosis from other species. Infections caused by these organisms can present as a variety of clinical syndromes, not only in immunocompromised patients but also in immunocompetent hosts. Most common among these are chronic pulmonary infections, superficial lymphadenitis, soft tissue and osteoarticular infections, and disseminated disease. Treatment of nontuberculous mycobacterial infections is difficult, requiring extended courses of multidrug therapy with or without adjunctive surgical intervention.

Report of oral clarithromycin desensitization

Antibiotic hypersensitivity can lead to significant morbidity, mortality and suboptimal treatment options. Rapid desensitization induces temporary immunological tolerance in a host with type 1 hypersensitivity reaction. We report a case of oral desensitization to clarithromycin. To our knowledge, this is the first protocol published for desensitization to macrolides. A 68-year-old female with a history of giant cell arteritis treated with oral corticosteroids and steroid-induced diabetes presented with small nodules and ulcers on the pre-tibial surface of her legs. Despite multiple courses of oral and parenteral antibiotics for cellulitis, the lesions continued to develop. Skin biopsy of the lesion demonstrated suppurative granuloma formation with acid-fast bacilli on microscopy. The patient reported anaphylaxis to erythromycin 20 years previously and bronchospasm to roxithromycin 5 years previously. She was commenced on rifampicin and moxifloxacin for mycobacterial skin infection, and Mycobacterium chelonaewas subsequently cultured. There was further clinical deterioration and her treatment was changed to doxycycline, intravenous amikacin and intravenous imipenem. Antibiotic susceptibility testing subsequently revealed the isolate was resistant to imipenem, so this was substituted with linezolid. Unfortunately, this was discontinued due to diarrhoea. Intravenous amikacin was not desired as a long-term treatment option due to risk of renal and ototoxicity. Clarithromycin is the treatment of choice for M. chelonae infection [1], but the patient had a strong history of type 1 hypersensitivity with macrolide antibiotics. No published protocol for rapid drug desensitization was available for clarithromycin, so a clarithromycin desensitization protocol was developed (Table 1). The protocol was administered in an intensive care unit with careful observation on a medical ward for 36 h afterwards. No adverse reaction was noted. Table 1 Oral clarithromycin desensitization protocol The patient continued doxycycline and clarithromycin for a total of 18 months. There was an excellent clinical response and no adverse drug reactions were recorded. Serious adverse drug reactions occur in 6.7% of hospitalized patients and rank from the fourth to sixth leading cause of death in these patients [2]. Since 1998 there has been a 2.6-fold increase in serious adverse drug reactions reported to the US Food and Drug Administration [3]. Type 1 (immediate) hypersensitivity reactions occur within minutes to hours of drug administration due to release of vasoactive substances from mast cells and basophils (often IgE-mediated). Clinical manifestations range from urticaria to life-threatening angio-oedema and anaphylaxis. Desensitization procedures were first developed in the 1960s [4]. Rapid desensitization involves incremental exposure to drug antigens at increasing concentrations leading to a therapeutic dose. Antigen-specific mast cell desensitization is thought to be the underlying mechanism for drug desensitization [5]. By inducing temporary clinical and immunological tolerance, patients are able to receive optimal treatment while avoiding or minimizing anaphylaxis and anaphylactoid reactions. Tolerance is maintained only if drug antigens are administered at regular intervals, and repeated desensitizations can also be given [6]. Desensitization protocols have been developed for a variety of drugs including penicillins, cephalosporins, vancomycin, sulfonamides, rifampicin, nonsteroidal anti-inflammatory drugs and chemotherapeutic agents (taxanes, platins). As specific skin prick testing to clarithromycin was not performed in our patient, we cannot be certain that an immediate hypersensitivity reaction would have occurred. However, given her previous immediate hypersensitivity reactions to other 14-membered macrolides erythromycin and roxithromycin, we felt that desensitization to clarithromycin was warranted. Skin prick testing has been well described for penicillins and cephalosporins, and is considered accurate for diagnosing penicillin allergy, as antigenic determinants have been well characterized [7]. Cross-sensitivity within the same antibiotic class is variable, however. There is little information available for diagnostic tests for macrolide allergy, as immediate hypersensitivity reactions are uncommon [8]. A patient in the literature with roxithromycin immediate hypersensitivity demonstrated positive skin prick testing to erythromycin and clarithromycin [9]. These macrolides have a similar chemical structure comprising a 14-membered carbon ring, compared with 15-membered macrolides (azithromycin) and 16-membered macrolides (spiramycin). Use of first-line antibiotics in certain conditions have been shown to have greater efficacy, for example trimethoprim + sulfamethoxazole for Pneumocystis jiroveci pneumonia [10, 11] or penicillin for syphilis, especially in HIV-infected individuals [12]. Macrolide antibiotics have an important role in the treatment of nontuberculous mycobacterial infections [13]. In our case report clarithromycin was a desirable treatment option, and rapid oral desensitization to clarithromycin was successful with no adverse events reported. We believe this is the first published protocol for desensitization to macrolide antibiotics and anticipate that its use can be extended to other centres worldwide.

Pneumonectomy for nontuberculous mycobacterial infections

Background Pneumonectomy is considered in the treatment of nontuberculous mycobacterial infections when an entire lung is affected. However, this procedure carries high morbidity. We report on our experience in using pneumonectomy for treating patients with nontuberculous mycobacterial infections. Methods Between 1983 and 2002, 53 patients infected with nontuberculous mycobacteria underwent 55 pulmonary resections. Of these patients, 11 (3 men, 8 women) underwent pneumonectomy (5 right, 6 left). Median age was 57 years (range, 43 to 69 years). Mycobacterium avium complex disease occurred in 10 patients and Mycobacterium abscessus disease in 1. Indications for pneumonectomy included multiple cavities in one lung and destruction of an entire lung. The bronchial stump was covered with a latissimus dorsi muscle flap in 7 patients and with an intercostal pedicle flap in 2. Results Operating time ranged from 142 to 477 minutes (median, 360 minutes). The median intraoperative blood loss was 555 mL (range, 130 to 1,245 mL). There was no operative mortality. Bronchopleural fistula occurred in 3 patients. All fistulas were observed after right pneumonectomy, and were treated by reclosure of the bronchus. Empyema occurred in 1 patient, who was treated with irrigation. All patients achieved sputum-negative status after surgery. Two late deaths occurred. One patient died of respiratory failure 11 months after surgery. A second patient, the only patient who had recurrent disease, died of respiratory failure 4 years postoperatively. Conclusions Despite bronchial stump protection, right pneumonectomy carries a risk for bronchopleural fistula. Nonetheless, pneumonectomy can result in high cure rates in patients with nontuberculous mycobacterial infections.

Mycobacterium phlei Infection of the Foot: A Case Report

A case of Mycobacterium phlei infection in the flexor digitorum longus and posterior tibialis tendon of an otherwise healthy adult male is reported. To our knowledge, this is the second reported case in the English literature of human infection by M. phlei. Diagnosis and treatment of nontuberculous mycobacterial infection are discussed. The clinician is encouraged to include this infection in the differential diagnosis of pain and swelling in the extremity.