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.

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.

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.

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.

Trimethoprim-sulfamethoxazole-induced lung injury: a case report.

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. While cutaneous adverse drug reactions associated with TMP-SMX are commonly recognized, lung toxicity induced by TMP-SMX is an unusual condition, with scattered reports of hypersensitivity pneumonitis, acute fibrinous organizing pneumonia, interstitial lung disease and acute respiratory distress syndrome. Reports of TMP-SMX-associated drug-induced lung injury (DLI) are rare in the pediatric population and its pathogenesis is not well understood. Diagnosis of DLI remains a challenge, given the wide range of clinical presentations that overlap with other conditions and the lack of diagnostic tests. In this report, we describe a case of TMP-SMX-induced lung injury in an eight-year-old child. Case Description: An eight-year-old girl presented in respiratory failure with acute symptoms of shortness of breath, fever, maculopapular rash and vomiting. This was associated with pneumonitis, pneumothorax, pneumomediastinum and subcutaneous emphysema on imaging. She had been on 25 days of TMP-SMX for treatment of Group D Salmonella bacteremia and osteomyelitis that was diagnosed prior to this current presentation. TMP-SMX was discontinued on admission due to concerns of possible drug reaction. Extensive infective, autoimmune and immunologic workup did not reveal the cause of the respiratory failure. Considering the absence of an alternative explanation for her clinical presentation and similarities in clinical courses to other reported cases, she was eventually diagnosed with TMP-SMX-associated DLI. She received a course of corticosteroids with subsequent clinical improvement and was weaned off home oxygen therapy a few months after her discharge from the hospital. Conclusions: Diagnosis of DLI can be challenging. The early identification of DLI and discontinuation of culprit drug is essential in its management. Further understanding of the underlying pathophysiology and risk factors for TMP-SMX-associated DLI is required.

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.

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.

Recurrent Urinary Tract Infection in Adult Patients, Risk Factors, and Efficacy of Low Dose Prophylactic Antibiotics Therapy.

BACKGROUND: Recurrent urinary tract infection (UTI) occurs in sizable percentages of patients after a single episode and is a frequent cause of primary healthcare visits and hospital admissions, accounting for up to one quarter of emergency department visits. We aim to describe the pattern of continuous antibiotic prophylaxis prescription for recurrent urinary tract infections, in what group of adult patients they are prescribed and their efficacy. METHODS: A retrospective chart review of all adult patients diagnosed with single and recurrent symptomatic urinary tract infection in the period of January 2016 to December 2018. RESULTS: A total of 250 patients with a single UTI episode and 227 patients with recurrent UTI episodes were included. Risk factors for recurrent UTI included diabetes mellitus, chronic renal disease, and use of immunosuppressive drugs, renal transplant, any form of urinary tract catheterization, immobilization and neurogenic bladder. E. coli infections were the most prevalent organism in patients with UTI episodes. Prophylactic antibiotics were given to 55% of patients with UTIs, Nitrofurantoin, Bactrim or amoxicillin clavulanic acid. Post renal transplant is the most frequent reason to prophylaxis antibiotics (44%). Bactrim was more prescribed in younger patients (P < 0.001), in post-renal transplantation (P < 0.001) and after urological procedures (P < 0.001), while Nitrofurantoin was more prescribed in immobilized patients (P = 0.002) and in patients with neurogenic bladder (P < 0.001). Patients who received continuous prophylactic antibiotics experienced significantly less episodes of urinary tract infections (P < 0.001), emergency room visits and hospital admissions due to urinary tract infections (P < 0.001). CONCLUSION: Despite being effective in reducing recurrent urinary tract infection rate, emergency room visits and hospital admissions due to UTI, continuous antibiotic prophylaxis was only used in 55% of patients with recurrent infections. Trimethoprim/sulfamethoxazole was the most frequently used prophylactic antibiotic. Urology and gynecological referral were infrequently requested as part of the evaluation process for patients with recurrent UTI. There was a lack of use of other interventions such as topical estrogen in postmenopausal women and documentation of education on non-pharmacological methods to decrease urinary tract infections.

How to diagnose and treat a patient without human immunodeficiency virus infection having Pneumocystis jirovecii pneumonia?

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in patients without HIV infection. In contrast to PCP in patients infected with HIV, diagnosis is often delayed and illness is associated with increased mortality. OBJECTIVES: To provide a comprehensive review of clinical presentation, risk factors, diagnostic strategies, and treatment options for PCP in patients without HIV infection. SOURCES: Web-based literature review on PCP for trials, meta-analyses, and systematic reviews using PubMed. The restriction to the English language was applied. CONTENT: Common underlying conditions in patients without HIV infection having PCP are haematological malignancies, autoimmune and inflammatory diseases, solid organ or haematopoietic stem cell transplant, and previous corticosteroid exposure. New risk groups include patients receiving monoclonal antibodies and immunomodulating therapies. Patients without HIV infection who have PCP present with rapid onset and progression of pneumonia, increased duration of hospitalization and a significantly higher mortality rate than patients infected with HIV. PCP is diagnosed by a combination of clinical symptoms and radiological as well as mycological features. Results of immunofluorescence microscopy from bronchoalveolar lavage, PCR testing, and computed tomography imaging as well as the evaluation of clinical presentation are required. The established treatment regime consists of trimethoprim and sulfamethoxazole. IMPLICATIONS: Although the number of patients with immunosuppression due to causes different from HIV is increasing, a simultaneous rise in PCP incidence is observed. In the group of patients without HIV infection, rapid onset of symptoms, a more complex course, and a high mortality rate are recorded. Therefore, the time to diagnosis must be as short as possible to initiate effective therapy promptly. This review aims to raise awareness of PCP in an increasingly affected at-risk group and provides clinicians with a practical guide for efficient diagnosis and targeted therapy. Furthermore, it intends to display current inadequacies in research on the topic of PCP.

Rapid detection of pulmonary nocardiosis by metagenomic next generation sequencing.

We retrospectively analyzed 3 cases of pulmonary nocardiosis. Patients were identified by metagenomic next generation sequencing (mNGS) in the First Affiliated Hospital of Soochow University, from January 2019 to April 2022. All patients had underlying diseases, and were in immunocompromised state, with membranous nephropathy, acute lymphoblastic leukemia (ALL), and systemic lupus erythematosus (SLE), respectively. Symptoms common to all cases included fever, cough and expectoration. Chest computed tomography (CT) presented patchy shadows or nodules, with or without cavitation lesions, or pleural effusion. mNGS detected Nocardia spp. via bronchoalveolar lavage fluid (BALF) or blood samples from patients. All the patients were discharged with recovery after using the trimethoprim-sulfamethoxazole (TMP-SMX) and remained without evidence of disease during regular follow-ups. mNGS may be a tool for rapid and accurate detection and identification of pulmonary nocardiosis, but interpreting the mNGS results should be more cautious because the mNGS assay can also detect colonization.

Trimethoprim/sulfamethoxazole desensitization in an HIV-positive patient with previous Stevens-Johnson syndrome; a failed study.

Drug-induced Stevens-Johnson syndrome (SJS) is a rare but life-threatening hypersensitivity reaction. Drug desensitization might be considered in drug-allergic patients with no therapeutic alternative. A 29-year-old man with a recent diagnosis of HIV and HBV (CD4 count: 4 cells/mm3) who has been receiving Trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis pneumonia (PCP) prophylaxis was admitted at Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, with the diagnosis of SJS due to TMP/SMX. After 45 days of supportive care, the patient was a candidate for TMP/SMX desensitization due to our region's unavailability of alternative agents. A 9-day desensitization protocol was used, but the patient complained about diarrhea with severe pain in the rectal mucosa, and macules developed over his lips again on the third day. As a result, the desensitization process immediately stopped, and after the signs and symptoms were resolved, the patient was discharged with Clindamycin tablet 600 mg TDS. Unfortunately, two weeks after discharge, the patient experienced acute kidney injury (AKI) and expired after two dialysis sessions.

Global prevalence and distribution of antibiotic resistance among clinical isolates of Stenotrophomonas maltophilia: A systematic review and meta-analysis.

OBJECTIVES: Stenotrophomonas maltophilia (S. maltophilia), an opportunistic pathogen, causes infection in patients undergoing immunosuppressive therapy, mechanical ventilation, or catheters and in long-term hospitalized patients. Due to its extensive resistance to various antibiotics and chemotherapeutic agents, S. maltophilia is challenging to treat. Using case reports, case series, and prevalence studies, the current study provides a systematic review and meta-analysis of antibiotic resistance profiles across clinical isolates of S. maltophilia. METHODS: A systematic literature search was performed for original research articles published in Medline, Web of Science, and Embase databases from 2000 to 2022. Statistical analysis was performed using STATA 14 software to report antibiotic resistance of S. maltophilia clinical isolates worldwide. RESULTS: 223 studies (39 case reports/case series and 184 prevalence studies) were collected for analysis. A meta-analysis of prevalence studies demonstrated that the most antibiotic resistance worldwide was to levofloxacin, trimethoprim-sulfamethoxazole (TMP/SMX), and minocycline (14.4%, 9.2%, and 1.4%, respectively). Resistance to TMP/SMX (36.84%), levofloxacin (19.29%), and minocycline (1.75%) were the most prevalent antibiotic resistance types found in evaluated case reports/case series studies. The highest resistance rate to TMP/SMX was reported in Asia (19.29%), Europe (10.52%), and America (7.01%), respectively. CONCLUSION: Considering the high resistance to TMP/SMX, more attention should be paid to patients' drug regimens to prevent the emergence of multidrug-resistant S. maltophilia isolates.

Nocardia arthritidis scleritis: A case report.

Purpose: This report describes a case and management of a 69-year-old female with infectious scleritis found to be caused by Nocardia arthritidis species. Observations: Our patient presented with severe constant pain in the left eye (OS) following cataract surgery. She had a pertinent past medical history significant for renal transplantation (on oral tacrolimus, mycophenolate, and prednisone). Slit lamp examination OS (1 month after cataract surgery) demonstrated 3+ injection temporally accompanied by scleral thickening and multiloculated abscesses with purulent drainage from small conjunctival erosions. The abscesses were debrided and sent for gram stain and culture. The patient was treated with repeated subconjunctival injections of antibiotics and an antifungal; topical amphotericin, vancomycin, and amikacin; and oral trimethoprim-sulfamethoxazole (double strength). Two separate gram stains with cultures confirmed the diagnosis and species identification. The patient responded well to repeat subconjunctival injections early on in addition to the prescribed regimen, remaining free of disease at the last follow-up (12 months following presentation). Conclusions and Importance: This unique case demonstrates infectious scleritis caused by an uncommon Nocardia species (N. arthritidis) that was successfully treated with similar strategies used for other reported Nocardia species. As Nocardia scleritis can lead to adverse outcomes if not treated promptly and properly, it should be considered on the differential diagnoses in an immunocompromised patient who presents with acute ocular symptoms after any recent ocular surgery.

Trimethoprim-Sulfamethoxazole-Induced Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Complicated by Acute Liver Failure.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a delayed adverse drug reaction that is characterized by fever, cutaneous manifestation, enlarged lymph nodes, hematologic abnormalities, and organ involvement. Multiple medications have been reported to cause DRESS with the presentation varying from drug to drug. Some cases are mild and can be managed by stopping the causative agent along with supportive measures; however, other cases can lead to multi-organ failure requiring systemic corticosteroids and organ transplant. Acute liver failure is a rare manifestation of DRESS. We report a patient who had recently completed a course of trimethoprim-sulfamethoxazole and presented with low-grade fever, diffuse skin rash, eosinophilia, elevated liver enzymes, acute kidney injury, and thrombocytopenia. DRESS was subsequently diagnosed based on history, physical examination, and relatively negative workup for an alternate diagnosis. The patient eventually showed improvement with steroid therapy without the need for a liver transplant. Due to its pharmacogenetic susceptibility, it is essential to recommend avoiding the causative medication for the patient's family members.

Cotrimoxazole-induced hyperkalemia in renal transplant patient-Case report.

We present the case of a 55-year-old male patient who developed hyperkalemia after using Cotrimoxazole (TMP-SMX). There was a marked increase in potassium levels from 3.3 mEq/L on Day 5 when cotrimoxazole was started to 6.2 mEq/L on Day 11 when the drug was withheld.

Case report: Nocardia farcinica pneumonia in early-stage post liver transplantation.

Background: Liver transplantation is a well-established treatment for end-stage liver disease. The evolution of immunosuppressants has supported the recent advances in this field. However, this leads to immunosuppression and increases the risk for infections. Nocardia is an aerobic gram-positive bacillus, which can cause multi-systemic or multi-organ infections. Nocardia is an opportunistic pathogen that principally affects immunosuppressed patients. Case presentation: Herein, we present a case of Nocardia farcinica pneumonia in a patient at early-stage post-liver transplantation. Following appropriate microbiological tests and imaging, the diagnosis was finally confirmed. A full recovery was achieved after optimal antibiotic therapy of sulfamethoxazole, minocycline, and amikacin. Conclusions: Nocardia farcinica pneumonia is a rare and life-threatening disease, especially in patients after liver transplantation. Imaging and microbiological tests are helpful for the early diagnosis of the disease. Trimethoprim-sulfamethoxazole (TMP-SMX) as part of first-line therapy for nocardiosis is recommended.

Stenotrophomonas Maltophilia and Urinary Tract Infections: A Systematic Review.

Stenotrophomonas maltophilia, a gram-negative bacillus well known to cause respiratory tract infections, is increasingly being reported to cause urinary tract infections (UTI). In our review of the literature comprising six articles, males were more prone to developing UTIs, with the mean age of the patients being 62.5 ±18.9 years. While several risk factors have been associated with the development of the disease, patients with underlying urological or nephrological diseases tend to develop a more severe illness. The organism was sensitive to trimethoprim-sulfamethoxazole (TMP-SMX) in the majority of cases. This systematic review also aims to shed light on the possible mechanisms of resistance adopted by the bacteria, modes of transmission, and strategies to prevent the transmission and development of the disease.