Relapsing bronchopneumonia due to community-associated methicillin-resistant Staphylococcus aureus: a case report.

BACKGROUND: The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased the incidence of community-onset MRSA infection. Respiratory tract infections caused by MRSA has been noted for their severity; however, repeated relapses that require extended antibiotic therapy are rare. CASE PRESENTATION: We report a case of relapsing bronchopneumonia caused by CA-MRSA in a 56-year-old man. The patient responded to antibiotics, but repeatedly relapsed after stopping treatment. MRSA was consistently isolated from airway specimens during each relapse. Extended oral antibiotic treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for 6 months achieved infection control. Whole-genome sequencing of the isolated strain revealed that the causative agent was sequence type (ST)1/staphylococcal cassette chromosome mec (SCCmec) type IVa, a clone that is rapidly increasing in Japan. DISCUSSION AND CONCLUSIONS: This patient had an unusual course of MRSA bronchopneumonia with repeated relapses. Although the choice of antibiotics for long-term use in MRSA respiratory tract infections has not been well established, TMP/SMX was effective and well tolerated for long-term therapy in this case. The clinical course of infections related to the rapid emerging clone, ST1/SCCmec type IVa warrants further attention.

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.

Reasons for implementation success despite health system constraints: qualitative insights on 'what worked' for cotrimoxazole preventive therapy.

BACKGROUND: Although Cotrimoxazole preventive therapy (CPT) has shown to be highly efficacious in reducing morbidity and mortality among people living with Human immunodeficiency virus (HIV) under 'ideal world' study conditions, operational challenges are limiting its effectiveness when implementing in countries most affected by the HIV epidemic. The fact that Mozambican authorities reported high coverage of CPT among patients with HIV, has led to this qualitative case study aimed at exploring possible factors responsible for the successful implementation of CPT in the Province of Maputo. METHODS: Between February and April 2019, we individually interviewed nine governmental stakeholders, including the person responsible for the HIV Program, the person responsible for the TB Program and the person responsible for Pharmaceutical management at three administrative levels (central, provincial and district level). Interviews were recorded, transcribed, and analysed thematically using MAXQDA Analytics Pro. Findings were translated from Portuguese into English. RESULTS: Five themes iteratively emerged: (a) Role of governance & leadership, (b) Pharmaceutical strategies, (c) Service delivery modifications, (d) Health care provider factors, and (e) Patients' perspectives. Interviews revealed that continuous supply of cotrimoxazole (CTZ) had been facilitated through multiple-source procurement and a push-pull strategy. One part of CTZ arrived in kits that were imported from overseas and distributed to public health facilities based on their number of outpatient consultations (push strategy). Another part of CTZ was locally produced and distributed as per health facility demand (pull strategy). Strong district level accountability also contributed to the public availability of CTZ. Interviewees praised models of differentiated care, the integrated HIV service delivery and drug delivery strategies for reducing long queues at the health facility, better accommodating patients' needs and reducing their financial and organisational burden. CONCLUSIONS: This study presents aspects that governmental experts believed to be key for the implementation of CPT in the Province of Maputo, Mozambique. Enhancing the implementation outcomes - drug availability and feasibility of the health facility-based service delivery - seemed crucial for the implementation progress. Reasons for the remarkable patient acceptability of CPT in our study setting should be further investigated.

Sulfamethoxazole-induced crystal nephropathy: characterization and prognosis in a case series.

Cotrimoxazole (Trimethoprim/Sulfamethoxazole-SMX) is frequently used in critically ill and immunocompromised patients. SMX is converted to N-acetyl-sulfamethoxazole (NASM) and excreted by the kidneys. NASM may form crystals in urine, especially in acid urine, that may induce a crystalline nephropathy. However, the imputability of crystals in acute kidney injury (AKI) has not been proven. We aimed to assess whether NASM crystals may promote AKI and to investigate risk factors associated with NASM crystalline nephropathy. Patients from Ile-de-France, France who developed AKI under SMX treatment introduced during hospitalization and had a crystalluria positive for NASM crystals were selected. Patients with excessive preanalytical delay for crystalluria or missing data regarding SMX treatment were excluded. We used the Naranjo score to assess the causal relationship between SMX and the development of AKI in patients with positive NASM crystalluria. Fourteen patients were included. SMX was the probable cause of AKI for 11 patients and a possible cause for 3 patients according to Naranjo score. Patients were exposed to high doses of SMX (but within recommended ranges), and most of them had a preexisting chronic kidney disease and were hypoalbuminemic. Urine pH was mildly acid (median 5.9). AKI occured more rapidly than expected after introduction of SMX (median 4 days) and recovered rapidly after drug discontinuation in most, but not all, cases. SMX is a probable cause of crystalline nephropathy. Monitoring of crystalluria in patients exposed to SMX may be of interest to prevent the development of crystalline nephropathy. Approval number of the study: BPD-2018-DIAG-008.

Antibiotics for UTI Prevention After Intradetrusor OnabotulinumtoxinA Injections.

IMPORTANCE: Urinary tract infections (UTIs) occur in 8.6% to 48.1% of patients after intradetrusor onabotulinumtoxinA injections. OBJECTIVE: The objective of this study was to evaluate both choice and duration of antibiotic prophylaxis on the incidence of UTI within 30 days after in-office onabotulinumtoxinA injections. STUDY DESIGN: We included a single-site, retrospective cohort of 305 patients with overactive bladder or bladder pain syndrome receiving postprocedure prophylactic antibiotics for in-office, 100-unit intradetrusor onabotulinumtoxinA injections from 2019 to 2023. Categories of antibiotic prophylaxis compared included (1) nitrofurantoin 100 mg twice daily for 3 days, (2) nitrofurantoin 100 mg twice daily for 5 days, (3) trimethoprim-sulfamethoxazole 160 mg/800 mg twice daily for 3 days, and (4) "other regimens." Primary outcome was incidence of UTI within 30 days. Variables were compared via χ2 test. Crude/adjusted odds were estimated using binary logistic regression. RESULTS: Incidence of UTI was 10.4% for 3-day nitrofurantoin, 20.5% for 5-day nitrofurantoin, 7.4% for 3-day trimethoprim-sulfamethoxazole, and 25.7% among "other regimens" (P = 0.023). Differences among primary regimens were substantial but not statistically significant: 3-day trimethoprim-sulfamethoxazole had 31% lower odds of UTI versus 3-day nitrofurantoin (odds ratio [OR], 0.689; P = 0.518). Compared with 3-day nitrofurantoin regimen, the 5-day nitrofurantoin regimen had twice the odds of UTI (OR, 2.22; P = 0.088). Those receiving "other regimens" had nearly 3 times the odds of UTI (OR, 2.98; P = 0.018). Results were similar adjusting for age and race. Overall urinary retention rate was 1.97%. CONCLUSIONS: Prophylactic antibiotic choice and duration of treatment potentially affect UTI incidence after in-office, intradetrusor onabotulinumtoxinA injections. Nitrofurantoin and trimethoprim-sulfamethoxazole for 3 days have the lowest UTI incidence.

Disseminated Nocardia nova in a child with relapsed acute lymphoblastic leukemia: a case report.

BACKGROUND: Nocardiosis is a rare infection that typically results from inhalation of or inoculation with Nocardia organisms. It may cause invasive disease in immunocompromised patients. This case describes nocardiosis with bacteremia and pulmonary involvement in a child with a hematologic malignancy. CASE PRESENTATION: A boy with testicular relapsed acute lymphoblastic leukemia with marrow involvement presented with sudden onset of fever, body aches, headaches, chills, and moderate respiratory distress during continuation 2 chemotherapy. Radiographic imaging demonstrated consolidation and ground glass opacities in bilateral lower lungs. Central line blood cultures grew Nocardia nova complex, prompting removal of the central line and initiation of triple therapy with imipenem-cilastatin, linezolid, and trimethoprim-sulfamethoxazole with rapid improvement of symptoms. Antibiotic susceptibilities showed a multidrug-susceptible isolate. The patient is anticipated to remain on trimethoprim-sulfamethoxazole for at least 12 months. CONCLUSIONS: In an immunocompromised child, blood cultures, chest imaging, and head imaging can aid in the diagnosis of disseminated nocardiosis. Long-term antibiotic therapy is necessary, guided by the organism and simplified with the results of antimicrobial susceptibility testing.

Acute Uncomplicated UTIs in Adults: Rapid Evidence Review.

An acute uncomplicated urinary tract infection (UTI) is a bacterial infection of the lower urinary tract with no sign of systemic illness or pyelonephritis in a noncatheterized, nonpregnant adult with no urologic abnormalities or immunocompromise. In women, a self-diagnosis of a UTI with the presence of typical symptoms (e.g., frequency, urgency, dysuria/burning sensation, nocturia, suprapubic pain), without vaginal discharge, is accurate enough to diagnose an uncomplicated UTI without further testing. Urine culture and susceptibility testing should be reserved for women with recurrent infection, treatment failure, history of resistant isolates, or atypical presentation to make a definitive diagnosis and guide antibiotic selection. First-line antibiotics include nitrofurantoin for five days, fosfomycin in a single dose, trimethoprim for three days, or trimethoprim/sulfamethoxazole for three days. Symptomatic treatment with nonsteroidal anti-inflammatory drugs and delayed antibiotics may be considered because the risk of complications is low. Increased fluids, intake of cranberry products, and methenamine hippurate can prevent recurrent infections. Antibiotic prophylaxis is also effective in preventing recurrence but has a risk of adverse effects and antimicrobial resistance. Men with lower UTI symptoms should always receive antibiotics, with urine culture and susceptibility results guiding the antibiotic choice. Clinicians should also consider the possibility of urethritis and prostatitis in men with UTI symptoms. First-line antibiotics for men with uncomplicated UTI include trimethoprim, trimethoprim/sulfamethoxazole, and nitrofurantoin for seven days. Uncomplicated UTIs in nonfrail women and men 65 years and older with no relevant comorbidities also necessitate a urine culture with susceptibility testing to adjust the antibiotic choice after initial empiric treatment; first-line antibiotics and treatment durations do not differ from those recommended for younger adults.

Clinical and immunological outcomes of HIV-exposed uninfected and HIV-unexposed uninfected children in the first 24 months of life in Western Kenya.

BACKGROUND: Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. METHODS: Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers living with HIV received combination antiretroviral therapy. Children who were HEU received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. RESULTS: Children who were HEU and children who were HUU had similar growth curves. Children who were HEU had lower rates of malaria (rate ratio 0.54, 95% CI 0.38, 0.77) and respiratory illness (rate ratio 0.80, 95% CI 0.68, 0.93). Trajectories of plasma cytokines and vaccine-specific antibodies were similar in children who were HEU and HUU. There were subtle differences in antimalarial antibody dynamics, in which children who were HEU had overall lower antibody levels against five of the 14 malaria antigens tested. CONCLUSIONS: Children who were HEU and born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to children who were HUU. Children who were HEU had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.

Estimating the impact of alternative programmatic cotrimoxazole strategies on mortality among children born to mothers with HIV: A modelling study.

BACKGROUND: World Health Organization (WHO) guidelines recommend cotrimoxazole prophylaxis for children who are HIV-exposed until infection is excluded and vertical transmission risk has ended. While cotrimoxazole has benefits for children with HIV, there is no mortality benefit for children who are HIV-exposed but uninfected, prompting a review of global guidelines. Here, we model the potential impact of alternative cotrimoxazole strategies on mortality in children who are HIV-exposed. METHODS AND FINDINGS: Using a deterministic compartmental model, we estimated mortality in children who are HIV-exposed from 6 weeks to 2 years of age in 4 high-burden countries: Côte d'Ivoire, Mozambique, Uganda, and Zimbabwe. Vertical transmission rates, testing rates, and antiretroviral therapy (ART) uptake were derived from UNAIDS data, trial evidence, and meta-analyses. We explored 6 programmatic strategies: maintaining current recommendations; shorter cotrimoxazole provision for 3, 6, 9, or 12 months; and starting cotrimoxazole only for children diagnosed with HIV. Modelled alternatives to the current strategy increased mortality to varying degrees; countries with high vertical transmission had the greatest mortality. Compared to current recommendations, starting cotrimoxazole only after a positive HIV test had the greatest predicted increase in mortality: Mozambique (961 excess annual deaths; excess mortality 339 per 100,000 HIV-exposed children; risk ratio (RR) 1.06), Uganda (491; 221; RR 1.04), Zimbabwe (352; 260; RR 1.05), and Côte d'Ivoire (125; 322; RR 1.06). Similar effects were observed for 3-, 6-, 9-, and 12-month strategies. Increased mortality persisted but was attenuated when modelling lower cotrimoxazole uptake, smaller mortality benefits, higher testing coverage, and lower vertical transmission rates. The study is limited by uncertain estimates of cotrimoxazole coverage in programmatic settings; an inability to model increases in mortality arising from antimicrobial resistance due to limited surveillance data in sub-Saharan Africa; and lack of a formal health economic analysis. CONCLUSIONS: Changing current guidelines from universal cotrimoxazole provision for children who are HIV-exposed increased predicted mortality across the 4 modelled high-burden countries, depending on test-to-treat cascade coverage and vertical transmission rates. These findings can help inform policymaker deliberations on cotrimoxazole strategies, recognising that the risks and benefits differ across settings.

Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin-piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. METHODS: We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin-piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin-piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713. FINDINGS: From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin-piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin-piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin-piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30-0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22-0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5-10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups. INTERPRETATION: Addition of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy. FUNDING: European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency.

Stenotrophomonas maltophilia Infections in Haematological Malignancies and Hematopoietic Stem Cell Transplantation: A Case Series including Cefiderocol-Based Regimens.

Background and Objectives: Stenotrophomonas maltophilia is a ubiquitous, aerobic, Gram-negative bacillus causing increasing concern in patients affected by haematological malignancies. Materials and Methods: We report a case series from two centres in Northern Italy to describe the characteristics, outcome and microbiological response of S. maltophilia infections in patients with haematological malignancies and/or allogenic hematopoietic stem cell transplantation (aHSCT). Results: Ten patients were included. The median age was 67 years, and seven patients (70%) were males. The median Charlson Comorbidity Index was 6 (IQR: 4-8). The most frequent haematological comorbidities were acute myeloid leukaemia (AML; n = 3; 30%) and non-Hodgkin's lymphoma (n = 3; 30%). Three (30%) patients underwent aHSCT before infection, all for AML. All the patients had undergone a recent antibiotics course and had an indwelling central venous catheter before infection. The main clinical presentations were nosocomial pneumonia, with (2; 20%) or without (4; 40%) secondary bloodstream infection and CRBSI (3; 30%). Four patients were treated with cefiderocol in monotherapy or combinations therapy with cotrimoxazole. The rest of the patients were treated with cotrimoxazole or levofloxacin in monotherapy. Conclusions: Despite a high rate of clinical improvement (90%) after starting antimicrobial therapy, we faced high 30-day mortality (30%) and in-hospital mortality (50%) rates in a highly comorbid population.

Disseminated nocardiosis with persistent neurological disease.

A man in his 80s with a history of sarcoidosis on chronic prednisone presented to the emergency department with several days of dyspnoea. A chest X-ray showed signs of pneumonia, and the patient was admitted. Blood and pleural fluid cultures grew Nocardia farcinica; therefore, the patient was started on treatment with trimethoprim-sulbactam and imipenem. Brain imaging showed evidence of dissemination of the infection to the central nervous system (CNS). The patient's admission was complicated by pleural effusions, acute kidney injury and pancytopenia, and therefore, his antibiotic regimen was ultimately transitioned from trimethoprim-sulfamethoxazole (TMP-SMX), meropenem and linezolid to imipenem and tedizolid. The patient received imipenem and tedizolid for the remainder of the admission. A repeat MRI of the brain was performed after 6 weeks of this dual antibiotic therapy, which unfortunately revealed persistent CNS disease. His regimen was then broadened to TMP-SMX, linezolid and imipenem. Despite these measures, however, the patient ultimately passed away from the infection.

Pneumocystis jirovecii pneumonia in people living with HIV: a review.

Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.

Comparison of Doxycycline or Minocycline to Sulfamethoxazole-Trimethoprim for Treatment of Stenotrophomonas maltophilia Pneumonia.

BACKGROUND: Stenotrophomonas maltophilia is a multidrug-resistant organism with limited antibiotic treatment options. Minocycline and doxycycline may be appropriate, but clinical data are limited. OBJECTIVE: To compare tetracyclines (minocycline and doxycycline [TCN]) with standard of care, sulfamethoxazole-trimethoprim (TMP-SMZ), in S. maltophilia pneumonia treatment. METHODS: This retrospective, 2-center study evaluated patients treated for S. maltophilia pneumonia with TCN or TMP-SMZ for clinical success, defined as resolution of leukocytosis, fever, and tachypnea. Patients were classified as treatment with TCN or TMP-SMZ based on definitive agent used for ≥50% of the treatment course and ≥4 days. Inclusion criteria were age ≥18 years, S. maltophilia confirmed on respiratory culture from January 2013 to November 2020, and appropriate definitive antibiotic dosing. Pregnancy, incarceration, S. maltophilia-resistant or intermediate to definitive therapy, and combination therapy for treatment of S. maltophilia pneumonia were exclusion criteria. Secondary outcomes were microbiologic success and recurrence or reinfection within 30 days requiring treatment. RESULTS: A total of 80 patients were included (21 TCN [15 minocycline, 6 doxycycline], 59 TMP-SMZ). There was no difference in clinical success (28.6% vs 25.4%; P = 0.994), microbiologic success (n = 28, 55.6% vs 66.4%; P = 0.677), or recurrence or reinfection (n = 24, 66.7% vs 26.7%; P = 0.092) between TCN and TMP-SMZ, respectively. CONCLUSION AND RELEVANCE: Clinical and microbiologic success rates were similar in patients treated with TCN compared with TMP-SMZ for S. maltophilia pneumonia. These data suggest minocycline and doxycycline may be options to treat S. maltophilia pneumonia, but conclusive clinical data continue to be lacking.

Actinomycetoma by Cellulosimicrobium cellulans in a Young Man from Guinea-Bissau: Short Literature Review Regarding a Case Report.

Mycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria. Cellulosimicrobium cellulans is a gram-positive bacterium from the order Actinomycetales that rarely causes human disease. The diagnosis is based on the clinical presentation and identification of the causative microorganism. We present a short literature review regarding the case report of a young man diagnosed with actinomycetoma due to Cellulosimicrobium cellulans and who received treatment with an association of amikacin and sulfamethoxazole/ trimethoprim (Welsh regimen).

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

BACKGROUND: Dihydropteroate 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. METHODS: Patients 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. RESULTS: A 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). CONCLUSIONS: In non-HIV-infected PCP, point mutants inside DHPS may not be associated with trimethoprim-sulfamethoxazole treatment outcomes. Further prospective large-scale studies are warranted.

Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis.

BACKGROUND: Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. OBJECTIVES: To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection. METHODS: A systematic review and individual patient data meta-analysis. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023. STUDY ELIGIBILITY CRITERIA: (a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis. PARTICIPANTS: SOT recipients. INTERVENTION: TMP-SMX prophylaxis versus no prophylaxis. ASSESSMENT OF RISK OF BIAS: Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies. METHODS OF DATA SYNTHESIS: For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100). CONCLUSIONS: In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.

Whipple’s disease-A typical endoscopic finding of a rare disease

A 49-year-old female presented with a 5-month course of diarrhoea, nocturn abdominal pain, asthenia, and weight loss of 30% of her body mass in three months. The patient had also a four-year medical history of bilateral mechanic gonalgy and arthralgias of the metacarpophalangeal and interphalangeal joints, despite treatment with prednisolone. On examination the patient had hyperpigmentation of the face and thorax, low-grade fever, and a BMI of 15,8 Kg/m2. Diarrhoea was documented with watery stools seven times per day despite loperamide, brownish, with no visible blood or mucous. Since the upper GI endoscopy and colonoscopy had no macroscopic abnormalities, the patient underwent a capsule endoscopy, which revealed continuous mucosal lesion with lymphangiectasia, oedema, villous atrophy and areas of denudation with hematinic punctate from the duodenum to the ileum. Diagnosis of Whipple’s Disease was made with typical histology findings in duodenum material and a positive PCR for Tropheryma whipplei. (AU)

Comparative genomics reveals the correlations of stress response genes and bacteriophages in developing antibiotic resistance of Staphylococcus saprophyticus.

IMPORTANCE: Staphylococcus saprophyticus is the second most common bacteria associated with urinary tract infections (UTIs) in women. The antimicrobial treatment regimen for uncomplicated UTI is normally nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), or a fluoroquinolone without routine susceptibility testing of S. saprophyticus recovered from urine specimens. However, TMP-SMX-resistant S. saprophyticus has been detected recently in UTI patients, as well as in our cohort. Herein, we investigated the understudied resistance patterns of this pathogenic species by linking genomic antibiotic resistance gene (ARG) content to susceptibility phenotypes. We describe ARG associations with known and novel SCCmec configurations as well as phage elements in S. saprophyticus, which may serve as intervention or diagnostic targets to limit resistance transmission. Our analyses yielded a comprehensive database of phenotypic data associated with the ARG sequence in clinical S. saprophyticus isolates, which will be crucial for resistance surveillance and prediction to enable precise diagnosis and effective treatment of S. saprophyticus UTIs.

Effect of co-trimoxazole and N-acetylcysteine alone and in combination on bacterial adherence on ureteral stent surface.

To assess the effect of co-trimoxazole and N-acetylcysteine (NAC), alone and in combination, on bacterial adherence to biofilm formed on ureteral stent surfaces. This prospective randomized study was conducted on 636 patients who underwent double J ureteral stent insertion after variable urological procedures. Patients were randomized into four groups: A (n = 165), no antibiotics or mucolytics during stent indwelling; B (n = 153), oral NAC (200 mg/day for children aged < 12 years old and 600 mg/day for adults) during stent indwelling; C (n = 162), oral co-trimoxazole (2 mg TMP/kg/day) during stent indwelling; and D (n = 156), both oral NAC and co-trimoxazole during stent indwelling. Two weeks following double J stent (JJ stent) insertion, urinalysis was performed on all patients and urine culture was done for all the patients at the day of double J stent removal. The stent was removed 2 weeks postoperatively, and a stent segment sized 3-5 cm from the bladder segment of the stent was sent for culture. Positive stent cultures were found in 63.6% (105/165), 43.1% (66/153), 37% (60/162), and 19.2% (30/156) patients of groups A, B, C, and D, respectively. E. coli was the organism most commonly isolated from the stent culture in all groups. The combination of co-trimoxazole and NAC was more effective in reducing bacterial adherence on ureteral stent surfaces than either alone.