Monkeypox virus cytologic findings: An institutional experience with an emerging threat.

OBJECTIVES: Mpox is a viral disease caused by monkeypox, a highly contagious orthopoxvirus that resulted in a global outbreak beginning in spring 2022. Diagnosis is confirmed via polymerase chain reaction (PCR) testing of swabs from mucocutaneous lesions. Rare reports have documented the histologic changes of mpox lesions, but the cytologic features have not been described. We present the cytology findings of samples taken from swabs of mucocutaneous mpox lesions in 3 different patients. METHODS: The patients were all male, aged 55, 43, and 37 years, all with mpox confirmed by PCR testing. Swabs from chest (cases 1 and 2) and tongue (case 3) lesions were directly sampled and submitted in Aptima (case 1) or PreservCyt solution (cases 2 and 3). Liquid-based preps were prepared and stained using the Papanicolaou method. Specimens were assessed for viral cytopathic changes. RESULTS: All cases showed nuclear cytopathic changes (enlarged nuclei with open chromatin and prominent red nucleoli), 2 cases demonstrated multinucleated keratinocytes, and 1 case showed potential Guarnieri bodies. The chromatin margination and nuclear molding typical of herpesviruses was not appreciated. CONCLUSIONS: The cytopathic changes of monkeypox are not specific, but their recognition could prompt appropriate PCR testing. Monkeypox shows distinct cytologic changes compared with herpesviruses.

Mechanisms by which the cystic fibrosis transmembrane conductance regulator may influence SARS-CoV-2 infection and COVID-19 disease severity.

Patients with cystic fibrosis (CF) exhibit pronounced respiratory damage and were initially considered among those at highest risk for serious harm from SARS-CoV-2 infection. Numerous clinical studies have subsequently reported that individuals with CF in North America and Europe-while susceptible to severe COVID-19-are often spared from the highest levels of virus-associated mortality. To understand features that might influence COVID-19 among patients with cystic fibrosis, we studied relationships between SARS-CoV-2 and the gene responsible for CF (i.e., the cystic fibrosis transmembrane conductance regulator, CFTR). In contrast to previous reports, we found no association between CFTR carrier status (mutation heterozygosity) and more severe COVID-19 clinical outcomes. We did observe an unexpected trend toward higher mortality among control individuals compared with silent carriers of the common F508del CFTR variant-a finding that will require further study. We next performed experiments to test the influence of homozygous CFTR deficiency on viral propagation and showed that SARS-CoV-2 production in primary airway cells was not altered by the absence of functional CFTR using two independent protocols. On the contrary, experiments performed in vitro strongly indicated that virus proliferation depended on features of the mucosal fluid layer known to be disrupted by absent CFTR in patients with CF, including both low pH and increased viscosity. These results point to the acidic, viscous, and mucus-obstructed airways in patients with cystic fibrosis as unfavorable for the establishment of coronaviral infection. Our findings provide new and important information concerning relationships between the CF clinical phenotype and severity of COVID-19.

The host-directed therapeutic imatinib mesylate accelerates immune responses to Mycobacterium marinum infection and limits pathology associated with granulomas.

Infections caused by members of the mycobacterium tuberculosis complex [MTC] and nontuberculous mycobacteria [NTM] can induce widespread morbidity and mortality in people. Mycobacterial infections cause both a delayed immune response, which limits rate of bacterial clearance, and formation of granulomas, which contain bacterial spread, but also contribute to lung damage, fibrosis, and morbidity. Granulomas also limit access of antibiotics to bacteria, which may facilitate development of resistance. Bacteria resistant to some or all antibiotics cause significant morbidity and mortality, and newly developed antibiotics readily engender resistance, highlighting the need for new therapeutic approaches. Imatinib mesylate, a cancer drug used to treat chronic myelogenous leukemia [CML] that targets Abl and related tyrosine kinases, is a possible host-directed therapeutic [HDT] for mycobacterial infections, including those causing TB. Here, we use the murine Mycobacterium marinum [Mm] infection model, which induces granulomatous tail lesions. Based on histological measurements, imatinib reduces both lesion size and inflammation of surrounding tissue. Transcriptomic analysis of tail lesions indicates that imatinib induces gene signatures indicative of immune activation and regulation at early time points post infection that resemble those seen at later ones, suggesting that imatinib accelerates but does not substantially alter anti-mycobacterial immune responses. Imatinib likewise induces signatures associated with cell death and promotes survival of bone marrow-derived macrophages [BMDMs] in culture following infection with Mm. Notably, the capacity of imatinib to limit formation and growth of granulomas in vivo and to promote survival of BMDMs in vitro depends upon caspase 8, a key regulator of cell survival and death. These data provide evidence for the utility of imatinib as an HDT for mycobacterial infections in accelerating and regulating immune responses, and limiting pathology associated with granulomas, which may mitigate post-treatment morbidity.

Sinonasal Amoebiasis: An Unexpected Cause of Sinonasal Necroinflammatory Disease.

While amoebic infection is widely known as a cause of gastroenteritis, keratitis, and meningoencephalitis, amoebae are challenging to recognize at unexpected sites. Despite multiple case reports of sinonasal amoebiasis, amoebic infection is not regularly considered in the differential diagnosis of sinonasal necroinflammatory disease. Here, we aim to characterize the pathologic features of sinonasal amoebiasis to facilitate better recognition. We identified sinonasal amoebiasis in 4 men, median age of 67 years (range: 37 to 71 y). All were immunocompromised, including 2 with chronic lymphocytic leukemia, 1 with human immunodeficiency virus, and 1 with human immunodeficiency virus and kidney transplant. Patients presented with nasal mucosal necrosis or polypoid masses, with facial ulceration in 1 patient and distant dermal nodules in another. Biopsies displayed extensive necrotic debris and inflammation. Although amoebic cysts were abundant in 3 cases, they were mistaken for yeast at frozen section in 1 case; 1 case showed only rare trophozoites that were not recognized on initial biopsy. Periodic acid Schiff and Grocott Methenamine Silver stains highlighted the organisms, and polymerase chain reaction confirmed Acanthamoeba species in 3 cases tested. 2 patients responded well to antiprotozoal medications, but 2 died of disease. Overall, sinonasal amoebiasis presents as a necroinflammatory process in patients immunocompromised for various reasons. Amoebae can mimic other organisms or be incredibly scarce, requiring active consideration to recognize amoebiasis and differentiate it from overlapping conditions like invasive fungal sinusitis, granulomatosis with polyangiitis, and natural killer/T-cell lymphoma. Because sinonasal amoebiasis is highly treatable when diagnosed promptly, pathologists play a critical role in the recognition of this rare necroinflammatory disease.

Haemophagocytic lymphohistiocytosis associated with bartonella peliosis hepatis following kidney transplantation in a patient with HIV.

Bacillary peliosis hepatis is a well recognised manifestation of disseminated Bartonella henselae infection that can occur in immunocompromised individuals. Haemophagocytic lymphohistiocytosis is an immune-mediated condition with features that can overlap with a severe primary infection such as disseminated Bartonella spp infection. We report a case of bacillary peliosis hepatis and secondary haemophagocytic lymphohistiocytosis due to disseminated Bartonella spp infection in a kidney-transplant recipient with well controlled HIV. The patient reported 2 weeks of fever and abdominal pain and was found to have hepatomegaly. He recalled exposure to a sick dog but reported no cat exposures. Laboratory evaluation was notable for pancytopenia and cholestatic injury. The patient met more than five of eight clinical criteria for haemophagocytic lymphohistiocytosis. Pathology review of a bone marrow core biopsy identified haemophagocytosis. A transjugular liver biopsy was done, and histopathology review identified peliosis hepatis. Warthin-Starry staining of the bone marrow showed pleiomorphic coccobacillary organisms. The B henselae IgG titre was 1:512, and Bartonella-specific DNA targets were detected by peripheral blood PCR. Treatment with doxycycline, increased prednisone, and pausing the mycophenolate component of his transplant immunosuppression regimen resulted in an excellent clinical response. Secondary haemophagocytic lymphohistiocytosis can be difficult to distinguish from severe systemic infection. A high index of suspicion can support the diagnosis of systemic Bartonella spp infection in those who present with haemophagocytic lymphohistiocytosis, especially in patients with hepatomegaly, immunosuppression, and germane animal exposures.

Infections Caused by Free-Living Amoebae.

Infections caused by Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris result in a variety of clinical manifestations in humans. These amoebae are found in water and soil worldwide. Acanthamoeba spp. and B. mandrillaris cause granulomatous amoebic encephalitis (GAE), which usually presents as a mass, while N. fowleri causes primary amoebic meningoencephalitis (PAM). Acanthamoeba spp. can also cause keratitis, and both Acanthamoeba spp. and B. mandrillaris can cause lesions in skin and respiratory mucosa. These amoebae can be difficult to diagnose clinically as these infections are rare and, if not suspected, can be misdiagnosed with other more common diseases. Microscopy continues to be the key first step in diagnosis, but the amoeba can be confused with macrophages or other infectious agents if an expert in infectious disease pathology or clinical microbiology is not consulted. Although molecular methods can be helpful in establishing the diagnosis, these are only available in referral centers. Treatment requires combination of antibiotics and antifungals and, even with prompt diagnosis and treatment, the mortality for neurological disease is extremely high.

Strengthening Pathology Capacity to Deliver Quality Cancer Care in Cities in LMICs.

Diagnostic pathology services for oncology health systems are essential; yet, surveys, observations, and hard data from across low- and middle-income countries have revealed that these services are almost always lacking adequate quality and often missing completely. The City Cancer Challenge Foundation (C/Can), the American Society for Clinical Pathology, and C/Can partner cities undertook intense analysis of their existing pathology services as part of a year-long assessment process including the specific formation of a pathology-focused team. Internal and external expert assessments identified sustainable solutions adapted to the local context and level of resources and created specific local implementation projects. Through local leadership, capacity development, and collaboration, services were improved city-wide in three cities: Cali, Colombia; Asunción, Paraguay; and Yangon, Myanmar. Common problems identified across cities included deficiencies in personnel training, equipment, reagents, processes, quality, and coordination. Specific solutions included quality training, standard process development and regulation, implementation of new services, and public-private collaboration. As the first cities joining the C/Can initiative, Cali, Asunción, and Yangon demonstrate the success of the approach and the value of local expertise in identifying problems and solutions. The additional value of international partners' expertise created opportunities for growth through mentorship and technical support. Importantly, the power of healthcare programs with strong political support is emphasized.

Adenovirus causing hepatic abscess formation and unexplained fever in adult liver transplant recipients.

Adenovirus infection is commonly associated with self-limited respiratory and gastrointestinal illnesses. However, infection in immunocompromised individuals, such as transplant recipients, can cause severe life-threatening illness including pneumonitis, hemorrhagic cystitis, nephritis, hepatitis, and enterocolitis. In orthotopic liver transplant recipients, adenovirus viremia can cause hepatitis leading to marked transaminitis, allograft loss, and death. Although hepatic abscesses mediated by adenovirus have been described in other immunosuppressed patient populations, it has very rarely been described in liver transplant recipients. Here, we report two adult cases of hepatic abscesses following liver transplantation secondary to adenovirus infection and describe the successful treatment of these patients. Adenovirus should be considered as an uncommon etiology of hepatic abscess and unexplained fevers in adults following liver transplantation.

La pandemia de Coronavirus SARS-CoV-2 (COVID-19): Situación actual e implicaciones para México / The SARS-CoV-2 (COVID-19) coronavirus pandemic: current situation and implications for Mexico

Resumen La pandemia del Coronavirus (COVID-19) es una de las más devastadoras de este siglo. Originada en China en diciembre de 2019 y causada por el virus SARS-CoV-2, en menos de 1 mes ya había sido catalogada como "Emergencia de Salud Pública de Alcance Internacional". A la fecha hay cerca de 3 millones de personas con infección confirmada y ha provocado más de 250,000 fallecimientos en el mundo. Inicialmente afecta las vías respiratorias con neumonías atípica y en casos graves provoca inflamación sistémica con liberación de citoquinas que pueden provocar un rápido deterioro, insuficiencia circulatoria, respiratoria y alteraciones de coagulación con una letalidad cercana al 7%. En México, el primer caso se detectó en febrero del 2020, y a la fecha de esta publicación se cuenta con 29,616 casos confirmados y 2,961 fallecimientos en toda la extensión de país. La baja tasa de muestreo diagnóstico en nuestro país claramente subestima la incidencia e impacto de esta enfermedad. Los grupos mas afectados son aquéllos con factores de riesgo como lo son la edad mayor a 60 años, hipertensión, diabetes o historia de enfermedad cardiovascular. De los casos confirmados, 15% son trabajadores del sector salud. No existe hasta ahora un tratamiento específico o vacuna, de tal manera que es importante contar con las medidas de higiene, aislamiento social y protección personal. Las consecuencias en salud, sociales y económicas podrían ser de gran impacto en los tiempos por venir.

Abstract The Coronavirus pandemic (COVID-19) is one of the most devastating in this century. It originated in China in December 2019 caused by the SARS-Cov-2 virus, and in less than a month it had been classified as an "International Public Health Emergency". To date there are nearly 3 million people infected and more than 250,000 deaths caused by the disease worldwide. Initially it affects the respiratory tract with atypical pneumonia and in severe cases it produces systemic inflammation with cytokine storm that can cause rapid deterioration with circulatory and respiratory failure, coagulopathy and a lethality rate of approximately 7%. In Mexico, the first case was detected in February 2020, and to date there are 26,616 confirmed cases and 2,961 deaths throughout the country. The low number of diagnostic tests conducted in our country clearly underestimates the real incidence and impact of the disease. The most affected groups are those with risk factors such as age over 60, presence of hypertension, diabetes or cardiovascular disease. Of the confirmed cases, 15% are healthcare workers. There is no specific treatment or vaccine yet, so it is important to have hygiene, social isolation and personal protection measures. Health, social and economic consequences could have great impact in the near future.

Emerging and reemerging fungal infections.

Fungal infections throughout the world appear to be increasing. This may in part be due to the increase in the population of patients that are susceptible to otherwise rare fungal infections resulting from the use of immune modulating procedures such as hematopoietic stem cell transplants and drugs like tissue necrosis factor antagonists. Histoplasma capsulatum, an endemic fungus throughout North and South America, is reemerging among HIV+ patients in Central and South America and among patients taking tissue necrosis factor antagonists and other biologics in North America. Fusarium species, a relatively rare fungal infection, is reemerging worldwide in the immunocompromised populations, especially those who are neutropenic like hematopoietic stem cell transplant recipients. A new yeast species is currently emerging worldwide: Candida auris, unknown just a decade ago. It is causing large healthcare-associated outbreaks on four continents and is spreading throughout the world through patient travel. In this review the epidemiology, pathology, detection and treatment of these three emerging and reemerging fungi will be discussed.

Circulating inflammation-related markers and advanced gastric premalignant lesions.

BACKGROUND AND AIM: Chronic Helicobacter pylori infection causes gastric mucosal inflammation as an important antecedent of gastric cancer. We aimed to evaluate associations of blood markers of inflammation with gastric intestinal metaplasia and dysplasia in H. pylori-infected individuals. METHODS: We compared pre-treatment serum levels of immune-related and inflammation-related markers between 99 individuals with intestinal metaplasia or dysplasia and 75 control individuals with non-atrophic gastritis within an H. pylori eradication trial in Mexico. Serum levels of 28 markers measured with Luminex bead-based assays were categorized in tertiles as low (T1), middle (T2), and high (T3). Logistic regression models were used to calculate age-adjusted and sex-adjusted odds ratios and 95% confidence intervals. All statistical tests were two-sided, and significance values were adjusted for multiple comparisons using false discovery rate methods. RESULTS: Five markers were nominally associated (Ptrend  < 0.05) with the presence of advanced premalignant gastric lesions. Adjusted odds ratios (95% confidence interval) of T2 and T3 versus T1 were 4.09 (1.65-10.17) and 3.08 (1.23-7.68) for CCL3/MIP1A, 3.21 (1.33-7.75) and 2.69 (1.10-6.57) for CCL20/MIP3A levels, 1.79 (0.77-4.18) and 2.39 (1.02-5.60) for IL-1ß, 1.34 (0.56-3.19) and 3.02 (1.29-7.12) for IL-4, and 1.07 (0.44-2.59) and 3.07 (1.32-7.14) for IL-5, respectively. Two (IL-4 and IL-5) of the five markers had false discovery rate adjusted Ptrend  < 0.2. CONCLUSIONS: Our results suggest that certain Th2 and other cytokines may have a role in promoting carcinogenesis in the setting of H. pylori infection. Additional research is needed to replicate these findings, extend to pre-diagnostic samples, and elucidate the underlying mechanisms.

Improving Anatomic Pathology in Sub-Saharan Africa to Support Cancer Care.

OBJECTIVES: Cancer care requires both accurate pathologic diagnosis as well as pathologic cancer staging. We evaluated three approaches to training pathologists in sub-Saharan Africa to perform pathologic cancer staging of breast, cervix, prostate, and colorectal cancers. METHODS: One of three training methods was used at each workshop: didactic, case-based testing (CBT), or a blended approach. The project involved 52 participants from 16 pathology departments in 11 countries in East, Central, and Southern Africa. Evaluation of each method included pre- and postworkshop knowledge assessments, online pre- and postworkshop surveys of practice changes at the individual and institutional levels, and selected site visits. RESULTS: While CBT resulted in the highest overall average postassessment individual scores, both CBT and blended approaches resulted in 19% increases in average scores from pre- to postworkshop assessments. Institutions that participated in the blended workshop had increased changes in practice as indicated by the institutional survey. CONCLUSIONS: Both CBT and a blended approach are effective methods for training pathologists in pathologic cancer staging. Both are superior to traditional lectures alone.

Creation and pilot testing of cases for case-based learning: A pedagogical approach for pathology cancer diagnosis.

BACKGROUND: Case-based learning (CBL) is an established pedagogical active learning method used in various disciplines and defined based on the field of study and type of case. The utility of CBL for teaching specific aspects of cancer diagnosis to practising pathologists has not been previously studied in sub-Saharan Africa. OBJECTIVES: We aimed to pilot test standardised cancer cases on a group of practising pathologists in sub-Saharan Africa to evaluate case content, clarity of questions and delivery of content. METHODS: Expert faculty created cases for the four most commonly diagnosed cancers. The format included mini-cases and bullet cases which were all open-ended. The questions dealt with interpretation of clinical information, gross specimen examination, morphologic characteristics of tumours, ancillary testing, reporting and appropriate communication to clinicians. RESULTS: Cases on breast, cervical, prostate and colorectal cancers were tested on seven practising pathologists. Each case took an average of 45-90 min to complete.Questions that were particularly challenging to testers were on: Specimens they should have been but for some reason were not exposed to in routine practice.Ancillary testing and appropriate tumour staging.New knowledge gained included tumour grading and assessment of radial margins. Revisions to cases were made based on testers' feedback, which included rewording of questions to reduce ambiguity and adding of tables to clarify concepts. CONCLUSION: Cases were created for CBL in Kenya, but these are applicable elsewhere in Africa and beyond to teach cancer diagnosis. The pilot testing of cases prepared faculty for the actual CBL course and feedback provided by the testers assisted in improving the questions and impact on day-to-day practice.

Cryptococcal antigen negative meningoencephalitis in HIV/AIDS.

Diagnosis of central nervous system cryptococcosis relies on a spectrum of methods but has improved with lateral flow diagnostic assays that detect capsular polysaccharide antigens of Cryptococcus. Here, we present the case of an HIV-infected African-American man with cryptococcal meningoencephalitis caused by a strain producing little or no capsule.

A novel presentation of Mycobacterium avium complex in a recipient of a lung transplant: a case report.

BACKGROUND: Lung transplantation remains an important potential therapeutic option for end-stage lung disease. It can improve quality of life and in some cases be a life-lengthening therapy. Despite the possible benefits, there are also many potential complications following transplantation. Here we describe a novel presentation of nontuberculous mycobacterium manifesting as an endobronchial mass developing 4 years after lung transplantation. CASE PRESENTATION: A 66-year-old African-American woman presented with progressive dyspnea, cough, and persistent wheezing of 2 months' duration. She had a distant history of breast cancer and received bilateral lung transplantation due to end-stage pulmonary fibrosis 4 years prior to her current presentation. She denied fevers, but did endorse night sweats. She had diffuse expiratory wheezing on auscultation. Chest computed tomography imaging showed an endobronchial soft tissue lesion nearly occluding the left mainstem bronchus, which was concerning for endobronchial carcinoma. Rigid bronchoscopy demonstrated a fibrinous mass protruding into the left mainstem proximal to the anastomosis. A pathology report noted fragments of partially necrotic granulation tissue in addition to scant fragments of focally ulcerated bronchial mucosa. Both the tissue culture and bronchial wash stained positively for acid-fast bacilli and grew Mycobacterium avium complex. CONCLUSIONS: Nontuberculous mycobacterium pulmonary disease is common post lung transplant and risk factors are related to immunosuppression and history of structural lung disease. Mycobacterium avium complex presenting as an endobronchial lesion in a patient post lung transplant is a novel presentation.

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis.

Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 µg/ml. The median lung tissue free pyrazinamide concentration was 20.96 µg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = -0.66, P = 0.04) and acid-fast bacilli (R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens.

Disseminated Acanthamoeba Infection Presenting With Cutaneous Lesions in an Immunocompromised Patient: A Case Report, Review of Histomorphologic Findings, and Potential Diagnostic Pitfalls.

OBJECTIVES: Free-living amoebas are exceedingly rare causes of cutaneous infections and present unique diagnostic and therapeutic challenges. We describe a case of disseminated acanthamoebiasis with cutaneous manifestations and summarize additional diagnostic, prognostic, and therapeutic highlights. METHODS: A 58-year-old man with relapsed chronic lymphocytic leukemia had several weeks of progressive, painful ulcerations on the forehead, arms, abdomen, and thighs. A biopsy was performed for histopathologic evaluation. RESULTS: The biopsy specimen showed inflammatory infiltrate with abscess formation involving the epidermis, dermis, and subcutis. Scattered cells showed nuclei with a prominent central karyosome, dispersed chromatin, and either abundant foamy basophilic cytoplasm or two well-demarcated cytoplasmic walls. Acanthamoeba species was confirmed by polymerase chain reaction from the formalin-fixed, paraffin-embedded tissue. CONCLUSIONS: Cutaneous lesions from acanthamoebiasis are exceptionally rare but should be included in the differential diagnosis of necrotic cutaneous lesions in immunocompromised patients. Although infrequently encountered, pathologists need to be aware of the morphologic features of free-living amoebas. Immunohistochemical and molecular studies can confirm the diagnosis. Multiagent treatment regimens, when initiated empirically, have been more successful than single-agent regimens, but infections involving the central nervous system are almost universally fatal.

Cavitary penetration of levofloxacin among patients with multidrug-resistant tuberculosis.

A better understanding of second-line drug (SLD) pharmacokinetics, including cavitary penetration, may help optimize SLD dosing. Patients with pulmonary multidrug-resistant tuberculosis (MDR-TB) undergoing adjunctive surgery were enrolled in Tbilisi, Georgia. Serum was obtained at 0, 1, 4, and 8 h and at the time of cavitary removal to measure levofloxacin concentrations. After surgery, microdialysis was performed using the ex vivo cavity, and levofloxacin concentrations in the collected dialysate fluid were measured. Noncompartmental analysis was performed, and a cavitary-to-serum levofloxacin concentration ratio was calculated. Twelve patients received levofloxacin for a median of 373 days before surgery (median dose, 11.8 mg/kg). The median levofloxacin concentration in serum (Cmax) was 6.5 µg/ml, and it was <2 µg/ml in 3 (25%) patients. Among 11 patients with complete data, the median cavitary concentration of levofloxacin was 4.36 µg/ml (range, 0.46 to 8.82). The median cavitary/serum levofloxacin ratio was 1.33 (range, 0.63 to 2.36), and 7 patients (64%) had a ratio of >1. There was a significant correlation between serum and cavitary concentrations (r = 0.71; P = 0.01). Levofloxacin had excellent penetration into chronic cavitary TB lesions, and there was a good correlation between serum and cavitary concentrations. Optimizing serum concentrations will help ensure optimal cavitary concentrations of levofloxacin, which may enhance treatment outcomes.

Fatal aortic pseudoaneurysm from disseminated Mycobacterium kansasii infection: case report.

Mycobacterium kansasii is a photochromogenic, slow-growing mycobacterium species that can cause pulmonary infection in patients with predisposing lung diseases, as well as extrapulmonary or disseminated disease in immunosuppressed patients. We describe a patient with a myelodysplastic syndrome, disseminated M kansasii infection, and ruptured aortic aneurysm. He had a recent diagnosis of mycobacterium cavitary lung lesions and was transferred to our facility for possible surgical intervention of an aortic aneurysm. Few hours after admission, the patient suddenly collapsed and died despite resuscitation efforts. A complete autopsy was performed and showed ruptured ascending aortic pseudoaneurysm with hemopericardium, disseminated necrotizing and nonnecrotizing granulomas with acid-fast bacilli in the aortic wall, lungs, heart, liver, spleen, and kidneys. Further genetic studies were consistent with monocytopenia and mycobacterial infection syndrome.