Trimethoprim-sulfamethoxazole Treatment Research Articles

Outcomes of low-dose trimethoprim-sulfamethoxazole treatment in patients with non-HIV pneumocystis pneumonia: A nationwide Japanese retrospective cohort study

ObjectivesLow-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be a treatment option for patients with Pneumocystis jirovecii pneumonia (PCP). However, its effectiveness in patients without human immunodeficiency virus (HIV) infection has yet to be thoroughly investigated. MethodsThis retrospective cohort study used data extracted from the Japanese Diagnosis Procedure Combination inpatient database. We included immunocompromised patients without HIV having been diagnosed with PCP and had started TMP-SMX treatment between July 2010 and March 2022. We divided eligible patients into conventional-dose (15.0–20.0 mg/kg/d) and low-dose (7.5–15.0 mg/kg/d) groups and performed propensity-score overlap-weighting analysis. The primary outcome was in-hospital mortality rate. Secondary outcomes were completion of the initial treatment and use of alternatives to TMP-SMX for PCP treatment during hospitalization. ResultsAmong 4449 eligible patients, 1682 (37.8 %) and 2767 (62.2 %) received conventional- and low-dose TMP-SMX treatments, respectively. No significant difference was observed in in-hospital mortality (risk difference, −1.4 %; 95 % CI, −4.5–1.7 %; P = 0.388). Low-dose TMP-SMX was associated with increased completion of initial treatment (risk difference, 4.6 %; 95 % CI, 2.3–6.9 %; P < 0.001), and reduced use of alternative agents (risk difference, −4.0 %; 95 % CI, −7.4 to −0.6 %; P = 0.020). ConclusionLow-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

Bartonella Henselae Related Unilateral Anterior Uveitis and Subsequent Multifocal Retinitis in a Case Under Certolizumab Treatment.

A case of ocular bartonellosis under anti-tumour necrosis factor treatment is described. A 29-year-old woman with psoriasis who had been on certolizumab treatment was examined with a left visual deterioration following a fever bout, malaise, and placoid erythematous rashes on her neck. As there was acute anterior uveitis in her left eye, it was recommended to stop certolizumab treatment for a possible infectious aetiology. However, her physician elected to continue the certolizumab treatment. Ten days later, the patient noticed further visual decline despite the topical steroid treatment. This time, there were scattered yellow-white small retinitis foci at the left posterior pole. Infectious agents were searched and while Bartonella henselae antibodies were negative for immunoglobulin M, the immunoglobulin G titre was 1/80. Clinical findings were improved with the systemic treatment of oral trimethoprim-sulfamethoxazole (160/800 mg twice daily for six weeks) and azithromycin (500 mg once daily for two weeks). Though extremely rare, ocular bartonellosis should be kept in mind in patients on anti-tumour necrosis factor treatment as rapid and accurate diagnosis may end up with an excellent visual outcome and full recovery. Anti-tumour necrosis factor treatment is fraught with several ocular side effects including myositis, corneal infiltrates, scleritis, uveitis, optic neuritis, retinal vasculitis and ophthalmoplegia.When a new uveitis episode occurs in cases undergoing anti-tumour necrosis factor therapy, its cause poses a diagnostic challenge as it can have either an infectious or a non-infectious nature.Though very rare, ocular bartonellosis may also occur in immunocompromised individuals and a prompt diagnosis and appropriate treatment can lead to an excellent visual recovery.

In Vivo Genotoxicity and Cytotoxicity Kinetics of Trimethoprim Sulfamethoxazole in Well-nourished and Undernourished Young Rats.

Undernutrition is a serious health problem prevalent in poor countries, affecting millions of people worldwide, especially young children, pregnant women, and sick elderly individuals. This condition increases vulnerability to infections, leading to widespread use of antibiotic treatments in undernourished populations. The objective of the present study was to determine the in vivo genotoxic and cytotoxic effects of trimethoprim-sulfamethoxazole (TMP-SMX) treatment according to nutritional conditions. The effects of TMP-SMX treatment were measured by analyzing the kinetics of micronucleated reticulocytes (MN-RET) induced in the peripheral blood of young, well-nourished (WN) and undernourished (UN) rats. In the WN group, two distinct peaks of MN-RET were observed, while the UN group had a significantly higher basal frequency of MN-RET compared to the WN group and only a later peak. Reticulocyte (RET) frequency slightly decreased in WN, indicating a poor cytotoxic effect. In contrast, in the UN, the treatment caused a significant increase in RET frequency. The results indicate that SMX's aromaticity index decreases when formed with TMP, suggesting potentially fewer toxic effects. In vivo TMP-SMX produces two MN-RET induction peaks in WN animals, indicating two DNA damage induction mechanisms and consequent micronucleus production. The UN rats did not display the two peaks, indicating that the first MN induction mechanism did not occur in UN, possibly due to pharmacokinetic effects, decreased metabolism or effects on cell proliferation. TMP-SMX has a slight cytotoxic effect on WN. In contrast, in the UN, the antibiotic treatment seems to favor early erythropoiesis.

Prognostic Factors of In-hospital Mortality in Patients without Human Immunodeficiency Virus Infection with Pneumocystis Pneumonia: A Retrospective Cohort Study.

Objective This study explored the prognostic factors of in-hospital mortality in patients with Pneumocystis pneumonia (PCP) without human immunodeficiency virus (HIV) infection, using a Japanese nationwide inpatient database. Methods We extracted the data of patients with PCP without HIV infection between July 2010 and March 2022 from the Diagnosis Procedure Combination database. We performed multivariable logistic regression analyses to identify the prognostic factors of in-hospital mortality in with PCP without HIV infection. Results We identified 1,704 patients with PCP without HIV infection and 404 (23.7%) in-hospital deaths. Higher in-hospital mortality was associated with advanced age, male sex (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06-2.00), a low Barthel index score, non-hematological malignancy (OR, 1.81; 95% CI, 1.22-2.70), receipt of mechanical ventilation (OR, 2.49; 95% CI, 1.47-4.21), and administration of antibiotics (OR, 1.52; 95% CI, 1.12-2.06) and antifungal drugs (OR, 1.83; 95% CI, 1.26-2.67). Lower in-hospital mortality was associated with connective tissue disease and vasculitis (OR, 0.55; 95% CI, 0.37-0.81), hematological malignancy (OR, 0.59; 95% CI, 0.38-0.93), and early trimethoprim-sulfamethoxazole treatment (OR, 0.63; 95% CI, 0.44-0.90). Conclusions These findings will help physicians identify patients who may benefit from early aggressive therapeutic interventions.

2738. Two-step sulfonamide antibiotic challenges in patients who require treatment with trimethoprim-sulfamethoxazole at an academic medical center: Outcomes in a largely immunocompromised population

Abstract Background Sulfonamide antibiotic allergy is the second most reported medication allergy. The allergy label limits the use of trimethoprim-sulfamethoxazole (TMP-SMX), the antibiotic of choice for pneumocystis jirovecii pneumonia (PJP), Toxoplasma, and many types of urinary tract infections. Immunocompromised patients, including solid organ transplant recipients, are considered to be at a higher risk for developing an infection. While penicillin allergies are commonly tested and patients delabeled, sulfonamide challenges are not as prevalent. Patients who are tested following a transplant may be on medications that lower the negative predictive value of the challenge, raising questions about whether they truly passed the challenge or whether mild reactions were masked. Methods: Thirty-seven patients labeled with a sulfonamide allergy who were evaluated and challenged with two doses of TMP-SMX were included. Adults (≥18 years) with a sulfonamide antibiotic allergy were evaluated and challenged between June 2020 and May 2023. Data collection included the number of patients challenged and delabeled, number of patients who had reactions and what type of reaction, and proportion of patients who completed the treatment or prophylaxis course for which TMP-SMX was the first-line antibiotic. Results Thirty-seven patients were challenged, of which twenty-seven patients were immunocompromised (73%). Thirty-four (92%) passed the sulfonamide challenge and were delabeled, and thirty-two (86%) completed the full course of TMP-SMX prophylaxis or treatment. Nineteen patients (51%) were tested following immunosuppression or antihistamine treatment due to a new transplant. Five patients were not able to be delabeled due to mild or delayed reactions to the challenge or treatment, including two patients that passed the sulfonamide challenge and were delabeled but had a mild reaction during SMX-TMP therapy and were relabeled. Conclusion The benefits of sulfonamide antibiotic allergy testing can have great effects in immunocompromised patients in preventing the use of second-line antibiotics. Sulfonamide challenges were shown to be safe and effective in immunocompromised patients in delabeling the sulfonamide antibiotic allergy and leading to the completion of treatment with TMP-SMX. Disclosures Shyam Joshi, MD, Cogent: Honoraria|Leo Pharma: Honoraria|Nectar Allergy: Advisor/Consultant|Nectar Allergy: Stocks/Bonds|Sanofi/Regeneron: Advisor/Consultant|Sanofi/Regeneron: Honoraria|Takeda: Honoraria

Clinical significance of mutations in dihydropteroate synthase in Pneumocystis jirovecii pneumonia among non-HIV-infected patients

BackgroundDihydropteroate synthase (DHPS) mutations may be associated with trimethoprim-sulfamethoxazole resistance in Pneumocystis jirovecii pneumonia (PCP) and worse clinical outcomes. However, the clinical significance of DHPS mutations in PCP among non-human immunodeficiency virus (HIV)-infected patients remains unclear. MethodsPatients with PCP in three tertiary referral hospitals in Taiwan between 2016 and 2020 were retrospectively enrolled. Two point mutations, Thr55Ala and Pro57Ser, in the DHPS protein were analysed. Patients with invalid DHPS mutations in the respiratory specimen, chronic respiratory failure, receiving endotracheal intubation for surgical intervention, HIV infection, Pneumocystis jirovecii colonisation, and no lactate dehydrogenase (LDH) data were excluded. The primary outcome was 30-day survival. ResultsA total of 215 patients were analysed. Mutants inside DHPS were found in 78 patients (36.3%) and 68 patients (31.6%) died within 30 days. A total of 214 patients (99.5%) received trimethoprim-sulfamethoxazole as the first-line treatment. The rates of mechanical ventilation, 30-day, and in-hospital mortality were similar between wild-type and mutant DHPS PCP. After adjusting for important confounders, LDH > 500 µ/L (adjusted hazard ratio [aHR] = 2.448, P = 0.001), pneumonia severity index > 135 mg/dL (aHR = 1.689, P = 0.049), and having solid tumours (aHR = 1.832, P = 0.034) were independently associated with higher mortality. In subgroup analysis, mutant DHPS PCP patients had less 30-day mortality among patients aged > 65 years (P = 0.049), with lymphopenia (P = 0.040), and those without solid tumour (P = 0.045). ConclusionsIn non-HIV-infected PCP, point mutants inside DHPS may not be associated with trimethoprim-sulfamethoxazole treatment outcomes. Further prospective large-scale studies are warranted.

Gut Microbiota-Mediated Pharmacokinetic Drug-Drug Interactions between Mycophenolic Acid and Trimethoprim-Sulfamethoxazole in Humans.

Mycophenolic acid (MPA) and trimethoprim-sulfamethoxazole (TMP-SMX) are commonly prescribed together in certain groups of patients, including solid organ transplant recipients. However, little is known about the pharmacokinetic drug-drug interactions (DDIs) between these two medications. Therefore, the present study aimed to determine the effects of TMP-SMX on MPA pharmacokinetics in humans and to find out the relationship between MPA pharmacokinetics and gut microbiota alteration. This study enrolled 16 healthy volunteers to take a single oral dose of 1000 mg mycophenolate mofetil (MMF), a prodrug of MPA, administered without and with concurrent use of TMP-SMX (320/1600 mg/day) for five days. The pharmacokinetic parameters of MPA and its glucuronide (MPAG) were measured using high-performance liquid chromatography. The composition of gut microbiota in stool samples was profiled using a 16S rRNA metagenomic sequencing technique during pre- and post-TMP-SMX treatment. Relative abundance, bacterial co-occurrence networks, and correlations between bacterial abundance and pharmacokinetic parameters were investigated. The results showed a significant decrease in systemic MPA exposure when TMP-SMX was coadministered with MMF. Analysis of the gut microbiome revealed altered relative abundance of two enriched genera, namely the genus Bacteroides and Faecalibacterium, following TMP-SMX treatment. The relative abundance of the genera Bacteroides, [Eubacterium] coprostanoligenes group, [Eubacterium] eligens group, and Ruminococcus appeared to be significantly correlated with systemic MPA exposure. Coadministration of TMP-SMX with MMF resulted in a reduction in systemic MPA exposure. The pharmacokinetic DDIs between these two drugs were attributed to the effect of TMP-SMX, a broad-spectrum antibiotic, on gut microbiota-mediated MPA metabolism.

A case of deep thrombocytopenia who had successfully received prolonged trimethoprim-sulfamethoxazole treatment for Nocardiosis

A case of deep thrombocytopenia who had successfully received prolonged trimethoprim-sulfamethoxazole treatment for Nocardiosis

Initiation of anti-retroviral/Trimethoprim-Sulfamethoxazole therapy in a longitudinal cohort of HIV-1 positive individuals in Western Kenya rapidly decreases asymptomatic malarial parasitemia.

Interactions between malaria and HIV-1 have important public health implications. Our previous cross-sectional studies showed significant associations between HIV-1 positivity and malarial parasitemia with an increased risk of gametocytemia. In this follow-up longitudinal study, we evaluated these associations to determine the magnitude of asymptomatic parasitemia over time, and to examine the effects of initiating Antiretroviral Therapy (ART) together with the broad-spectrum antibiotic Trimethoprim Sulfamethoxazole (TS) on asymptomatic parasitemia. 300 adult volunteers in a malaria holoendemic region in Western Kenya were enrolled and followed for six months. The study groups were composed of 102 HIV-1 negatives, 106 newly diagnosed HIV-1 positives and 92 HIV-1 positives who were already stable on ART/TS. Blood samples were collected monthly and asymptomatic malarial parasitemia determined using sensitive 18S qPCR. Results showed significantly higher malaria prevalence in the HIV-1 negative group (61.4%) (p=0.0001) compared to HIV-1 positives newly diagnosed (36.5%) and those stable on treatment (31.45%). Further, treatment with ART/TS had an impact on incidence of asymptomatic parasitemia. In volunteers who were malaria PCR-negative at enrollment, the median time to detectable asymptomatic infection was shorter for HIV-1 negatives (149 days) compared to the HIV-1 positives on treatment (171 days) (p=0.00136). Initiation of HIV treatment among the newly diagnosed led to a reduction in malarial parasitemia (expressed as 18S copy numbers/μl) by over 85.8% within one week of treatment and a further reduction by 96% after 2 weeks. We observed that while the impact of ART/TS on parasitemia was long term, treatment with antimalarial Artemether/Lumefantrine (AL) among the malaria RDT positives had a transient effect with individuals getting re-infected after short periods. As was expected, HIV-1 negative individuals had normal CD4+ levels throughout the study. However, CD4+ levels among HIV-1 positives who started treatment were low at enrollment but increased significantly within the first month of treatment. From our association analysis, the decline in parasitemia among the HIV-1 positives on treatment was attributed to TS treatment and not increased CD4+ levels per se. Overall, this study highlights important interactions between HIV-1 and malaria that may inform future use of TS among HIV-infected patients in malaria endemic regions.

WHEN TREATING ACNE GOES WRONG: A CASE OF BACTRIM-INDUCED ARDS IN A HEALTHY YOUNG WOMAN

WHEN TREATING ACNE GOES WRONG: A CASE OF BACTRIM-INDUCED ARDS IN A HEALTHY YOUNG WOMAN

Clinical Characteristic, Diagnosis and Treatment of Acute Lymphoblastic Leukemia Combined with Pneumocystis Carinii Pneumonia in Children

To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.

Using machine learning to predict antibiotic resistance to support optimal empiric treatment of urinary tract infections

Background: Antibiotic resistance is pervasive in the Veterans’ Affairs (VA) healthcare system, with rates of fluoroquinolone and trimethoprim–sulfamethoxazole (TMP/SMX) resistance approaching 30% in E. coli urinary isolates. The efficacy of antimicrobial treatment is critically dependent on the susceptibility of the infecting pathogen; however, prescription decisions are often made empirically in practice. We analyzed susceptibility profiles of enteric gram-negative rods (Enterobacterales) from clinical urine cultures collected from ambulatory patients receiving care in VA clinics and emergency departments. Our goals were (1) to develop a predictive model to support choice of empiric antibiotics pending results of susceptibility testing and (2) to examine the relationship between past antibiotic exposures and susceptibility profiles to enhance understanding of antibiotic selective pressure. Methods: We obtained 265,076 positive cultures from 157,422 unique patients from 2015 to 2020. We trained random forest multinomial classifiers to estimate the risk of a positive urine culture isolate being resistant to the multinomial outcome: fluoroquinolone, TMP–SMX, cephalosporin, or any combination of these 3 agents. Data sources evaluated for model generation included demographics, comorbidities, trend and seasonal terms, treatment history for multiple antimicrobial treatments summarized using number of prescriptions in weekly intervals, and sample history summarized by number of resistant and susceptible cultures in weekly intervals. Using 5-fold cross validation, we assess the performance of the clinical prediction using the area under the receiver operating characteristic curve (AUC) for each multinomial outcome. In addition to prediction, we modeled the direct effect of treatment on resistance using multinomial group lasso (MGL). This method allows variable selection in variable groupings, such as all variables related to the fluoroquinolone treatment history, which allowed us to assess the effect of a patient’s complete course of treatment on resistance. Results: In cross-validation analysis, our random forest model was best at predicting outcomes with fluoroquinolone resistant phenotypes compared to non–fluoroquinolone-resistant phenotypes (Table 1). From MGL, we found that having a prescription for fluoroquinolone treatment 4–8 weeks prior to a urinalysis was positively associated with fluoroquinolone resistance and negatively associated with fluoroquinolone susceptible phenotypes (Fig. 1). Conclusions: Our results show that a patient’s sample and treatment history are highly predictive of a future resistance. Fluoroquinolone treatment is especially associated with increased risk of fluoroquinolone single- and multidrug resistances. A history of either fluoroquinolone or trimethoprim-sulfamethoxazole (TMP-SMX) treatment is a stronger indicator of a future resistant phenotype than cephalosporin or penicillin.Funding: NoneDisclosures: None

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

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.

Clinical features, treatment and risk factors for interstitial pneumonia in B-cell non-Hodgkin lymphoma patients.

BackgroundInterstitial pneumonia (IP) is a common and fatal adverse effect of rituximab-containing immunochemotherapy in lymphoma patients. Following prophylactic treatment with trimethoprim-sulfamethoxazole (TMP-SMX), the clinical features, treatment, and risk factors for IP development remain largely undefined.MethodsFrom April 2015 and April 2018, 294 patients diagnosed with CD20+ B-cell non-Hodgkin lymphoma (NHL) were included in this study. All patients received front-line RCHOP-like chemotherapy and prophylactic treatment of TMP-SMX once daily. We summarized the clinicopathologic characteristics and treatment outcomes of IP in these patients and explored the possible risk factors of IP.ResultsThe overall incidence of IP was 8.16%. Typical clinical symptoms included fever for 1–3 days in 11 patients, dyspnea in 4 patients, expectoration in 5 patients, and dry cough in 7 patients. A total of 8 patients showed no apparent symptoms. Prior to IP, the median number of chemotherapy cycles was 4. The median time for IP initiation was 63 days, and the median duration of IP treatment was 11 days. All patients recovered from IP after treatment. A total of 6 patients continued to receive chemotherapy without rituximab, and 14 patients received rituximab combined with chemotherapy. No patients experienced IP recurrence. In univariate and multivariate analysis, male, diabetes, low lymphocyte counts (<1.0×109/L) and low CD4/CD8 counts were identified as risk factors of IP. Patients with no risk factors were included in the low-risk group; 1 to 2 factors: intermediate-risk; ≥3: high-risk. The occurrence of IP differed across three groups (low risk, 0%; intermediate risk, 7%; high risk, 14.5%; P=0.059).ConclusionsThe incidence of IP was 8.16% in patients with CD20+ B-cell NHL. Males, diabetes, low absolute lymphocyte counts (ALC) (<1.0×109/L) and low CD4/CD8 were identified as risk factors of IP.

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

BackgroundSeveral 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.MethodsBetween 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.ResultsThese 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).ConclusionsThis 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.

Nocardiosis esporotricoide por Nocardia brasiliensis

Nocardia brasiliensis is a gram-positive, branched, aerobic, acid-resistant, rod-shaped bacillus that inhabits in soil, rotten organic matter and waters. Cutaneous nocardiosis in immunocompetent individuals can manifest in three different forms: actinomycetoma, superficial skin infection or lymphocutaneous infection. A case of an 85-year-old woman with an ulcerated lesion on the back of her left hand with erythematous papules in the lymphatic tract infected by N. brasiliensis is described. The microorganism was presumptively identified by conventional and inexpensive methods for a medium complexity laboratory at the species level. The morphological characteristics of colonies, the mold smell, a positive Kinyoun stain and the presence of aerial mycelium were the key tests to identify the genus. Species level identification was confirmed by mass spectrometry (MALDI-TOF MS). The trimethoprim-sulfamethoxazole treatment was effective as this agent was active in the susceptibility testing.

Skin infections in Australian Aboriginal children: a narrative review.

Summary Impetigo, scabies, cellulitis and abscesses are common in Australian Aboriginal children. These conditions adversely affect wellbeing and are associated with serious long term sequelae, including invasive infection and post‐infectious complications, such as acute post‐streptococcal glomerulonephritis and acute rheumatic fever, which occurs at the highest documented rates in the world in remote Aboriginal communities.Observational research in remote communities in northern Australia has demonstrated a high concurrent burden of scabies and impetigo and their post‐infectious complications.Few data are available for other Australian states, especially for urban Aboriginal children; however, nationwide hospital data indicate that the disparity between Aboriginal and non‐Aboriginal children in skin infection prevalence also exists in urban settings.The Australian National Healthy Skin Guideline summarises evidence‐based treatment of impetigo, scabies and fungal infections in high burden settings such as remote Aboriginal communities. It recommends systemic antibiotics for children with impetigo, and either topical permethrin or oral ivermectin (second line) for the individual and their contacts as equally efficacious treatments for scabies. β‐Lactams are the treatment of choice and trimethoprim–sulfamethoxazole and clindamycin are effective alternatives for treatment of paediatric cellulitis. Abscesses require incision and drainage and a 5‐day course of trimethoprim–sulfamethoxazole or clindamycin.Addressing normalisation of skin infections and the social determinants of skin health are key challenges for the clinician. Research is underway on community‐wide skin health programs and the role for mass drug administration which will guide future management of these common, treatable diseases.

Echinocandins as alternative treatment for HIV-infected patients with Pneumocystis pneumonia.

Treatment with trimethoprim-sulfamethoxazole for Pneumocystis pneumonia (PCP) is often associated with adverse effects. Echinocandins, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, clinical experience with echinocandins in the treatment of PCP remains limited among HIV-infected patients. From August 2013 to April 2018, data of HIV-infected patients with confirmed PCP who received echinocandins as alternative treatment because of intolerance or unresponsiveness to trimethoprim-sulfamethoxazole were retrospectively reviewed to assess the effectiveness and safety of echinocandins alone or in combination with other agents. In total, 34 patients were included, with a median CD4 count of 27 cells/μl [interquartile range (IQR), 20-93). Twenty-four patients (70.6%) presented with moderate-to-severe PCP. The most common adverse effects leading to withdrawal of trimethoprim-sulfamethoxazole were hepatotoxicity (29.4%), gastrointestinal upset (23.5%), and rash (17.6%). Nine patients (26.5%) were switched to echinocandins after failure of trimethoprim-sulfamethoxazole. The median interval before switch from trimethoprim-sulfamethoxazole to echinocandins was 9.0 days (IQR 5.0-14.0). The all-cause and PCP-related in-hospital mortality rate of patients receiving echinocandins as alternative therapy was 20.6% (7/34) and 14.7% (5/34), respectively. The all-cause in-hospital mortality was 0% in mild PCP cases and 29% (7/24) in moderate-to-severe PCP cases. Patients who had failed to respond to first-line trimethoprim-sulfamethoxazole treatment tended to have a higher in-hospital mortality rate than those without first-line trimethoprim-sulfamethoxazole failure (44.4% versus 12.0%, P = 0.06). Echinocandin therapy might serve as an alternative option for HIV-infected patients with PCP who are intolerable to trimethoprim-sulfamethoxazole.

Pnömosistis Jirovecii Enfeksiyonu Tanısı Alan Nefrotik Sendrom Olgusu

Pneumocystis jirovecii pneumonia (commonly called Pneumocystis pneumonia or PCP) is an opportunistic infection that occurs in immunocompromised individuals. 26 year-old male patient admitted to nephrology department for hypervolemic hyponatremia and consulted to our clinic because desaturation developed. He has been diagnosed with collapsing glomerulonephritis (GN) and he was using cyclosporine and prednisolone. Postero-anterior chest X-ray showed that; left cardiodiaphragmatic sinus was blunt. In the arterial blood gas, Ph:7,42 PO2:53 mmHg PCO2:35,4 mmHg, HCO3:23,6 mEql/L. The the alveolar arterial gradient was elevated (52,75). Antibiotic and because of hypervolemia diuretic therapy was recommended to the patient. After ten days the patient's hypoxia deepened.Repeated chest X-ray showed bilateral perihilar heterogeneous opacity. Flexible bronchoscopy was performed. Pneumocystis jirovecii was detected in lavage culture. The patient treated with Trimethoprim- Sulfamethoxazole (TMP-SMZ) (3 x 7.5 mg / kg) dose. Hypoxemia improved on the 7th day of treatment and the patient was discharged. TMP-SMZ treatment was completed in 21 days. Pneumocystis developing secondary to cyclosporin toxicity Jirovecii pneumonia is a rare case.

Clinical Features of Pneumocystis Jiroveci Pneumonia in Patients with Inflammatory Bowel Disease

Objective To investigate the clinical features of patients with inflammatory bowel disease (IBD) complicated with Pneumocystis Jiroveci Pneumonia (PJP). Methods We retrospectively analyzed the clinical data of 5 patients who were hospitalized in Peking Union Medical College Hospital from January 2012 to July 2017 for treatment of IBD complicated with PJP. Demographic characteristics,clinical manifestations,treatments,and outcomes were descriptively analyzed. Results Of these five patients,four had ulcerative colitis (UC) and one had Crohn's disease (CD). All patients were males,with an average age of (61.8±1.9) years. All patients were in active disease status and had symptoms including cough and suffocation. Three patients had hypoxemia,among whom two developed type 1 respiratory failure. Three patients were treated with immunosuppressive medications (corticosteroids and/or immunosuppressant drugs) before the diagnosis of PJP. Lymphocyte counts in three patients were less than 0.6×109/L. CD4+T cells in two patients were less than 200×106/L. Four patients had elevated serum cytomegalovirus DNA. The level of β-D-glucan was elevated in four patients. Chest CT showed bilateral diffuse ground glass opacification. PJP-DNA was positive in sputum or bronchoalveolar lavage fluid in all patients. Two patients with type 1 respiratory failure required invasive mechanical ventilation. All patients received trimethoprim-sulfamethoxazole and methylprednisolone treatment. Four patients recovered completely and one died. Conclusion Elderly (aged>55 years) IBD patients who are receiving immune-suppressive therapy or with decreased peripheral blood lymphocyte count are at higher risk of PJP.