A fatal case of disseminated nocardiosis due to Nocardia otitidiscaviarum resistant to trimethoprim-sulfamethoxazole: case report and literature review.

BACKGROUND: Disseminated nocardiosis still causes significant morbidity and mortality and is often caused by Nocardia asteroides, N. basiliensis, and N. farcinica and are often treated with trimethoprim-sulfamethoxazole (TMP-SMX). Nocardia otitidiscaviarum (N. otitidiscaviarum) rarely causes disseminated disease and resistance to TMP-SMX is even more rare. CASE PRESENTATION: A 37-year-old woman with metastatic breast cancer and right ear deafness with recent occupational gardening and manipulating soil, presented to the hospital with first time seizure and multiple skin nodules. Magnetic resonance imaging (MRI) showed ring enhancing lesions, biopsy of the skin and brain lesions grew N. otitidiscaviarum. She was empirically treated with TMP-SMX and Imipenem-Cilastatin, however, almost three weeks into therapy, susceptibility results revealed it to be resistant to both antimicrobials, she was subsequently changed to Amikacin, Linezolid, Moxifloxacin, and Doxycycline but ultimately died. CONCLUSIONS: This case report highlights the importance of suspecting a rare Nocardia species in patients at risk with proper occupational exposure, moreover, TMP-SMX resistance should be suspected with lack of clinical response, this may have important implications on clinical practice when facing similar infections.

Prophylactic antibiotic treatment with TMP-SMX decreased the incidence of interstitial pneumonia in patients with B-cell lymphoma on chemotherapy.

BACKGROUND: Several studies have reported the incidence of interstitial pneumonia (IP) among patients with non-Hodgkin lymphoma (NHL) that are undergoing combination chemotherapy plus rituximab; however, the effective prophylactic treatment for IP remains unclear. This study aims to explore the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) on IP and identify IP-associated risk factors in NHL patients. METHODS: Between March 2013 and April 2018, 498 patients (264 males, 53%) with B-cell NHL undergoing first-line RCHOP-like chemotherapy treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone were enrolled in this study. RESULTS: These patients had a median age of 56 years, and 311 of the 498 patients (62.4%) were administered once daily with the prophylactic treatment of TMP-SMX. IP occurred in 65 patients (13.1%), indicating a significant reduction in the IP incidence rate (21.4% vs. 8.0%; p < 0.001). Among patients treated with TMP-SMX, 2 (1.2%) exhibited rashes, 38 (12.2%) suffered from nausea and vomiting, 52 (16.7%) showed signs of neutropenia, and 18 (5.8%) suffered from kidney dysfunction. Both univariate and multivariate analysis showed that gender (male), history of diabetes, and absence of prophylactic TMP-SMX treatment were significant risk factors associated with IP. Disease progression was observed in 55/311 (17.7%) patients that underwent prophylactic TMP-SMX treatment and in 63/187 (33.7%) patients that did not (p < 0.001). CONCLUSIONS: This study revealed that the occurrence of IP was common in B-cell NHL patients undergoing combined chemotherapy plus rituximab treatment. IP could be reduced with prophylactic treatment of once-daily oral TMP-SMX.

Nocardia amikacinitolerans and cytomegalovirus: distinctive clinical and radiological characterization of the rare etiologies of brain abscesses: report of 2 cases.

Central nervous system infections in immunosuppressed patients are rare but potentially lethal complications that require swift diagnoses and intervention. While the differential diagnosis for new lesions on neuroradiological imaging of immunosuppressed patients typically includes infections and neoplasms, image-based heuristics to differentiate the two has been shown to have variable reliability.The authors describe 2 rare CNS infections in immunocompromised patients with atypical physical and radiological presentations. In the first case, a 59-year-old man, who had recently undergone a renal transplantation, was found to have multifocal Nocardia amikacinitolerans abscesses masquerading as neoplasms on diffusion-weighted imaging (DWI); in the second case, a 33-year-old man with suspected recurrent Hodgkin's lymphoma was found to have a nonpyogenic abscess with cytomegalovirus (CMV) encephalitis.As per review of the literature, this appears to be the first case of brain abscess caused by N. amikacinitolerans, a recently isolated superbug. Despite confirmation through brain biopsy later on in case 1, the initial radiological appearance was atypical, showing subtle diffusion restriction on DWI. Similarly, the authors present a case of CMV encephalitis that presented as a ring-enhancing lesion, which is extremely rare. Both cases draw attention to the reliability of neuroimaging in differentiating an abscess from a neoplasm.

[Pneumocystis pneumonia prophylaxis with low-dose trimethoprim/sulfamethoxazole during rituximab-containing chemotherapy].

Although Pneumocystis pneumonia (PCP), a life-threatening infection, has been reported in patients with non-Hodgkin B-cell lymphoma (BNHL) who were treated with rituximab-containing chemotherapies (R-CTX), the PCP prophylaxis regimen awaits establishment to date. This study reports a retrospective analysis of the efficacy and safety of a low-dose trimethoprim/sulfamethoxazole (TMP/SMX) in patients with BNHL receiving R-CTX. We retrospectively analyzed 156 patients newly diagnosed with BNHL who received R-CTX at our institute from 2010 to 2015. We collected patients' clinical and laboratory data, including lymphocytes count, IgG level, PCP prophylaxis regimens, and adverse events (AEs). Patients were categorized into the following two groups based on the TMP/SMX regimen: group A (33 patients; 80 mg/400 mg×3/week) or group B (65 patients; 160 mg/800 mg×2/week). Both lymphocytes count and IgG level declined during R-CTX. No patient developed PCP. Patients in group B exhibited a significantly higher incidence of AEs (18.2% vs. 63.1%; p<0.05) and increased AST (6.1% vs. 26.6%; p<0.05), compared with those in group A. Thus, TMP/SMX (80 mg/400 mg×3/week) effectively prevents PCP and is preferable because of the lower rates of AEs.

A 20-year experience with nocardiosis in solid organ transplant (SOT) recipients in the Southwestern United States: A single-center study.

BACKGROUND: Nocardiosis is a life-threatening opportunistic infection. Solid organ transplant (SOT) recipients are at higher risk (incidence 0.04%-3.5%) of developing nocardiosis. Rate of nocardiosis in the Southwestern US may be high due to environmental factors. METHODS: We performed a retrospective review study on 54 SOT patients diagnosed with Nocardia between 1997 and 2016 at our center. To explore the association of various risk factors with both the development of disseminated disease and mortality, a series of Fisher's exact tests was used. FINDINGS: Incidence of nocardiosis in SOT patients was 2.65%. Fisher's exact tests revealed no association between development of disseminated disease and the following variables: transplant rejection (P = 1), elevated tacrolimus levels (P = .4), and CMV viremia (P = .06). Also, we did not find any association between mortality and the variables we evaluated: type of transplant, transplant rejection, renal failure, disseminated nocardia, and patient's age. Overall mortality and 1-year mortality were 17% and 11%. INTERPRETATION: Based on our findings, daily 1 DS TMP/SMX prophylaxis did not appear to provide reliable protection against nocardiosis. However, we could not state definitely that TMP/SMX prophylaxis was or wasn't protective because of lack control group. None of the Fisher's exact tests revealed associations between the tested risk factors and either disease dissemination or mortality. This could be due to a true lack of association between the variables in each pair. However, it is also likely that our relatively small sample size limited our power to detect underlying relationships that may be present. Compared with other studies, 1-year mortality was lower at our institution (11% vs 16%).

A case of drug-induced lupus erythematosus secondary to trimethoprim/sulfamethoxazole presenting with pleural effusions and pericardial tamponade.

We report a case of drug-induced lupus erythematosus (DILE) secondary to trimethoprim/sulfamethoxazole (TMP/SMX) in a patient with underlying inflammatory bowel disease (IBD). The initial presentation was with febrile pleural and pericardial effusions followed by cardiac tamponade. The patient was treated with a short course of corticosteroids with complete resolution of symptoms. To our knowledge this is the first reported case of TMP/SMX-induced DILE presenting with life-threatening serositis. When confronted with sterile exudative effusions, clinicians should strongly consider non-infectious etiologies.

The role of CD4 cell count as discriminatory measure to guide chemoprophylaxis against Pneumocystis jirovecii pneumonia in human immunodeficiency virus-negative immunocompromised patients: A systematic review.

BACKGROUND: In recent years, the incidence of Pneumocystis jirovecii pneumonia (PJP) has increased in immunocompromised patients without human immunodeficiency virus (HIV) infection. Chemoprophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is highly effective in preventing PJP in both HIV-positive and -seronegative patients. In HIV-positive patients, the risk of PJP is strongly correlated with decreased CD4 cell count. The role of CD4 cell count in the pathogenesis of PJP in non-HIV immunocompromised patients is less well studied. For most immunosuppressive conditions, no clear guidelines indicate whether to start TMP-SMX. METHOD: We conducted a systematic literature review with the aim to provide a comprehensive overview on the role of CD4 cell counts in managing the risk of PJP in HIV-seronegative patients. RESULTS: Of the 63 individual studies retrieved, 14 studies report on CD4 cell counts in a variety of immunosuppressive conditions. CD4 cell count were <200/µL in 73.1% of the patients. CONCLUSION: CD4 cell count <200/µL is a sensitive biomarker to identify non-HIV immunocompromised patients who are at risk for PJP. Measuring CD4 cell counts could help clinicians identify patients who may benefit from TMP-SMX prophylaxis.

Itraconazole vs. trimethoprim-sulfamethoxazole: A comparative cohort study of 200 patients with paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America. Brazil accounts for approximately 80% of cases, where it represents a major public health issue due to its disabling impact and the number of premature deaths it causes. We present a retrospective cohort study that was conducted in order to better understand factors that relate to cure of the infection in the treatment of 200 patients with PCM. We evaluated the influence of sociodemographic and clinical factors as well as therapeutic regimen (trimethoprim-sulfamethoxazole [TMP-SMX] and itraconazole) on the progress of PCM (cure and noncure). There was a higher incidence of cure (83%) among patients who regularly received treatment for their infections and completed the treatment protocol. Moreover, itraconazole (86.4%) was significantly superior to TMP-SMX (51.3%) in terms of cure rate and had a median treatment period that was significantly shorter (12 months) than that for TMP-SMX (23 months). A Cox proportional hazard regression model showed that use of itraconazole increased the hazard of cure, regardless of sex, age, education, clinical form, completion of treatment, and regularity. Although the results of this study show that itraconazole was the best treatment option for PCM patients, a double-blind, randomized, controlled trial is necessary to confirm this conclusion.

Susceptibility of clinical Moraxella catarrhalis isolates in British Columbia to six empirically prescribed antibiotic agents.

BACKGROUND: Moraxella catarrhalis is a commensal organism of the respiratory tract that has emerged as an important pathogen for a variety of upper and lower respiratory tract infections including otitis media and acute exacerbations of chronic bronchitis. Susceptibility testing of M catarrhalis is not routinely performed in most diagnostic laboratories; rather, a comment predicting susceptibility based on the literature is attached to the report. The most recent Canadian report on M catarrhalis antimicrobial susceptibility was published in 2003; therefore, a new study at this time was of interest and importance. OBJECTIVE: To determine the susceptibility of M catarrhalis isolates from British Columbia to amoxicillin-clavulanate, doxycycline, clarithromycin, cefuroxime, levofloxacin and trimethoprimsulfamethoxazole. METHODS: A total of 117 clinical M catarrhalis isolates were isolated and tested from five Interior hospitals and two private laboratory centres in British Columbia between January and December 2012. Antibiotic susceptibility of M catarrhalis isolates was characterized using the Etest (E-strip; bioMérieux, USA) according to Clinical Laboratory Standards Institute guidelines. RESULTS: All isolates were sensitive to amoxicillin-clavulanate, doxycycline, clarithromycin, levofloxacin and trimethoprimsulfamethoxazole. One isolate was intermediately resistant to cefuroxime, representing a 99.15% sensitivity rate to the cephem agent. Cefuroxime minimum inhibitory concentrations (MICs) inhibiting 50% and 90% of organisms (MIC50 and MIC90) were highest among the antibiotics tested, and the MIC90 (3 µg/mL) of cefuroxime reached the Clinical Laboratory Standards Institute breakpoint of susceptibility. DISCUSSION: The antibiotic susceptibility of M catarrhalis isolates evaluated in the present study largely confirms the findings of previous surveillance studies performed in Canada. Cefuroxime MICs are in the high end of the sensitive range and the MIC50 and MIC90 observed in the present study are the highest ever reported in Canada. CONCLUSION: Although cefuroxime MICs in M catarrhalis are high, all agents tested showed antimicrobial activity, supporting their continued therapeutic and empirical use.

HISTORIQUE: Le Moraxella catarrhalis est un organisme commensal des voies respiratoires, qui se révèle un pathogène important dans diverses infections des voies respiratoires supérieures et inférieures, y compris l'otite moyenne et les exacerbations aiguës de la bronchite chronique. Dans la plupart des laboratoires diagnostiques, les tests de susceptibilité au M catarrhalis ne sont pas effectués systématiquement. Un commentaire en prédisant la susceptibilité d'après les publications est joint au rapport. Le dernier rapport canadien sur la susceptibilité du M catarrhalis aux antimicrobiens a été publié en 2003. Il est donc judicieux et important de publier une nouvelle étude à ce sujet. OBJECTIF: Déterminer la susceptibilité des isolats de M catarrhalis provenant de la Colombie-Britannique à l'amoxicilline-clavulanate, à la doxycycline, à la clarithromycine, à la céfuroxime, à la lévofloxacine et au triméthoprime-sulfaméthoxazole. MÉTHODOLOGIE: Au total, 117 isolats cliniques de M catarrhalis provenant de cinq hôpitaux de l'intérieur et de deux laboratoires privés de la Colombie-Britannique ont été prélevés et examinés entre janvier et décembre 2012. Les chercheurs ont caractérisé la susceptibilité aux antibiotiques des isolats de M catarrhalis au moyen de l'Etest (E-strip; bioMérieux, États-Unis), conformément aux lignes directrices du Clinical Laboratory Standards Institute. RÉSULTATS: Tous les isolats étaient sensibles à l'amoxicillineclavulanate, à la doxycycline, à la clarithromycine, à la lévofloxacine et au triméthoprime-sulfaméthoxazole. Un isolat était moyennement résistant à la céfuroxime, représentant un taux de sensibilité de 99,15 % à l'agent céphème. Les concentrations minimales inhibitrices (CMI) de la céfuroxime inhibant 50 % et 90 % des organismes (CMI50 et CMI90) étaient les plus élevées des antibiotiques à l'étude, et la CMI90 (3 µg/mL) de la céfuroxime atteignait le seuil de susceptibilité du Clinical Laboratory Standards Institute. EXPOSÉ: La susceptibilité des isolats de M catarrhalis aux antibiotiques évalués dans la présente étude confirme largement les observations tirées d'études de surveillance antérieures effectuées au Canada. Les CMI de la céfuroxime se situent dans la plage supérieure de sensibilité. De plus, la CMI50 et la CMI90 observées dans la présente étude sont les plus élevées jamais déclarées au Canada. CONCLUSION: Même si les CMI de la céfuroxime dans les isolats de M catarrhalis sont élevées, tous les agents étudiés présentaient une activité antimicrobienne, ce qui appuie la poursuite de leur utilisation dans un cadre thérapeutique et empirique.

HIV treatments have malaria gametocyte killing and transmission blocking activity.

BACKGROUND: Millions of individuals being treated for human immunodeficiency virus (HIV) live in malaria-endemic areas, but the effects of these treatments on malaria transmission are unknown. While drugs like HIV protease inhibitors (PIs) and trimethoprim-sulfamethoxazole (TMP-SMX) have known activity against parasites during liver or asexual blood stages, their effects on transmission stages require further study. METHODS: The HIV PIs lopinavir and saquinavir, the nonnucleoside reverse-transcriptase inhibitor nevirapine, and the antibiotic TMP-SMX were assessed for activity against Plasmodium falciparum transmission stages. The alamarBlue assay was used to determine the effects of drugs on gametocyte viability, and exflagellation was assessed to determine the effects of drugs on gametocyte maturation. The effects of drug on transmission were assessed by calculating the mosquito oocyst count as a marker for infectivity, using standard membrane feeding assays. RESULTS: Lopinavir and saquinavir have gametocytocidal and transmission blocking activities at or approaching clinically relevant treatment levels, while nevirapine does not. TMP-SMX is not gametocytocidal, but at prophylactic levels it blocks transmission. CONCLUSIONS: Specific HIV treatments have gametocyte killing and transmission-blocking effects. Clinical studies are warranted to evaluate these findings and their potential impact on eradication efforts.

Pneumocystis jirovecii pneumonia in non-HIV patients: need for a more extended prophylaxis.

Background: Pneumocystis jirovecii pneumonia (PCP) has a significant mortality rate for non-HIV immunocompromised patients. Prevention is primarily based on combined trimethoprim and sulfamethoxazole (TMP-SMX) but guidelines on pneumocystosis prophylaxis are scattered and not consensual. Objectives: This study aims to describe PCP in non-HIV patients and to review case by case the prior indication of prophylaxis according to specific guidelines.We included patients with confirmed diagnosis of PCP admitted to one university hospital from 2007 to 2020. Prior indication for pneumocystis prophylaxis was assessed according to the specific guidelines for the underlying pathology or treatment. Results: Of 150 patients with a medical diagnosis of PCP, 78 were included. Four groups of underlying pathologies were identified: hematological pathologies (42%), autoimmune diseases (27%), organ transplantation (17%), and other pathologies at risk of PCP (14%). A small subgroup of 14 patients (18%) had received a prior prescription of pneumocystis prophylaxis but none at the time of the episode. Transfer to intensive care was necessary for 33 (42%) patients, and the mortality rate at 3 months was 20%. According to international disease society guidelines, 52 patients (59%) should have been on prophylaxis at the time of the pneumocystis episode. Lowest compliance with guidelines was observed in the hematological disease group for 24 patients (72%) without prescription of indicated prophylaxis. Conclusion: Infectious disease specialists should draw up specific prophylactic guidelines against pneumocystis to promote a better prevention of the disease and include additional criteria in their recommendations according to individual characteristics to prevent fatal cases.

Disseminated nocardiosis caused by Nocardia otitidiscaviarum-A case report.

In this article we report a case of disseminated nocardiosis caused by Nocardia otitidiscaviarum in an immunocompetent patient with chronic obstructive pulmonary disease (COPD) who complained of a cough, followed by skin and intracranial lesions. On metagenomic next-generation sequencing (mNGS) technology of respiratory samples (bronchoalveolar lavage fluid, BALF) Nocardia otitidiscaviarum was identified. The patient was treated with therapy combined with a low dose of TMP-SMX and imipenem cilastatin sodium and had a favorable outcome. The timely diagnosis of Nocardia with the help of mNGS technology and early rational treatment of TMP-SMX can help improve the prognosis.

A Rare Case Report of Disseminated Nocardia Farcinica Granulomatous Hepatitis and Clinical Management Experience.

Background: Nocardiosis is primarily an opportunistic infection affecting immunocompromised individuals, with a predilection for the lungs, brain, or skin in those with compromised immune function. Granulomatous hepatitis caused by Nocardia is a rare clinical manifestation. This study aims to provide a systematic overview of the clinical features of Nocardiosis caused by Nocardia farcinica, enhancing our understanding of this disease. Methods: We report a case of a 75-year-old male with no underlying diseases presenting with a history of "recurrent fever for more than 4 months", along with fatigue, poor appetite, and pleural and abdominal effusion. Despite treatment at multiple hospitals, the patient showed little improvement. Chest CT revealed chronic inflammation, small nodules, bilateral pleural effusion, and pleural thickening. Abdominal CT indicated multiple low-density lesions in the liver, multiple small calcifications, and abdominal effusion. Results: Liver biopsy suggested inflammatory changes, with focal granuloma formation. Metagenomic next-generation sequencing (mNGS) of liver tissue indicated Nocardia farcinica, leading to the final diagnosis of disseminated Nocardia farcinica granulomatous hepatitis. Conclusion: Nocardia infection is a rare disease primarily observed in immunocompromised patients but can also occur in those with normal immune function. The clinical and radiological features lack specificity; however, the utilization of mNGS technology enables rapid identification of the pathogenic microorganism. Nocardia farcinica is generally susceptible to sulfonamide drugs and amikacin, offering viable treatment options.

Thirty-day risk of digoxin toxicity among older adults co-prescribed trimethoprim-sulfamethoxazole versus amoxicillin: A population-based cohort study.

IMPORTANCE: Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity. OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin. DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688). EXPOSURE: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin. MAIN OUTCOME AND MEASURE: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD. RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]). CONCLUSION AND RELEVANCE: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.

Prediction for Risk of Hypouricemia in Hospitalized Patients: A Single-center, Retrospective Cohort Study.

Background Hypouricemia, defined as a serum uric acid (SUA) level ≤2 mg/dL, could be a risk factor for death in hospitalized patients. However, how explanatory variables can explain hypouricemia as an objective variable in a logistic regression analysis remains unknown. Purpose To predict the risk factors for hypouricemia in hospitalized patients using a robust Bayesian logistic (RBL) model. Methods This study retrospectively enrolled patients who visited Yonago Medical Center between April 2020 and March 2021. The association between potential risk factors and hypouricemia was analyzed using the RBL model in Python-modulated PyMC3. The final model was selected based on the lowest Watanabe-Akaike information criterion (WAIC). Results Of the 618 patients, 64 (10.4%) had hypouricemia. Based on the model according to the lowest WAIC, independent risk factors for hypouricemia were febuxostat [odds ratio (OR) 5.46, 95% confidence interval (CI) 2.32-13.4], amino acids in parenteral nutrition (OR 5.19, 95% CI 1.62-15.1), TMP-SMX (OR 4.20, 95% CI 1.66-10.9), emaciation (OR 3.48, 95% CI 1.75-7.21), and serum sodium level (OR 0.90, 95% CI 0.84-0.96). Conclusion The RBL model predicted amino acids in parenteral nutrition, TMP-SMX, emaciation, and low serum sodium levels for hypouricemia, in addition to the authentic risk factor febuxostat.

Pneumocystis Pneumonia in Locally Advanced Breast Cancer Despite Prophylactic Use of Trimethoprim-Sulfamethoxazole During Prednisolone Treatment for a Pembrolizumab-Induced Immune-Related Adverse Event: A Case Report.

Pneumocystis pneumonia (PCP) primarily affects immunosuppressed patients, with trimethoprim-sulfamethoxazole (TMP-SMX) commonly used for prophylaxis. However, there is insufficient information on PCP occurrence despite TMP-SMX prophylaxis. We encountered a 57-year-old woman with locally advanced breast cancer developing PCP despite prophylactic intake of TMP-SMX, during treatment with prednisolone for Stevens-Johnson syndrome (SJS) induced by pembrolizumab. This case underscores the need to pay attention to the possibility of PCP development even during TMP-SMX prophylaxis. Dosage and duration adjustments according to the patient's condition and weight may be required.

Genitourinary skin and soft tissue infections: a prospective contemporary evaluation of causative pathogens.

PURPOSE: Prior literature identified anaerobes as the predominant causative organisms in genitourinary skin and soft tissue infections. However, the increasing prevalence of community acquired, methicillin resistant Staphylococcus aureus infection has brought about the growing need to reevaluate these infections and their causative organisms. We examined the causative organisms and risk factors in suppurative superficial genitourinary infections, and evaluated the growing role of community acquired, methicillin resistant S. aureus. MATERIALS AND METHODS: We performed a single institution, prospective assessment of 60 adults who presented between August 2008 and July 2010 with genitourinary skin and soft tissue infections requiring incision and drainage. Patients completed a standardized, nonvalidated questionnaire before undergoing débridement of the site. RESULTS: A total of 60 patient specimens were obtained and 92 bacterial pathogens were isolated. Of these pathogens 55% were aerobes. S. aureus was the most predominant cultured organism, representing 25% of all cultured organisms, and 65% of these isolates were community acquired, methicillin resistant S. aureus. The most commonly associated comorbidities included diabetes mellitus, tobacco smoking and heavy alcohol use. HIV/AIDS showed a statistically significant association with community acquired, methicillin resistant S. aureus infection (OR 11.00, 95% CI 1.05-115.51, p = 0.0456), as did the cumulative number of community acquired, methicillin resistant S. aureus risk factors (OR 2.64, 95% CI 1.31-5.33, p = 0.007). CONCLUSIONS: Aerobic organisms now account for most of these infections and community acquired, methicillin resistant S. aureus has emerged as a significant causative organism. Populations that may be at increased risk for these infections include patients with diabetes mellitus, heavy alcohol users and tobacco smokers. In patients with HIV/AIDS or multiple community acquired, methicillin resistant S. aureus risk factors the latter organism is more likely to be the causative organism.

Anti-tumor activity of trimethoprim-sulfamethoxazole against melanoma skin cancer through triggering allergic reaction and promoting immunity.

The anti-cancer impact of an allergic reaction is strongly linked to immunity enhancement. Trimethoprim-sulfamethoxazole (TMP-SMX), an antibiotic, has potential immunomodulatory effects, but has side effects such as allergies. Thus far, the effects and underlying mechanisms of TMP-SMX in melanoma have not been clarified. This study examined the potential roles of TMP-SMX in melanoma skin cancer using an immunodeficient mouse model. TMP-SMX significantly improved the survival rate and reduced the tumor weight and growth and vascular endothelial growth factor levels in melanoma skin cancer of immunodeficient mice. In the forced swimming test, TMP-SMX significantly reduced immobility time compared to the melanoma skin cancer of immunodeficient mice, indicating improved immunity. TMP-SMX significantly increased infiltration of mast cells and release of allergy-related mediators (IgE, histamine, interleukin (IL)-4, IL-5, IL-13, and IL-33) and immune-enhancing mediators (tumor necrosis factor-α, IL-2, IL-6, and IL-12). In addition, the administration of TMP-SMX significantly increased the caspase-3, 8, and 9 activities. Furthermore, mice given TMP-SMX showed no adverse reactions according to the blood biochemical parameters. TMP-SMX significantly inhibits the growth of melanoma skin cancer by triggering an allergic reaction and promotingimmunity. Hence, we propose that TMP-SMX may be used as an immune booster in cancer chemotherapy.

TMP-SMX induced type 4 hypersensitivity with multi-organ involvement.

Trimethoprim-sulfamethoxazole (TMP-SMX), also referred to as co-trimazole, is a common antibiotic used to treat a wide range of infections ranging from simple skin and soft tissue infections to opportunistic infections such as Pneumocystis jirovecii. Generally, this medication is well-tolerated, but severe adverse reactions, such as myelosuppression and hepatitis, can occur, albeit rarely. In this case report, we describe a patient who presented to the hospital with symptoms of rash, elevated liver enzymes, thrombocytopenia, and acute kidney injury 2 weeks after completing a course of TMP-SMX for a skin infection. We highlight the difficulties in diagnosing adverse events associated with this drug due to the variability in its presentation and the unpredictable onset of symptoms. By excluding common differential diagnoses including thrombotic thrombocytopenic purpura (TTP) and glucose-6-phosphate- dehydrogenase (G6PD) deficiency, we concluded that the patient was suffering from TMP-SMX-induced multi-organ dysfunction and treated him supportively. Through this case report, we aim to elucidate the importance of early recognition and treatment of the adverse effects of TMP-SMX.