A retrospective study of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in adult patients with hematologic malignancies-its utility during respiratory virus pandemics.

OBJECTIVES: In hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected categories of intensive chemotherapy for hematologic malignancies. Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent; however, its use is not straightforward. Inhaled pentamidine is the recommended second-line agent; however, aerosolized medications were discouraged during respiratory virus outbreaks, especially during the COVID-19 pandemic, in view of potential contamination risks. Intravenous (IV) pentamidine is a potential alternative agent. We evaluated the effectiveness and tolerability of IV pentamidine use for PCP prophylaxis in adult allogeneic hematopoietic stem cell transplantation recipients and patients with hematologic malignancies during COVID-19. RESULTS: A total of 202 unique patients who received 239 courses of IV pentamidine, with a median of three doses received (1-29). The largest group of the patients (49.5%) who received IV pentamidine were undergoing or had received a hematopoietic stem cell transplant. The most common reason for not using TMP-SMX prophylaxis was cytopenia (34.7%). We have no patients who had breakthrough PCP infection while on IV pentamidine. None of the patients developed an infusion reaction or experienced adverse effects from IV pentamidine. CONCLUSIONS: Pentamidine administered IV monthly is safe and effective.

Evaluation of effectiveness, hyperkalaemia, and hepatotoxicity of trimethoprim-sulphamethoxazole prophylaxis for Pneumocystis jirovecii pneumonia in paediatric patients: A single-centre retrospective study.

BACKGROUND: American guidelines recommend trimethoprim-sulphamethoxazole (TMP-SMX) for preventing Pneumocystis jirovecii pneumonia (PJP) in paediatric patients at doses of 5-10 mg/kg/d of the TMP component, administered either daily, three times weekly, or twice weekly. However, limited studies describe the effectiveness and safety of these prophylactic regimens. Our study aimed to assess the clinical effectiveness and incidence of adverse events associated with each TMP-SMX regimen in paediatric patients, and to identify risk factors for adverse events. METHODS: We collected data regarding the onset of PJP, hyperkalaemia, and hepatotoxicity in patients aged 0-18 years who underwent prophylaxis with TMP-SMX from July 2018 to June 2023. RESULTS: A total of 215 paediatric patients met the inclusion criteria. No patients developed PJP. Hyperkalaemia occurred in 14.7%, patients receiving TMP-SMX daily, 15.4% receiving it three times weekly, and 15.5% receiving it twice weekly. Hepatotoxicity was most frequent in patients receiving TMP-SMX twice weekly (19%), followed by those receiving it three times weekly (7.7%), and daily (5.9%). Younger patients were significantly more prone to developing hyperkalaemia or hepatotoxicity. Patients aged <1 year had the highest incidences of hyperkalaemia (56.5%), and those aged 1-2 years had the highest incidence of hepatotoxicity (25%). CONCLUSIONS: No patient developed PJP under various dosage prophylactic regimens of TMP-SMX. However, our findings suggest the need to monitor potassium levels and hepatic function in patients undergoing any of the three TMP-SMX regimens. In particular, patients aged <1 year old and 1-2 years old face a higher risk of hyperkalaemia and hepatotoxicity, respectively.

Impact of Prophylactic Trimethoprim-Sulfamethoxazole on Clearance of High-Dose Methotrexate in Adult Patients.

PURPOSE: High-dose methotrexate (HDMTX) is an antineoplastic dosing strategy used to treat various cancers including primary central nervous system lymphoma. Trimethoprim-sulfamethoxazole (TMP/SMX) is commonly used for antibiotic prophylaxis against Pneumocystis pneumonia infections in this patient population. Significant drug-drug interactions between TMP/SMX and methotrexate (MTX) leading to adverse outcomes have been documented, primarily in adult patients taking MTX for rheumatologic conditions. METHODS: This study is a single-center, retrospective, cohort study comparing outcomes in patients where TMP/SMX was held during HDMTX and patients who received concurrent prophylactic TMP/SMX during treatment. The primary end point was mean MTX level at 24, 48, and 72 hours. Secondary end points included rate of nonhematologic toxicity, rate of hematologic toxicity, median days to MTX clearance, and frequency of glucarpidase utilization. RESULTS: In total, 248 cycles of HDMTX were analyzed from 221 individual patients. One hundred ninety-one cycles were administered without prophylactic TMP/SMX, and 57 were administered with TMP/SMX. The median MTX level at 24, 48, and 72 hours in those without versus with prophylactic TMP/SMX was 4.30 versus 4.30, 0.29 versus 0.30, and 0.14 versus 0.15, respectively. Similarly, rates of hematologic and nonhematologic toxicities did not differ significantly between groups with the exception of neutropenia; however, there was no corresponding increased rate of neutropenic fever. Only one patient received glucarpidase and had not received TMP/SMX. CONCLUSION: Prophylactic TMP/SMX had minimal interaction with HDMTX and does not lead to increased time to clearance or clinically relevant toxicities. Prophylactic TMP/SMX can be safely administered with HDMTX in adult patients.

Safety and efficacy of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnant women with HIV from Gabon and Mozambique: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The cornerstone of malaria prevention in pregnancy, intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine, is contraindicated in women with HIV who are receiving co-trimoxazole prophylaxis. We assessed whether IPTp with dihydroartemisinin-piperaquine is safe and effective in reducing the risk of malaria infection in women with HIV receiving co-trimoxazole prophylaxis and antiretroviral drugs. METHODS: For this randomised, double-blind, placebo-controlled clinical trial, women with HIV attending the first antenatal care clinic visit, resident in the study area, and with a gestational age up to 28 weeks were enrolled at five sites in Gabon and Mozambique. Participants were randomly assigned (1:1) to receive either IPTp with dihydroartemisinin-piperaquine at each scheduled antenatal care visit plus daily co-trimoxazole (intervention group) or placebo at each scheduled antenatal care visit plus daily co-trimoxazole (control group). Randomisation was done centrally via block randomisation (block sizes of eight), stratified by country. IPTp was given over 3 days under direct observation by masked study personnel. The number of daily IPTp tablets was based on bodyweight and according to the treatment guidelines set by WHO (target dose of 4 mg/kg per day [range 2-10 mg/kg per day] of dihydroartemisinin and 18 mg/kg per day [range 16-27 mg/kg per day] of piperaquine given once a day for 3 days). At enrolment, all participants received co-trimoxazole (fixed combination drug containing 800 mg trimethoprim and 160 mg sulfamethoxazole) for daily intake. The primary study outcome was prevalence of peripheral parasitaemia detected by microscopy at delivery. The modified intention-to-treat population included all randomly assigned women who had data for the primary outcome. Secondary outcomes included frequency of adverse events, incidence of clinical malaria during pregnancy, and frequency of poor pregnancy outcomes. All study personnel, investigators, outcome assessors, data analysts, and participants were masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT03671109. FINDINGS: From Sept 18, 2019, to Nov 26, 2021, 666 women (mean age 28·5 years [SD 6·4]) were enrolled and randomly assigned to the intervention (n=332) and control (n=334) groups. 294 women in the intervention group and 308 women in the control group had peripheral blood samples taken at delivery and were included in the primary analysis. Peripheral parasitaemia at delivery was detected in one (<1%) of 294 women in the intervention group and none of 308 women in the control group. The incidence of clinical malaria during pregnancy was lower in the intervention group than in the control group (one episode in the intervention group vs six in the control group; relative risk [RR] 0·12, 95% CI 0·03-0·52, p=0·045). In a post-hoc analysis, the composite outcome of overall malaria infection (detected by any diagnostic test during pregnancy or delivery) was lower in the intervention group than in the control group (14 [5%] of 311 women vs 31 [10%] of 320 women; RR 0·48, 95% CI 0·27-0·84, p=0·010). The frequency of serious adverse events and poor pregnancy outcomes (such as miscarriages, stillbirths, premature births, and congenital malformations) did not differ between groups. The most frequently reported drug-related adverse events were gastrointestinal disorder (reported in less than 4% of participants) and headache (reported in less than 2% of participants), with no differences between study groups. INTERPRETATION: In the context of low malaria transmission, the addition of IPTp with dihydroartemisinin-piperaquine to co-trimoxazole prophylaxis in pregnant women with HIV did not reduce peripheral parasitaemia at delivery. However, the intervention was safe and associated with a decreased risk of clinical malaria and overall Plasmodium falciparum infection, so it should be considered as a strategy to protect pregnant women with HIV from malaria. FUNDING: European and Developing Countries Clinical Trials Partnership 2 (EDCTP2) and Medicines for Malaria Venture. TRANSLATIONS: For the Portuguese and French translations of the abstract see Supplementary Materials section.

Observational study of the clinical utility of sulfamethoxazole serum level monitoring in the treatment of brain abscesses due to Nocardia species.

ABSTRACT: Although there is a lack of data in trimethoprim-sulfamethoxazole (TMP-SMX) serum monitoring utility for invasive nocardial infections, therapeutic drug monitoring is widely used to optimize dosing and avoid adverse reactions that may cause treatment interruption.We retrospectively reviewed all adults who received TMP-SMX to treat nocardial brain abscess and had SMX serum level testing from 2010 to 2020.Twenty-two patients received treatment with TMP-SMX for Nocardia species brain abscess and 16 (72.7%) had a reported SMX level, with a median patient age of 65.5 years (interquartile range, IQR 59.5-72.5). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a shorter median course of TMP-SMX treatment (322 days [IQR 188-365] vs. 365 [IQR 224-365]; P = .31) and higher therapeutic induction dose (10 [62.5%] vs. 3 [50%]; P = .92). Similarly, they were more frequently on hemodialysis (3 [13.6%] vs. 1 [4.5%]; P = > .99). The median peak level was 158.5 (IQR 120-218) µg/mL, collected at 2 hours (75%) post-administration in the induction phase (81.3%). Patients with documented SMX levels had fewer reported drug toxicity (5 [31.3%] vs. 4 [66.7%]; P = .1) than those without SMX levels. Among the five patients who reported TMP-SMX-related toxicity, 4 (80%) had an SMX peak level >150 µg/mL. There was no difference in the cure, relapse, and death rates among the two groups.While SMX level was not associated with Nocardia species brain abscess cure rates and mortality, most patients with SMX peak >150 µg/mL experienced drug toxicity.

Acute exacerbation of pulmonary toxoplasmosis during corticosteroid therapy for immune thrombocytopenia: A case report and literature review.

RATIONALE: Pulmonary toxoplasmosis (PT) is an infectious disease that can be fatal if reactivation occurs in the recipients of hematopoietic stem cell transplantation (HSCT) who were previously infected with Toxoplasma gondii. However, whether the toxoplasmosis reactivation is an actual risk factor for patients receiving immunosuppressive therapies without HSCT remains unclear. Therefore, reactivated PT is not typically considered as a differential diagnosis for pneumonia other than in patients with HSCT or human immunodeficiency virus (HIV). PATIENT CONCERNS: A 77-year-old man presented with fever and nonproductive cough for several days. He was hospitalized due to atypical pneumonia that worsened immediately despite antibiotic therapy. Before 4 months, he was diagnosed with immune thrombocytopenia (ITP) and received corticosteroid therapy. Trimethoprim-sulfamethoxazole (ST) was administered to prevent pneumocystis pneumonia resulting from corticosteroid therapy. DIAGNOSIS: The serological and culture test results were negative for all pathogens except T. gondii immunoglobulin G antibody. Polymerase chain reaction, which can detect T. gondii from frozen bronchoalveolar lavage fluid, showed positive results. Therefore, he was diagnosed with PT. INTERVENTION: ST, clindamycin, and azithromycin were administered. Pyrimethamine and sulfadiazine could not be administered because his general condition significantly worsened at the time of polymerase chain reaction (PCR) examination. OUTCOMES: The patient died of acute respiratory distress syndrome despite anti-T. gondii treatment. An autopsy revealed a severe organizing pneumonia and a small area of bronchopneumonia. LESSONS: PT should be considered as a differential diagnosis in patients with pneumonia, particularly in seropositive patients who receive immunosuppressive therapies even for other than HSCT or HIV.

Estimation of lifetime survival and predictors of mortality among TB with HIV co-infected children after test and treat strategies launched in Northwest, Ethiopia, 2021; a multicentre historical follow-up study.

INTRODUCTION: In resource-limited settings, the mortality rate among tuberculosis and human Immunodeficiency virus co-infected children is higher. However, there is no adequate evidence in Ethiopia in general and in the study area in particular. Hence, this study aims to estimate lifetime survival and predictors of mortality among TB with HIV co-infected children after test and treat strategies launched in Northwest Ethiopia Hospitals, 2021. METHODS: Institution-based historical follow-up study was conducted in Northwest Ethiopia Hospitals among 227 Tuberculosis and Human Immunodeficiency Virus co-infected children from March 1, 2014, to January 12, 2021. The data were entered into Epi info-7 and then exported to STATA version 14 for analysis. The log-rank test was used to estimate the curve difference of the predictor variables. Bivariable cox-proportional hazard models were employed for each predictor variable. Additionally, those variables having a p-value < 0.25 in bivariate analysis were fitted into a multivariable cox-proportional hazards model. P-value < 0.05 was used to declare significance associated with the dependent variable. RESULTS: From a total of 227 TB and HIV co-infected children, 39 died during the follow-up period. The overall mortality rate was 3.7 (95% CI (confidence interval): 2.9-4.7) per 100 person-years with a total of 1063.2-year observations. Cotrimoxazole preventive therapy (CPT) non-users [Adjusted Hazarded Ratio (AHR) = 3.8 (95% CI: 1.64-8.86)], presence of treatment failure [AHR = 3.0 (95% CI: 1.14-78.17)], and Cluster of differentiation 4(CD4) count below threshold [AHR = 2.7 (95% CI: 1.21-6.45)] were significant predictors of mortality. CONCLUSION: In this study, the mortality rate among TB and HIV co-infected children was found to be very high. The risk of mortality among TB and HIV co-infected children was associated with treatment failure, CD4 count below the threshold, and cotrimoxazole preventive therapy non-users. Further research should conduct to assess and improve the quality of ART service in Northwest Ethiopia Hospitals.

Relay oral therapy in febrile urinary tract infections caused by extended spectrum beta-lactamase-producing Enterobacteriaceae in children: A French multicenter study.

OBJECTIVES: We need studies assessing therapeutic options for oral relay in febrile urinary tract infection (FUTI) due to ESBL-producing Enterobacteriaceae (ESBL-E) in children. Amoxicillin-clavulanate/cefixime (AC-cefixime) combination seems to be a suitable option. We sought to describe the risk of recurrence at 1 month after the end of treatment for FUTI due to ESBL-E according to the oral relay therapy used. MATERIALS AND METHODS: We retrospectively identified children <18 years who were included in a previous prospective observational multicentric study on managing FUTI due to ESBL-E between 2014 and 2017 in France. We collected whether children who received cotrimoxazole, ciprofloxacin or the AC-cefixime combination as the oral relay therapy reported a recurrence within the first month after the end of treatment. Then, we analyzed the susceptibility drug-testing of the strains involved. RESULTS: We included 199 children who received an oral relay therapy with cotrimoxazole (n = 72, 36.2%), ciprofloxacin (n = 38, 19.1%) or the AC-cefixime combination (n = 89, 44.7%). Nine (4.5%) patients had a recurrence within the first month after the end of treatment, with no difference between the 3 groups of oral relay (p = 0.8): 4 (5.6%) cotrimoxazole, 2 (5.3%) ciprofloxacin and 3 (3.4%) AC-cefixime combination. Phenotype characterization of 249 strains responsible for FUTI due to ESBL-E showed that 97.6% were susceptible to the AC-cefixime combination. CONCLUSIONS: The AC-cefixime combination represents an interesting therapeutic option for oral relay treatment of FUTI due to ESBL-E as the recurrence rate at 1 month after the end of treatment was the same when compared to cotrimoxazole and ciprofloxacin.

Validity of caregivers' reports on prior use of antibacterials in children under five years presenting to health facilities in Gulu, northern Uganda.

INTRODUCTION: Given the frequent initiation of antibacterial treatment at home by caregivers of children under five years in low-income countries, there is a need to find out whether caregivers' reports of prior antibacterial intake by their children before being brought to the healthcare facility are accurate. The aim of this study was to describe and validate caregivers' reported use of antibacterials by their children prior to seeking care at the healthcare facility. METHODS: A cross sectional study was conducted among children under five years seeking care at healthcare facilities in Gulu district, northern Uganda. Using a researcher administered questionnaire, data were obtained from caregivers regarding reported prior antibacterial intake in their children. These reports were validated by comparing them to common antibacterial agents detected in blood and urine samples from the children using liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods. RESULTS: A total of 355 study participants had a complete set of data on prior antibacterial use collected using both self-report and LC-MS/MS. Of the caregivers, 14.4% (51/355, CI: 10.9-18.5%) reported giving children antibacterials prior to visiting the healthcare facility. However, LC-MS/MS detected antibacterials in blood and urine samples in 63.7% (226/355, CI: 58.4-68.7%) of the children. The most common antibacterials detected from the laboratory analysis were cotrimoxazole (29%, 103/355), ciprofloxacin (13%, 46/355), and metronidazole (9.9%, 35/355). The sensitivity, specificity, positive predictive value (PPV), negative predictive value and agreement of self-reported antibacterial intake prior to healthcare facility visit were 17.3% (12.6-22.8), 90.7% (84.3-95.1), 76.5% (62.5-87.2), 38.5% (33.0-44.2) and 43.9% (k 0.06) respectively. CONCLUSION: There is low validity of caregivers' reports on prior intake of antibacterials by these children. There is need for further research to understand the factors associated with under reporting of prior antibacterial use.

Cerebral nocardiosis with osteomyelitis of skull vault complicating a primary neck lesion in an immunocompetent patient: a case report.

Nocardia infection is an uncommon and rare condition in immunocompetent patient. A case of cutaneous nocardiosis complicated with osteomyelitis of the vault scalp in a 64-year-old man, with no remarkable past medical history, is reported. Treatment with trimethoprime-sulfamethoxazole than doxycycline for 12 months led to complete resolution and no evidence of recurrence was noted. Nocardia infection should be considered even in immunocomptent patients and doxycycline is a good alternative for treatment.

Pneumocystis jiroveci pneumonia with cytomegalovirus infection diagnosed by metagenomic next-generation sequencing in a patient with nephrotic syndrome: A case report.

INTRODUCTION: Opportunistic infection with multiple pathogens currently has become less uncommon since the application of immunosuppressant or corticosteroid in non- Human immunodeficiency virus patients. However, the clinical diagnosis of the co-infection remains difficult since the uncertainty and deficiency of the microbiologic testing methods. PATIENT CONCERNS: A 66-year-old male patient was admitted to our hospital with chest stuffiness, shortness of breath and elevated body temperature. DIAGNOSIS: He was diagnosed with the co-infection of Pneumocystis jiroveci and cytomegalovirus by metagenomic next-generation sequencing of bronchoalveolar lavage fluid after bronchoscopy. INTERVENTIONS: The patient was empirically treated with broad-spectrum antibiotics, trimethoprim/ sulfamethoxazole and ganciclovir in the beginning of the admission. OUTCOMES: The condition of this patient was not improved even with the intervention at the early stage of the disease. His family requested discharge after 24 inpatient days. LESSONS: This case highlights the application of metagenomic next-generation sequencing in the clinical diagnosis of pulmonary co-infection. Suitable prophylaxis, necessary clinical awareness and accurate diagnosis are indispensable for immunocompromised patients with pulmonary infection.

Effect of 7 vs 14 Days of Antibiotic Therapy on Resolution of Symptoms Among Afebrile Men With Urinary Tract Infection: A Randomized Clinical Trial.

Importance: Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness. Objective: To determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized. Interventions: Participants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment. Main Outcomes and Measures: The prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication. Results: Among 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, -5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, -5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, -3.0% [95% CI, -10.8% to 6.2%]; P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group. Conclusions and Relevance: Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI. Trial Registration: ClinicalTrials.gov identifier: NCT01994538.

Effectiveness and safety evaluation of thrice weekly double strength vs daily single strength trimethoprim-sulfamethoxazole for prophylaxis of pneumocystis jirovecii pneumonia after kidney transplantation: a two year prospective cohort study.

PURPOSE: It is hard for clinicians to choose the best regimen for pneumocystis jirovecii pneumonia (PJP) prophylaxis. The aim is to evaluate the effectiveness and safety of thrice weekly double strength (TWDS) vs daily single strength (DSS) trimethoprim-sulfamethoxazole (TMP-SMX) for prophylaxis of PJP after kidney transplantation. METHODS: Adult renal transplant recipients (RTRs) who were transplanted between January 1, 2015 and July 1, 2018 were evaluated. A total of 189 RTRs were prescribed PJP prophylactic regimen during the study period (TWDS group: n=98; DSS group: n=91). RESULTS: Morbidity due to PJP infection was significantly higher in TWDS group as compared with DSS group (8.60% vs 1.14%, p= 0.021). There was a significant trend toward higher prevalence of confirmed PJP (log-rank=0.021) in TWDS group. The use of DDS TMP-SMX for prophylaxis after kidney transplantation was associated with a 79% reduction in the incidence of PJP comparing the prophylactic regimen of TWDS. There was no significant difference between the two groups in the overall rate of premature TMP-SMX discontinuation and laboratory indexes. CONCLUSION: Six months of DSS TMP-SMX prophylaxis was more effective than TWDS TMP-SMX regimen with the same safety profile.

Egg residue and depletion in Rhode Island Red hens (Gallus gallus domesticus) following multiple oral doses of trimethoprim-sulfamethoxazole.

Sulfamethoxazole-Trimethoprim residues in eggs can cause risks to human health. The most common cause of residues in eggs results from failure to meet an appropriate withdrawal interval. The aim of this study was to determine the quantity and duration of sulfamethoxazole-trimethoprim residues in eggs and evaluate the drug elimination parameters in egg components and whole egg to better estimate the withdrawal interval of sulfamethoxazole and trimethoprim following oral administration for 7 days at a purposed dosage regimen (time average 46 mg kg-1 day-1 for sulfamethoxazole, time average 25 mg kg-1 day-1 for trimethoprim). Residues of sulfamethoxazole and trimethoprim in albumen and yolk were analyzed by ultra-performance liquid chromatography mass spectrometry. A greater percentage of sulfamethoxazole was distributed into the albumen (91.53-96.74%) and a greater percentage of trimethoprim was distributed into yolk (63.92-77.36%) during treatment. The residues levels in whole egg declined below or reached the limit of quantification until 13 days for SMZ and TMP respectively. The withdrawal interval for SMZ and TMP were 43 days and 17 days respectively using the FDA tolerance method.

[Not all cases of groundglas opacity are COVID-19 - Pneumocystis-jirovecii-pneumonia as a differential diagnosis]. / Nicht alles Milchglas ist COVID-19 ­ Pneumocystis-jirovecii-Pneumonie als Differenzialdiagnose.

HISTORY AND CLINICAL FINDINGS: A 68-year-old male patient with psorias and a bullous pemphigoid as an underlying disease developed bilateral groundglass opacities on chest CT under longer-term, higher-dose immunosuppressive therapy with methylprednisolone with clinical symptoms of dry cough, progressive dyspnea and fever. DIAGNOSIS AND THERAPY: After the exclusion of COVID-19, Pneumocystis jirovecii pneumonia (PCP) was detected and a corresponding high-dose therapy with trimethoprim-sulfamethoxazole was initiated promptly. COURSE: Nonetheless, a complicated course with bacterial superinfection and pulmonary aspergillosis as well as ARDS developed. DISCUSSION AND CONCLUSION: In contrast to COVID-19, the typical course, diagnosis and therapy of Pneumocystitis jirovecii pneumonia are discussed. It is particularly emphasized that not all ground glass infiltrates in the CT chest image can be traced back to a COVID-19, even in a pandemic situation. Possible differential diagnoses should always be considered and taken into account in the diagnosis.

Efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of pneumocystis pneumonia in human immunodeficiency virus-negative immunodeficient patients: A systematic review and meta-analysis.

BACKGROUND: Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine. METHODS: A comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported. RESULTS: Of the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03). CONCLUSIONS: TMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.

Chronic cystoisosporiasis in an immunocompetent adult: A case report.

RATIONALE: Cystoisosporiasis is an intestinal infectious disease caused by a coccidian protozoa, Cystoisospora belli (C. belli). It can cause prolonged and refractory diarrhea most commonly in immunocompromised patients, while immunocompetent individuals usually exhibit no symptoms or self-limited diarrhea. PATIENT CONCERNS: We herein report a case of chronic cystoisosporiasis in an immunocompetent patient. A 62-year-old man, who had been first diagnosed with cystoisosporiasis 15 years ago and had been treated with oral administration of trimethoprim-sulfamethoxazole (TMP-SMX), complained of persistent watery diarrhea. He was negative for anti-human immunodeficiency virus antibody and anti-human T-cell leukemia virus type 1 (HTLV-1) antibody. DIAGNOSIS: Biopsy specimens from the duodenum revealed oocysts in the atrophic absorptive epithelium and protozoa were detected through stool examination, indicating the recurrence of cystoisosporiasis. Capsule endoscopy showed diffuse atrophic mucosa with white villi in the entire small intestine. We diagnosed him with chronic cystoisosporiasis that occurred in an immunocompetent adult. INTERVENTIONS: Since oral administration of TMP-SMX and ciprofloxacin were ineffective, the intravenous administration of TMP-SMX was initiated. OUTCOMES: Intravenous TMP-SMX exhibited a significant improvement. LESSONS: This case indicates that even immunocompetent individuals may develop recurrent and refractory cystoisosporiasis. Furthermore, intravenous treatment of antibiotic agents should be considered when the impaired absorptive ability from the small intestine is suspected.

Is cotrimoxazole prophylaxis against Pneumocystis jirovecii pneumonia needed in patients with systemic autoimmune rheumatic diseases requiring immunosuppressive therapies?

The incidence of Pneumocystis jirovecii pneumonia (PJP) has increased over recent years in patients with systemic autoimmune rheumatic diseases (SARD). PJP prognosis is poor in those receiving immunosuppressive therapy and glucocorticoids in particular. Despite the effectiveness of cotrimoxazole against PJP, the risk of adverse effects remains significant, and no consensus has emerged regarding the need for PJP prophylaxis in SARD patients undergoing immunosuppressor therapies.Objective: To evaluate the efficacy and safety of cotrimoxazole prophylaxis against PJP in SARD adult patients receiving immunosuppressive therapies. Methods: We performed a systematic review, consulting MEDLINE, EMBASE, and Cochrane Library databases up to April 2020. Outcomes covered prevention of PJP, other infections, morbidity, mortality, and safety. The information obtained was summarized with a narrative review and results were tabulated. Of the 318 identified references, 8 were included. Two were randomized controlled trials and six observational studies. The quality of studies was moderate or low. Despite disparities in the cotrimoxazole prophylaxis regimens described, results were consistent in terms of efficacy, particularly with glucocorticoid doses > 20 mg/day. However, cotrimoxazole 400 mg/80 mg/day, prescribed three times/ week, or 200 mg/40 mg/day or in dose escalation, exhibited similar positive performances. Conversely, cotrimoxazole 400 mg/80 mg/day showed higher incidences of withdrawals and adverse effects. Cotrimoxazole prophylaxis against PJP exhibited efficacy in SARD, mainly in patients taking glucocorticoids ≥ 20 mg/day. All cotrimoxazole regimens exposed seemed equally efficacious, although, higher quality trials are needed. Adverse effects were observed 2 months after initiation, particularly with the 400 mg/80 mg/day regimen. Conversely, escalation dosing or 200 mg/40 mg/day regimens appeared better tolerated.