Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug

ABSTRACT Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

Severe Covid-19 in pregnant and postpartum women admitted to an intensive care unit: A retrospective cohort study.

BACKGROUND: SARS-CoV-2 infection is associated with worse maternal and fetal outcomes. This study aims to describe the characteristics of pregnant and postpartum women with severe Covid-19 admitted to ICU. METHODS AND FINDINGS: It's a retrospective cohort study evaluating pregnant and postpartum women referenced to a specialized ICU between May 2020 and June 2022. Covid-19 was confirmed with RT-PCR or rapid antigen test on a nasopharyngeal swab. Variables were described by median and IQR when numerical, and by frequency and percentage when categorical. OR with 95% CI were calculated for the evaluation of factors related to death. P-values were calculated using Pearson's ꭓ2-test, Fisher's exact test, Wilcoxon rank sum test, and Kruskall-Wallis test, and statistical significance was established as < 0·05. Missing data were excluded. All statistical analysis were performed using R software version 4.2.2. Of the 101 admissions, 85 (84·2%) were of pregnant women. Obesity (23·0%) and systemic arterial hypertension (13·0%) were the most prevalent medical conditions. Sixty-six (65·3%) were admitted using some type of oxygen support. Forty-seven (46·5%) evolved to mechanical ventilation. There were 61 events considered obstetric complications, with 8 stillbirths/fetal losses. The overall lethality was 15·8%. Pregnancy interruption, need for non-invasive mechanical ventilation, level of oxygen support at admission, prone maneuver, hemodialysis, and healthcare-related infections were factors associated with death. Evaluating the WHO 7-category ordinary scale, there was a trend of increase in the risk of death with higher punctuation, with a statistically significant difference of women with 5 (OR = 7·27; 95% IC = 1·17-194; p = 0·031) or 6 points (OR = 12·0; 95% IC = 1·15-391; p = 0·038) when compared to the ones with 3 points, i.e., of women admitted with a high-flow non-rebreathing mask or invasive mechanical ventilation, compared with the ones admitted at room air, respectively. The main limitations of this study are the relatively small number of participants, and the use of data derived of medical records-which are susceptible to misclassification and variable amounts of missing data. CONCLUSIONS: Pregnant and postpartum women with severe Covid-19 have high lethality and a high incidence of clinical and obstetric complications. These findings support that this population should be prioritized in public health strategies that address Covid-19.

Factors associated with the development of Congenital Zika Syndrome: a case-control study.

BACKGROUND: We aim to investigate possible maternal- and pregnancy-related factors associated with the development of Congenital Zika Syndrome (CZS) in children of mothers with probable gestational infection. METHODS: This case-control study, we recruited mother-infant pairs between May 2015 and October 2017 in a pediatric infectious disease clinic in Rio de Janeiro. Inclusion criteria required either that the mother reported Zika infection symptoms during pregnancy or that the infant presented with clinical or imaging features of the CZS. Exclusion criteria included detection of an alternative cause for the patient's presentation or negative polymerase chain reaction assays for Zika in all specimens tested within 12 days from the beginning of maternal symptoms. Infants with CZS (CDC definition) were selected as cases and infants without CZS, but with probable maternal Zika virus infection during pregnancy, were selected as controls. Maternal and pregnancy-related informations were collected and their relationship to the presence of congenital anomalies due to CZS was assessed by Fisher exact or Mann-Whitney test. RESULTS: Out of the 42 included neonates, 24 (57.1%) were diagnosed with CZS (cases). The mean maternal age at the birth was 21 years old. The early occurrence of maternal symptoms during pregnancy was the only variable associated with CZS (odds ratio = 0.87, 95% CI: 0.78-0.97). Case's mothers presented symptoms until the 25th week of gestational age (GA), while control's mothers presented until 36th weeks of GA. Income; illicit drug, alcohol, or tobacco use during pregnancy; other infections during pregnancy (including previous dengue infection) were not associated with CZS. CONCLUSIONS: Our study corroborates the hypothesis that Zika virus infection earlier in pregnancy is a risk factor to the occurrence of congenital anomalies in their fetuses.