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Therapeutic Advances in Infectious... 2024The presence of fungal infections has been described in patients after recovering from COVID-19. This study aims to conduct a systematic review of studies that reported... (Review)
Review
BACKGROUND AND AIMS
The presence of fungal infections has been described in patients after recovering from COVID-19. This study aims to conduct a systematic review of studies that reported fungal infections ( spp., , or spp.) in adults after recovering from COVID-19.
METHODS
We performed a systematic review through PubMed, Web of Science, OVID-Medline, Embase, and Scopus. The study selection process was performed independently and by at least two authors. We performed a risk of bias assessment using the Newcastle-Ottawa Scale for cohort and case-control studies, and the Joanna Briggs Institute's Checklists for Case Series and Case Reports.
RESULTS
The systematic search found 33 studies meeting all inclusion criteria. There was a total population of 774 participants, ranging from 21 to 87 years. From them, 746 developed a fungal infection. In 19 studies, spp. was reported as the main mycosis. In 10 studies, was reported as the main mycosis. In seven studies, spp. was reported as the main mycosis. Regarding the quality assessment, 12 studies were classified as low risk of bias and the remaining studies as high risk of bias.
CONCLUSION
Patients' clinical presentation and prognosis after recovering from COVID-19 with fungal infection differ from those reported patients with acute COVID-19 infection and those without COVID-19 infection.
PubMed: 38706456
DOI: 10.1177/20499361241242963 -
Mycopathologia May 2024To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number...
OBJECTIVES
To describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia.
METHODS
We examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics.
RESULTS
Among 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-β-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved.
CONCLUSION
Detection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.
Topics: Humans; Pneumonia, Pneumocystis; Male; High-Throughput Nucleotide Sequencing; Pneumocystis carinii; Female; Middle Aged; Aged; Adult; Aged, 80 and over; Respiratory System; Young Adult; Molecular Diagnostic Techniques
PubMed: 38704795
DOI: 10.1007/s11046-024-00849-y -
European Journal of Medical Research May 2024Pneumocystis pneumonia is an uncommon precipitant of acute respiratory distress syndrome and is associated with high mortality. Prone positioning ventilation has been... (Observational Study)
Observational Study
Prone positioning does not improve outcomes of intubated patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome: a single-center, retrospective, observational, cohort study.
BACKGROUND
Pneumocystis pneumonia is an uncommon precipitant of acute respiratory distress syndrome and is associated with high mortality. Prone positioning ventilation has been proven to reduce mortality in patients with moderate-severe acute respiratory distress syndrome. We investigated the effect of prone positioning on oxygenation and mortality in intubated patients with pneumocystis pneumonia comorbid with moderate-severe acute respiratory distress syndrome.
METHODS
In this single-center, retrospective, observational, cohort study, eligible patients were enrolled at West China Hospital of Sichuan University from January 1, 2017, to December 31, 2021. Data on demographics, clinical features, ventilation parameters, arterial blood gas, and outcomes were collected. Patients were assigned to the prone cohort or supine cohort according to whether they received prone positioning ventilation. The main outcome was 28-day mortality.
FINDINGS
A total of 79 patients were included in the study. Sixty-three patients were enrolled in the prone cohort, and 16 patients were enrolled in the supine cohort. The 28-day mortality was 61.9% in the prone cohort and 68.8% in the supine cohort (P = 0.26), and 90-day mortality was 66.7% in the prone cohort and 68.8% in the supine cohort (P = 0.55). Patients in the supine cohort had fewer invasive mechanical ventilation days and more ventilator-free days. The incidence of complications was higher in the prone cohort than in the supine cohort.
CONCLUSIONS
In patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome, prone positioning did not decrease 28-day or 90-day mortality. Trial registration ClinicalTrials.gov number, ChiCTR2200063889. Registered on 20 September 2022, https://www.chictr.org.cn/showproj.html?proj=174886 .
Topics: Humans; Male; Pneumonia, Pneumocystis; Female; Retrospective Studies; Prone Position; Respiratory Distress Syndrome; Middle Aged; Aged; Respiration, Artificial; Treatment Outcome; Adult; Patient Positioning; China
PubMed: 38698478
DOI: 10.1186/s40001-024-01868-7 -
Clinical Transplantation May 2024Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT) recipients. However, the risk factors associated with PJP in KT recipients remain debatable. Therefore, we conducted this meta-analysis to identify risk factors for PJP, which could potentially help to reduce PJP incidence and improve outcome of KT recipients.
METHODS
We systematically retrieved relevant studies in PubMed, EMBASE, and the Cochrane Library up to November 2023. Pooled odds ratios (ORs) or mean differences (MDs) and the corresponding 95% confidence intervals (CIs) were calculated to assess the impact of potential risk factors on the occurrence of PJP.
RESULTS
27 studies including 42383 KT recipients were included. In this meta-analysis, age at transplantation (MD = 3.48; 95% CI = .56-6.41; p = .02), cytomegalovirus (CMV) infection (OR = 4.00; 95% CI = 2.53-6.32; p = .001), BK viremia (OR = 3.38; 95% CI = 1.70-6.71; p = .001), acute rejection (OR = 3.66; 95% CI = 2.44-5.49; p = .001), ABO-incompatibility (OR = 2.51; 95% CI = 1.57-4.01; p = .001), estimated glomerular filtration rate (eGFR) (MD = -14.52; 95% CI = -25.37- (-3.67); p = .009), lymphocyte count (MD = -.54; 95% CI = -.92- (-.16); p = .006) and anti-PJP prophylaxis (OR = .53; 95% CI = .28-.98; p = .04) were significantly associated with PJP occurrence.
CONCLUSION
Our findings suggest that transplantation age greater than 50 years old, CMV infection, BK viremia, acute rejection, ABO-incompatibility, decreased eGFR and lymphopenia were risk factors for PJP.
Topics: Humans; Kidney Transplantation; Pneumonia, Pneumocystis; Risk Factors; Prognosis; Pneumocystis carinii; Postoperative Complications; Graft Rejection
PubMed: 38690617
DOI: 10.1111/ctr.15320 -
PLoS Genetics Apr 2024Pneumocystis jirovecii is a fungal pathogen that causes pneumocystis pneumonia, a disease that mainly affects immunocompromised individuals. This fungus has historically...
Pneumocystis jirovecii is a fungal pathogen that causes pneumocystis pneumonia, a disease that mainly affects immunocompromised individuals. This fungus has historically been hard to study because of our inability to grow it in vitro. One of the main drug targets in P. jirovecii is its dihydrofolate reductase (PjDHFR). Here, by using functional complementation of the baker's yeast ortholog, we show that PjDHFR can be inhibited by the antifolate methotrexate in a dose-dependent manner. Using deep mutational scanning of PjDHFR, we identify mutations conferring resistance to methotrexate. Thirty-one sites spanning the protein have at least one mutation that leads to resistance, for a total of 355 high-confidence resistance mutations. Most resistance-inducing mutations are found inside the active site, and many are structurally equivalent to mutations known to lead to resistance to different antifolates in other organisms. Some sites show specific resistance mutations, where only a single substitution confers resistance, whereas others are more permissive, as several substitutions at these sites confer resistance. Surprisingly, one of the permissive sites (F199) is without direct contact to either ligand or cofactor, suggesting that it acts through an allosteric mechanism. Modeling changes in binding energy between F199 mutants and drug shows that most mutations destabilize interactions between the protein and the drug. This evidence points towards a more important role of this position in resistance than previously estimated and highlights potential unknown allosteric mechanisms of resistance to antifolate in DHFRs. Our results offer unprecedented resources for the interpretation of mutation effects in the main drug target of an uncultivable fungal pathogen.
Topics: Tetrahydrofolate Dehydrogenase; Pneumocystis carinii; Folic Acid Antagonists; Drug Resistance, Fungal; Mutation; Methotrexate; Allosteric Regulation; Saccharomyces cerevisiae; Humans; Fungal Proteins; Catalytic Domain
PubMed: 38683847
DOI: 10.1371/journal.pgen.1011252 -
Infection and Drug Resistance 2024Lymphoma is complicated by intricate infections, notably pneumonia (PJP), marked by rapid progression, respiratory failure, and high mortality. Rapid diagnosis of PJP...
BACKGROUND
Lymphoma is complicated by intricate infections, notably pneumonia (PJP), marked by rapid progression, respiratory failure, and high mortality. Rapid diagnosis of PJP and effective administration of the first-line treatment trimethoprim-sulfamethoxazole (TMP-SMX) are important. For patients intolerant to TMP-SMX, selecting appropriate alternatives is challenging, necessitating careful decisions to optimize diagnosis and treatment. We present a lymphoma case complicated by PJP, illustrating medication adjustment until a positive response was observed.
CASE DESCRIPTION
A 41-year-old male patient with lymphoma presented with a week-long history of fever, fatigue, cough, sputum, chest tightness, and exertional dyspnea, unresponsive to treatment. Routine laboratory examinations revealed no pathogenic bacteria. PJ and (MTB) were detected in bronchoalveolar lavage fluid (BALF) using metagenomic next-generation sequencing (mNGS). On Day 1 of admission, meropenem, TMP-SMX, and rifampicin+isoniazid+levofloxacin were administered. However, the patient developed drug-induced hepatotoxicity and gastrointestinal adverse reactions after six days of treatment. After a multidisciplinary team discussion, anti-tuberculosis therapy was stopped because of insufficient evidence of tuberculosis infection. A reduced dose of TMP-SMX with micafungin was used for PJP; however, symptoms persisted and repeated computed tomography showed extensive deterioration of bilateral pulmonary plaques. The PJP regimen was modified to include a combination of TMP-SMX and caspofungin. Due to the high fever and elevated infection indices, the patient was treated with teicoplanin to enhance the anti-infection effects. By Day 13, the patient's temperature had normalized, and infection control was achieved by Day 30. CT revealed that the infection in both lung lobes fully resolved. Subsequently, lymphoma treatment commenced.
CONCLUSION
BALF-NGS facilitates early and rapid diagnosis of PJP. mNGS reads of MTB bacillus <5 may indicate a bacterial carrier state, warranting other detection techniques to support it. There is insufficient evidence for using TMP-SMX with micafungin to treat PJP; however, TMP-SMX combined with caspofungin is suitable.
PubMed: 38681899
DOI: 10.2147/IDR.S461607 -
Archives of Dermatological Research Apr 2024This study investigates the frequency of infections in autoimmune blistering disease (AIBD) patients treated with rituximab and evaluates the difference in infectious...
This study investigates the frequency of infections in autoimmune blistering disease (AIBD) patients treated with rituximab and evaluates the difference in infectious complications in patients on concomitant antibiotic and/or antiviral prophylaxis. The study retrospectively reviewed 43 AIBD patients who received rituximab over a five-year interval. The patients were categorized based on prophylaxis type (antibiotic, antiviral, or both) and concomitant immunosuppression status, which we defined as treatment with an immunosuppressive medication during the time frame they were given Rituximab. Our findings suggest that concomitant immunosuppression alongside rituximab did not significantly increase the risk of developing infectious complications compared to rituximab monotherapy. Results revealed that 34.4% of patients with concomitant immunosuppression had a secondary bacterial infection, defined as bacterial complications requiring hospitalization, consistent with prior studies. Moreover, antibiotic prophylaxis did not significantly reduce infection risk in patients on rituximab, with 45.1% of these patients experiencing bacterial complications. There was an absence of pneumocystis pneumonia in the study population. Despite the small sample size and limited timeline, this study suggests that antibiotic prophylaxis may not significantly mitigate the risk of infections in AIBD patients receiving rituximab, and the risk of infection with concomitant immunosuppression with rituximab requires additional investigation for definitive causal risk.
Topics: Humans; Rituximab; Retrospective Studies; Female; Male; Middle Aged; Aged; Autoimmune Diseases; Adult; Immunosuppressive Agents; Aged, 80 and over; Bacterial Infections; Antibiotic Prophylaxis; Anti-Bacterial Agents
PubMed: 38676739
DOI: 10.1007/s00403-024-02865-w -
Journal of Infection and Chemotherapy :... Apr 2024Nocardiosis in patients after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, but is associated with a significant mortality risk. Although...
Successful maintenance treatment of disseminated nocardiosis with cerebral abscess in a severely immunocompromised patient allergic to trimethoprim-sulfamethoxazole using moxifloxacin and high-dose minocycline: A case report.
Nocardiosis in patients after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, but is associated with a significant mortality risk. Although trimethoprim-sulfamethoxazole (TMP/SMX) remains the cornerstone of nocardiosis treatment, optimal alternative therapies for patients intolerant to TMP/SMX are not well-established. Herein, we report a case of disseminated nocardiosis with bacteremia and multiple lesions in the lungs and brain caused by Nocardia farcinica, in a 60-year-old man who had previously undergone allogeneic HSCT and was receiving immunosuppressants for severe chronic graft-versus-host disease. The patient received atovaquone for the prophylaxis of Pneumocystis pneumonia because of a previous serious allergic reaction to TMP/SMX. The patient was initially treated with imipenem/cilastatin and amikacin, which were later switched to ceftriaxone and amikacin based on the results of antimicrobial susceptibility testing. After switching to oral levofloxacin and a standard dose of minocycline, the patient experienced a single recurrence of brain abscesses. However, after switching to oral moxifloxacin and high-dose minocycline, the patient did not experience any relapses during the subsequent two years and seven months of treatment. In treating nocardiosis with brain abscesses, it is crucial to select oral antibiotics based on the antimicrobial susceptibility test results and pharmacokinetics, especially when TMP/SMX is contraindicated. A combination of oral moxifloxacin and high-dose minocycline could be a promising alternative therapy.
PubMed: 38670455
DOI: 10.1016/j.jiac.2024.04.008 -
Current Rheumatology Reports Apr 2024The purpose of this review is to summarize and evaluate most recent evidence on the epidemiology of infections and associated risk factors in patients with primary... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to summarize and evaluate most recent evidence on the epidemiology of infections and associated risk factors in patients with primary systemic vasculitides (PSV), as well as discuss mitigation strategies including the risk of antibiotic prophylaxis.
RECENT FINDINGS
Infections remain one of the leading causes of mortality in patients with PSV, with rates of severe infection ranging from 16 to 40% in different cohorts. Older age, frailty, renal and pulmonary involvement, and higher burden of comorbidities have been recognized as important patient-associated risk factors. Treatments including higher cumulative doses of glucocorticoids are associated with an increased risk of infections, and recent studies show the potential benefit of interventions such as reduced-dose glucocorticoid regimens. Existing mitigation strategies include screening, vaccination, and infection prophylaxis. The latter remains particularly important for Pneumocystis jirovecii pneumonia; however, the benefit-risk ratio seems to be less clear outside of induction phase (i.e., high dose of glucocorticoids) and optimal treatment duration remains less clear. Patients with PSV are at increased risk of infections, due to disease itself, comorbidities, and treatment side effects. Awareness of the timing and types of infection, as well as mitigation strategies are imperative to ensure treatment success and survival for patients.
PubMed: 38668813
DOI: 10.1007/s11926-024-01149-6 -
Journal of Fungi (Basel, Switzerland) Apr 2024pneumonia (PJP) has high mortality rates in immunocompromised children, even though routine prophylaxis has decreased in incidence. The aim of this case series is to...
BACKGROUND
pneumonia (PJP) has high mortality rates in immunocompromised children, even though routine prophylaxis has decreased in incidence. The aim of this case series is to present the radiological and clinical pathway of PJP in a pediatric population.
DESCRIPTION OF CASES
All PJP cases in non-HIV/AIDS patients diagnosed at Istituto Giannina Gaslini Pediatric Hospital in Genoa (Italy) from January 2012 until October 2022 were retrospectively evaluated. Nine cases were identified (median age: 8.3 years), and of these, 6/9 underwent prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX; five once-a-week schedules and one three times-a-week schedule), while 3/9 did not receive this. PJP was diagnosed by real-time PCR for -DNA in respiratory specimens in 7/9 cases and two consecutive positive detections of β-d-glucan (BDG) in the serum in 2/9 cases. Most patients (6/8) had a CT scan with features suggestive of PJP, while one patient did not undergo a scan. All patients were treated with TMP/SMX after a median time from symptoms onset of 3 days. In 7/9 cases, empirical TMP/SMX treatment was initiated after clinical suspicion and radiological evidence and later confirmed by microbiological data. Clinical improvement with the resolution of respiratory failure and 30-day survival included 100% of the study population.
DISCUSSION
Due to the difficulty in obtaining biopsy specimens, PJP diagnosis is usually considered probable in most cases. Moreover, the severity of the clinical presentation often leads physicians to start TMP/SMX treatment empirically. BDG proved to be a useful tool for diagnosis, and CT showed good accuracy in identifying typical patterns. In our center, single-day/week prophylaxis was ineffective in high-risk patients; the three-day/week schedule would, therefore, seem preferable and, in any case, should be started promptly in all patients who have an indication of pneumonia.
PubMed: 38667947
DOI: 10.3390/jof10040276