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Intensive Care Medicine Jun 2024Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic...
Pneumocystis pneumonia in intensive care: clinical spectrum, prophylaxis patterns, antibiotic treatment delay impact, and role of corticosteroids. A French multicentre prospective cohort study.
PURPOSE
Severe Pneumocystis jirovecii pneumonia (PJP) requiring intensive care has been the subject of few prospective studies. It is unclear whether delayed curative antibiotic therapy may impact survival in these severe forms of PJP. The impact of corticosteroid therapy combined with antibiotics is also unclear.
METHODS
This multicentre, prospective observational study involving 49 adult intensive care units (ICUs) in France was designed to evaluate the severity, the clinical spectrum, and outcomes of patients with severe PJP, and to assess the association between delayed curative antibiotic treatment and adjunctive corticosteroid therapy with mortality.
RESULTS
We included 158 patients with PJP from September 2020 to August 2022. Their main reason for admission was acute respiratory failure (n = 150, 94.9%). 12% of them received antibiotic prophylaxis for PJP before ICU admission. The ICU, hospital, and 6-month mortality were 31.6%, 35.4%, and 40.5%, respectively. Using time-to-event analysis with a propensity score-based inverse probability of treatment weighting, the initiation of curative antibiotic treatment after 96 h of ICU admission was associated with faster occurrence of death [time ratio: 6.75; 95% confidence interval (95% CI): 1.48-30.82; P = 0.014]. The use of corticosteroids for PJP was associated with faster occurrence of death (time ratio: 2.48; 95% CI 1.01-6.08; P = 0.048).
CONCLUSION
This study showed that few patients with PJP admitted to intensive care received prophylactic antibiotic therapy, that delay in curative antibiotic treatment was common and that both delay in curative antibiotic treatment and adjunctive corticosteroids for PJP were associated with accelerated mortality.
PubMed: 38829531
DOI: 10.1007/s00134-024-07489-2 -
BMJ Case Reports May 2024A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis...
A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis presented to hospital with worsening subacute shortness of breath. CT pulmonary angiogram demonstrated ground glass changes involving all lung lobes with an apicobasal gradient. These changes, combined with long-term steroid exposure for granulomatous hepatitis without pneumocystis prophylaxis, raised concern for pneumocystis jirovecii pneumonia (PJP). A subsequent bronchoscopic lavage specimen was positive on PCR for PJP and the patient was started on appropriate therapy. Clinical and radiological changes initially improved but after completion of therapy, symptoms and radiological abnormalities returned. Retreatment with second-line treatment resulted again in initial improvement followed by relapse with acute deterioration. Further investigations for an alternate diagnosis were made, with a surgical lung biopsy performed finally revealing immunosuppression-related Epstein-Barr virus positive large B cell lymphoma with lymphomatoid granulomatosis of grade 3 pattern.
Topics: Humans; Lymphomatoid Granulomatosis; Male; Diagnosis, Differential; Adult; Pneumonia, Pneumocystis; Pneumocystis carinii; Tomography, X-Ray Computed; Lung
PubMed: 38821563
DOI: 10.1136/bcr-2024-259969 -
Journal of Infection and Public Health Jul 2024Pneumocystis jirovecii pneumonia (PCP) is associated with significant mortality amongst patients without underlying human immunodeficiency virus infection (HIV). We...
Elevated serum lactate dehydrogenase aids prediction of mortality in Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection - Derivation of a clinical risk score.
Pneumocystis jirovecii pneumonia (PCP) is associated with significant mortality amongst patients without underlying human immunodeficiency virus infection (HIV). We sought to develop a risk score to predict mortality in this population. We reviewed patients with a presumed or confirmed PCP and a negative HIV test from 2006-2023. We constructed a multivariable model to identify parameters independently associated with mortality and the adjusted odds ratios were converted to weights to derive a risk score. Subsequently, we compared the performance of our score to the CURB-65 score by means of area under receiver operating characteristic curve (AUC). In total, we examined 93 patients with PCP without HIV. Mortality was 31.2%. Risk factors for mortality included older age, male sex and high serum lactate dehydrogenase levels (LDH) and C-reactive protein levels. A risk score was derived comprising age> 65 years (2 points), male sex (2 points) and LDH> 770 U/L (3 points). Our risk score (AUC 0.71, 95%CI 0.60-0.82) performed better than the CURB-65 score (AUC 0.53, 95%CI 0.41-0.66). A low-risk score of 0-1 had excellent negative predictive value for mortality (97.5%). In conclusion, a risk score comprising age, sex and LDH can predict mortality in PCP without underlying HIV and help with prognostication.
Topics: Humans; Male; Pneumonia, Pneumocystis; Female; L-Lactate Dehydrogenase; Middle Aged; Aged; Risk Factors; Pneumocystis carinii; ROC Curve; Adult; Retrospective Studies; Risk Assessment; HIV Infections; Aged, 80 and over
PubMed: 38820900
DOI: 10.1016/j.jiph.2024.04.023 -
World Journal of Clinical Cases May 2024The number of patients undergoing solid organ transplantation has increased annually. However, infections in solid organ transplant recipients can have a severe effect...
BACKGROUND
The number of patients undergoing solid organ transplantation has increased annually. However, infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants. Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4''-O-isovaleryltransferase gene (ist) from streptomyces thermotoleran. Carrimycin has good antibacterial and antiviral effects. However, no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia (SP) after solid organ transplantation.
AIM
To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment.
METHODS
In March 2022, ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022. When the condition was critical and difficult to control with other drugs, carrimycin was administered. These ten patients' clinical features and treatment protocols were retrospectively analyzed, and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated.
RESULTS
All ten patients were included in the analysis. Regarding etiological agent detection, there were three cases of fungal pneumonia, two cases of bacterial pneumonia, two cases of Pneumocystis pneumonia, and three cases of mixed infections. After treatment with carrimycin, the disease in seven patients significantly improved, the course of the disease was significantly shortened, fever was quickly controlled, chest computed tomography was significantly improved, and oxygenation was significantly improved. Finally, the patients were discharged after curing. One patient died of acute respiratory distress syndrome, and two patients discontinued treatment.
CONCLUSION
Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation. Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.
PubMed: 38817218
DOI: 10.12998/wjcc.v12.i15.2542 -
Frontiers in Microbiology 2024species are pathogenic fungi known to cause pneumonia in immunocompromised mammals. They are obligate to their host, replicate extracellularly in lung alveoli and...
INTRODUCTION
species are pathogenic fungi known to cause pneumonia in immunocompromised mammals. They are obligate to their host, replicate extracellularly in lung alveoli and thrive in the copper-enriched environment of mammalian lungs. In this study, we investigated the proteome of , a model organism that infects mice, in the context of its copper sensing and tolerance.
METHODS AND RESULTS
The query for copper-associated annotations in FungiDB followed by a manual curation identified only 21 genes in , significantly fewer compared to other clinically relevant fungal pathogens or phylogenetically similar free-living fungi. We then employed instrumental analyses, including Size-Exclusion Chromatography Inductively Coupled Plasma Mass Spectrometry (SEC-ICP-MS), Immobilized Metal Affinity Chromatography (IMAC), and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), to isolate and identify copper-binding proteins from freshly extracted organisms, revealing 29 distinct cuproproteins. The RNA sequencing (RNA-seq) analysis of exposed to various CuSO concentrations at three temporal intervals (0.5, 2, and 5 h) indicated that significant gene expression changes occurred only under the highest CuSO concentration probed (100 μM) and the longest exposure duration (5 h). This stimulus led to the upregulation of 43 genes and downregulation of 27 genes compared to untreated controls. Quantitative PCR (qPCR) confirmed the expression of four out of eight selected upregulated genes, including three assumed transcription factors (PNEG_01236, PNEG_01675, and PNEG_01730) and a putative copper transporter (PNEG_02609). Notably, the three applied methodologies - homology-based annotation, SEC-ICP-MS/IMAC/LC-MS/MS, and RNA-seq - yielded largely distinct findings, with only four genes (PNEG_02587, PNEG_03319, PNEG_02584, and PNEG_02989) identified by both instrumental methods.
DISCUSSION
The insights contribute to the broader knowledge of copper homeostasis and provide novel facets of host-pathogen interactions for extracellular pathogens. We suggest that future studies of pathogenicity and copper stress survival should consider the entire spectrum of identified genes.
PubMed: 38812685
DOI: 10.3389/fmicb.2024.1383737 -
Journal of Fungi (Basel, Switzerland) May 2024The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected...
The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected proportions, we have modelled the burden of fungal disease for the first time. The most prevalent serious fungal conditions are recurrent vulvovaginitis (~190,000 affected) and fungal asthma (~34,000 affected). Given the UAE's low prevalence of HIV, we estimate an at-risk population of 204 with respect to serious fungal infections with cryptococcal meningitis estimated at 2 cases annually, 15 cases of pneumonia (PCP) annually, and 20 cases of esophageal candidiasis in the HIV population. PCP incidence in non-HIV patients is estimated at 150 cases annually. Likewise, with the same low prevalence of tuberculosis in the country, we estimate a total chronic pulmonary aspergillosis prevalence of 1002 cases. The estimated annual incidence of invasive aspergillosis is 505 patients, based on local data on rates of malignancy, solid organ transplantation, and chronic obstructive pulmonary disease (5.9 per 100,000). Based on the 2022 annual report of the UAE's national surveillance database, candidaemia annual incidence is 1090 (11.8/100,000), of which 49.2% occurs in intensive care. Fungal diseases affect ~228,695 (2.46%) of the population in the UAE.
PubMed: 38786708
DOI: 10.3390/jof10050353 -
Pulmonary Therapy May 2024The presence of antibiotic allergy labels can have harmful impacts on clinical outcomes, particularly among immunosuppressed patients, in whom there have been...
INTRODUCTION
The presence of antibiotic allergy labels can have harmful impacts on clinical outcomes, particularly among immunosuppressed patients, in whom there have been associations with increased complications, readmission rates, and mortality. We explore the effects of a sulfonamide allergy label (SAL) on clinical outcomes in adult patients with Pneumocystis jirovecii pneumonia (PJP).
METHODS
In this retrospective matched cohort study, we utilized TriNetX, a multicenter national database, to match 535 adult patients with PJP and SAL to an equal number of controls. We identified cases indexed between 01/01/2010 and 01/01/2023 utilizing ICD-10 codes for PJP and allergy status to sulfonamides and through detection of P. jirovecii antigen with immunofluorescence or PCR. Propensity score matching was performed in a 1:1 fashion for demographics and comorbidities, and our analysis included clinical outcomes that occurred within 30 days after the occurrence of the index event.
RESULTS
While hospitalization risk tended to be lower among patients with SAL as compared to controls (RR: 0.90; 95% CI 0.81-1.01), there were no major differences in the risk of respiratory failure (RR: 0.94; 95% CI 0.84-1.05), prednisone use (RR: 1; 95% CI 0.91-1.10), intensive level of care requirement (RR: 0.85; 95% CI 0.69-1.06), intubation (RR: 0.85; 95% CI 0.61-1.19), or mortality (RR: 0.98; 95% CI 0.68-1.42). The presence of SAL did however impact antibiotic prescription patterns, with an underutilization of trimethoprim (RR: 0.50; 95% CI 0.43-0.59) and sulfamethoxazole (RR, 0.47; 95% CI 0.40-0.56) and overuse of alternative agents by patients with SAL as compared to controls. Yet, there was no difference in the occurrence of adverse outcomes such as hepatotoxicity (RR: 1.09; 95% CI 0.49-2.45) or acute kidney injury (RR: 0.94; 95% CI 0.78-1.14) between patients with SAL and controls.
CONCLUSIONS
The presence of SAL alters antibiotic prescription patterns among adults with Pneumocystis infection but has no clinically significant impact on outcomes.
PubMed: 38782820
DOI: 10.1007/s41030-024-00260-4 -
Annals of Intensive Care May 2024The recent epidemiology of Pneumocystis pneumonia (PCP) requiring intensive care unit (ICU) admission and the associated spectrum of immunocompromising conditions are...
PURPOSE
The recent epidemiology of Pneumocystis pneumonia (PCP) requiring intensive care unit (ICU) admission and the associated spectrum of immunocompromising conditions are poorly described.
METHODS
We analyzed all adult PCP cases admitted to French ICUs via the French medical database system (PMSI), over the period from 2013 to 2019.
RESULTS
French ICUs admitted a total of 4055 adult patients with PCP. Among all hospitalized PCP cases, the proportion requiring ICU admission increased from 17.8 in 2014 to 21.3% in 2019 (P < 0.001). The incidence of severe PCP rose from 0.85 in 2013 to 1.32/100,000 adult inhabitants in 2019 (P < 0.0001), primarily due to the proportion of HIV-negative patients that increased from 60.6% to 74.4% (P < 0.0001). Meanwhile, the annual number of severe PCP cases among patients with HIV infection remained stable over the years. In-hospital mortality of severe PCP cases was 28.5% in patients with HIV infection and 49.7% in patients without. Multivariable logistic analysis showed that patients with HIV infection had a lower adjusted risk of death than patients without HIV infection (Odds Ratio [OR]: 0.30, 95% confidence interval [95CI]: 0.17-0.55). Comorbidities or conditions strongly associated with hospital mortality included the patient's age, Simplified Acute Physiologic Score II, congestive heart failure, coagulopathy, solid organ cancer, and cirrhosis. A vast array of autoimmune inflammatory diseases affected 19.9% of HIV-negative patients.
CONCLUSIONS
The number of PCP cases requiring ICU admission in France has risen sharply. While the yearly count of severe PCP cases in HIV-infected patients has remained steady, this rise predominantly affects cancer patients, with a recent surge observed in patients with autoimmune inflammatory diseases, affecting one in five individuals.
PubMed: 38776012
DOI: 10.1186/s13613-024-01309-y -
Cureus Apr 2024A trio of spontaneous pneumomediastinum, pneumopericardium, and pneumothorax is a highly unusual presentation. The majority of reported cases are due to trauma, while...
A trio of spontaneous pneumomediastinum, pneumopericardium, and pneumothorax is a highly unusual presentation. The majority of reported cases are due to trauma, while the remaining cases are iatrogenic. Among infections, this trio has so far been reported in COVID-19 pneumonia and pneumocystis pneumonia in HIV-positive patients. There are case reports on pneumothorax and pneumomediastinum in tuberculosis, but the trio is not reported. Here, we present a case of a recently diagnosed HIV-positive patient with complaints of cough and shortness of breath whose initial workup was negative for Mycobacterium. The patient was, however, started on antitubercular drugs based on clinical radiological evidence. He developed spontaneous pneumothorax, pneumomediastinum, and pneumopericardium, and repeat bronchoalveolar lavage (BAL) came positive for Mycobacterium. The patient, however, could not be revived and succumbed to obstructive and septic shock.
PubMed: 38765397
DOI: 10.7759/cureus.58440 -
Transplantation Proceedings May 2024Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that, in immunocompromised patients, can progress to respiratory failure and death. Since...
Pneumocystis jirovecii Pneumonia in a Liver Transplant Recipient With an Adverse Reaction to Trimethoprim/Sulfamethoxazole Treated With a Sulfonamide Desensitization Protocol: Case Report.
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that, in immunocompromised patients, can progress to respiratory failure and death. Since trimethoprim/sulfamethoxazole (TMP/SMX) chemoprophylaxis has become a standard management, the prognosis has improved. However, there are patients with a history of TMP/SMX intolerance who cannot receive chemoprophylaxis.
BACKGROUND
We report on a 53-year-old male liver recipient treated with a standard triple immunosuppressive regimen in whom TMP/SMX was waived because of a history of allergy manifested as a generalized rash with edema more than 30 years ago. At transplantation, the immunologic risk was assessed as low, and liver graft function was normal. In the third month after engraftment, he developed dyspnea at rest required constant passive oxygen therapy. Ceftriaxone, azithromycin, and clindamycin were implemented. Mycophenolate acid was stopped, and tacrolimus was reduced. High-resolution computed tomography revealed interstitial pneumonia. Pneumocystis jirovecii pneumoniae was diagnosed from bronchoalveolar lavage. Instead of TMP/SMX, pentamidine and caspofungin were also used for PJP, with no improvement. After 3 weeks, the patient deteriorated. Because of his life-threatening condition, TMP/SMX was introduced in the sulfonamide desensitization protocol, including hydrocortisone and clemastinum. Within 4 days, the patient stabilized with no signs of TMP/SMX intolerance. Pneumonia subsided within a month, and TMP/SMX was prescribed lifelong.
CONCLUSIONS
Prophylaxis for PJP with TMP/SMX still remains an important issue in transplant recipients. Adverse reaction to TMP/SMX in the past is not always a contraindication to reintroducing prophylaxis. The decision of prophylaxis avoidance should be analyzed carefully; in uncertain cases, a sulfonamide desensitization protocol should be considered.
Topics: Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Liver Transplantation; Pneumocystis carinii; Sulfonamides; Desensitization, Immunologic; Immunocompromised Host; Immunosuppressive Agents
PubMed: 38760300
DOI: 10.1016/j.transproceed.2024.03.022