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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 -
Medical Mycology Case Reports Jun 2024A 46-year-old diabetic woman with unilateral renal fungus ball was successfully treated with antifungal therapy, endoscopic extraction and ureteral stent placement. The...
A 46-year-old diabetic woman with unilateral renal fungus ball was successfully treated with antifungal therapy, endoscopic extraction and ureteral stent placement. The patient was initially treated for a right staghorn calculus, thereafter developed urinary symptoms. Imaging revealed distal left ureter filling defects and a previous stent at the ureteropelvic junction. Urine culture confirmed sensitive to Micafungin. Bilateral ureteroscopy facilitated the extraction of a left renal pelvis fungus ball. This case underscores the challenges in diagnosing fungal UTIs in patients with predisposing factors, and highlights a combined medical and surgical approach for effective treatment of renal fungus balls.
PubMed: 38681664
DOI: 10.1016/j.mmcr.2024.100649 -
IDCases 2024is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a...
is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a rare case of infection, isolated from a drainage fluid in a patient affected by lung cancer recovered in the University Hospital of Campania "Luigi Vanvitelli", Naples, Italy. The isolate was identified by phenotypic methods, i.e., Gram and Lactophenol cotton blue (LCB) staining, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. We identified on the third day from Sabouraud Dextrose Agar supplemented with chloramphenicol and gentamicin. Antifungal susceptibility test revealed that 5-fluorocytosine was the most active drug against , followed by itraconazole and voriconazole, micafungin, amphotericin B and fluconazole, posaconazole, anidulafungin, and caspofungin. Our data showed the importance of an early cultural and fast microbiology diagnosis based on the characteristic morphologic features observed in Gram-stained smears of blood culture positive bottles, and the validation via MALDI-TOF MS. This dual approach has significant impact in the clinical management of infectious diseases and antibiotic stewardship, by integrating sample processing, fluid handling, and detection for rapid bacterial diagnosis.
PubMed: 38681078
DOI: 10.1016/j.idcr.2024.e01959 -
Journal of Fungi (Basel, Switzerland) Apr 2024Vascular catheter-related infections, primarily caused by and , pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease...
Vascular catheter-related infections, primarily caused by and , pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease and considerable morbidity. We studied the efficacy of micafungin in systemic and lock therapies to eliminate catheter-based biofilms and deep tissue infections in experimental central venous catheter (CVC)-related candidemia in neutropenic rabbits. Silastic CVCs in rabbits were inoculated with 1 × 10 CFU/mL of or , establishing catheter-based biofilm, and subjected to various treatments. Neutropenic rabbits treated with a combination of lock therapy and systemic micafungin demonstrated the most significant reduction in fungal burden, from 5.0 × 10 to 1.8 × 10 CFU/mL of and from 5.9 × 10 to 2.7 × 10 CFU/mL of ( ≤ 0.001), in the CVC after 24 h, with full clearance of blood cultures after 72 h from treatment initiation. The combination of lock and systemic micafungin therapy achieved eradication of from all studied tissues (0.0 ± 0.0 log CFU/g) vs. untreated controls (liver 7.5 ± 0.22, spleen 8.3 ± 0.25, kidney 8.6 ± 0.07, cerebrum 6.3 ± 0.31, vena cava 6.6 ± 0.29, and CVC wash 2.3 ± 0.68 log CFU/g) ( ≤ 0.001). Rabbits treated with a combination of lock and systemic micafungin therapy demonstrated a ≥2 log reduction in in all treated tissues ( ≤ 0.05) except kidney. Serum (1→3)-β-D-glucan levels demonstrated significant decreases in response to treatment. The study demonstrates that combining systemic and lock therapies with micafungin effectively eradicates catheter-based biofilms and infections caused by or , particularly in persistently neutropenic conditions, offering promising implications for managing vascular catheter-related candidemia and providing clinical benefits in cases where catheter removal is not feasible.
PubMed: 38667964
DOI: 10.3390/jof10040293 -
Journal of Fungi (Basel, Switzerland) Mar 2024The species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially...
The species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations are opted for. However, resistance to antifungals has increased over the years. In view of this, nanoemulsions (NEs) may represent a nanotechnology strategy in the development of new therapeutic alternatives. Therefore, this study developed a co-encapsulated nanoemulsion with amphotericin B (AmB) and micafungin (MICA) (NEMA) for the control of infections caused by . NEs were developed in previous studies. Briefly, the NEs were composed of a mixture of 10% sunflower oil and cholesterol as the oil phase (5:1), 10% Polyoxyethylene (20) cetyl ether (Brij 58) and soy phosphatidylcholine as surfactant/co-surfactant (2:1), and 80% PBS as the aqueous phase. The in vivo assay used BALB/c mice weighing between 25 and 28 g that were immunosuppressed (CEUA/FCF/CAr n° 29/2021) and infected with CDC B11903. The in vivo results show the surprising potentiate of the antifungal activity of the co-encapsulated drugs in NE, preventing yeast from causing infection in the lung and thymus. Biochemical assays showed a higher concentration of liver and kidney enzymes under treatment with AmB and MICAmB. In conclusion, this combination of drugs to combat the infection caused by can be considered an efficient therapeutic option, and nanoemulsions contribute to therapeutic potentiate, proving to be a promising new alternative.
PubMed: 38667924
DOI: 10.3390/jof10040253 -
Frontiers in Pharmacology 2024Echinocandins, a prominent class of antifungals, are known for their broad-spectrum activity and favorable safety profiles. However, their bioavailability and efficacy...
Echinocandins, a prominent class of antifungals, are known for their broad-spectrum activity and favorable safety profiles. However, their bioavailability and efficacy via oral route are suboptimal. In this study, caspofungin and micafungin, the two most commonly used echinocandins, were evaluated in various environments simulating intestinal lumen. The results revealed that while both antifungals are effective in standard medium, their efficacy significantly diminishes in the presence of human small bowel aspirates and bovine bile. The study suggests that bowel contents and specifically bile acids may be a suppressive component, hindering the antifungal effects of echinocandins. This novel exploration sheds light on the poor oral bioavailability of echinocandins. The findings imply that echinocandins alone, regardless of administration route, may not be optimal for gastrointestinal (GI) fungal infections or invasive fungal infections originating from intestinal translocation. Further clinical investigations are warranted to validate and expand upon these observations.
PubMed: 38601473
DOI: 10.3389/fphar.2024.1376656 -
Journal of Community Hospital Internal... 2023Drug-induced urine discoloration, although usually benign, can still raise concern in healthcare facilities. This case report presents the second case of purple urine...
Drug-induced urine discoloration, although usually benign, can still raise concern in healthcare facilities. This case report presents the second case of purple urine discoloration associated with cefiderocol in a 64-year-old male admitted to the intensive care unit for ventilator-associated pneumonia. The patient required broad-spectrum antibiotic treatment with vancomycin, cefiderocol, amikacin, and micafungin. On the fourth day after initiating antibiotics, the presence of purplish urine in the foley bag was noted. Urinalysis showed 11-25 red blood cells/hpf, but cultures ruled out urinary tract infection. Further laboratory workup did not reveal any evidence of hemolysis or rhabdomyolysis. Cultures from the endotracheal aspirate grew multidrug-resistant Pseudomonas. Cefiderocol and amikacin were continued to complete a seven-day course. Two days after completion of the cefiderocol course, the urine discoloration cleared up, providing strong evidence that cefiderocol was the cause of the discoloration.
PubMed: 38596538
DOI: 10.55729/2000-9666.1256 -
Journal of Clinical and Experimental... 2024We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive...
We report the case of a 52-year-old male who presented to our hospital with cervical lymphadenopathy. Lymph node biopsy revealed small atypical lymphoid cells positive for CD3 and CD5 and negative for CD56 and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization. CD4-positive cells and CD8-positive cells were mixed in almost equal numbers. He was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). The patient received one cycle of chemotherapy, resulting in severe sepsis. While undergoing treatment in the intensive care unit with an antimicrobial agent and prednisone, ascitic fluid appeared. Abdominal aspiration revealed neutrophil-predominant ascites and microbiological studies revealed Candida albicans. However, ascites did not improve when treated with micafungin for Candida peritonitis. Abdominal aspiration was re-performed, and atypical lymphoid cells that were positive for CD3 and CD56 were detected. EBV-DNA levels in whole blood were significantly elevated. Atypical lymphoid cells were positive for EBER by in situ hybridization and Southern blot analysis showed EBV terminal repeat monoclonal patterns. Bone marrow examination revealed the same atypical lymphoid cells. Therefore, the patient was diagnosed with extranodal natural killer/T-cell lymphoma (ENKTL) with bone marrow involvement 3 months after the diagnosis of PTCL-NOS. Complications associated with PTCL-NOS and ENKTL are rare. PTCL-NOS, chemotherapy, sepsis, and prednisone might have led to immunodeficiency and reactivation of EBV, which might be one of the pathophysiologies for developing ENKTL. Our case indicates that measuring EBV-DNA in the blood is a simple and prompt examination to detect complications of EBV-associated lymphoma.
Topics: Male; Humans; Middle Aged; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lymphoma, T-Cell, Peripheral; Prednisone; Lymphoma, Extranodal NK-T-Cell; Ascites; Killer Cells, Natural; DNA
PubMed: 38538319
DOI: 10.3960/jslrt.23049 -
Pathogens (Basel, Switzerland) Mar 2024(1) Background: Despite being considered a non-pathogenic yeast, recently, a growing occurrence of infections has been noted. There is little knowledge about the drug...
(1) Background: Despite being considered a non-pathogenic yeast, recently, a growing occurrence of infections has been noted. There is little knowledge about the drug susceptibility of this species. Therefore, the objective of this research was to expand it and determine the drug susceptibility profile of a local collection of clinical isolates of this species. (2) Methods: This study contained 55 clinical isolates identified as using the MALDI-TOF method. The susceptibility of was tested to 10 antifungals (amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole, micafungin, anidulafungin, caspofungin, and itraconazole) using MICRONAUT-AT tests and manogepix, a new drug, using the microdilution method according to EUCAST. (3) Results: Overall, most strains were classified as sensitive to amphotericin B and flucytosine (MIC ranges of ≤0.03-1 and ≤0.06-0.125, respectively) and also to echinocandins. However, five isolates expressed high MIC values for all of the tested azoles, indicating cross-resistance. The MIC range for manogepix was 0.001-0.125 mg/L, with an MIC of 0.03 mg/L and an MIC of 0.06 mg/L. (4) Conclusions: The occurrence of resistance to azoles may be a concerning problem and therefore should be investigated further. However, the new antifungal manogepix appears to be an interesting new therapeutic option for treating such infections.
PubMed: 38535591
DOI: 10.3390/pathogens13030248 -
Journal of Fungi (Basel, Switzerland) Mar 2024Commercial tests are often employed in clinical microbiology laboratories for antifungal susceptibility testing of filamentous fungi. Method-dependent epidemiological... (Review)
Review
Commercial tests are often employed in clinical microbiology laboratories for antifungal susceptibility testing of filamentous fungi. Method-dependent epidemiological cutoff values (ECVs) have been defined in order to detect non-wild-type (NWT) isolates harboring resistance mechanisms. We reviewed the literature in order to find studies where commercial methods were used to evaluate for in vitro susceptibility of filamentous fungi and assess their ability to detect NWT isolates according to the available ECVs. Data were found for the gradient concentration strips Etest and MIC Test Strips (MTS), broth microdilution Sensititre YeastOne (SYO), Micronaut-AM and the agar dilution VIPcheck assays. Applying itraconazole, voriconazole and posaconazole Etest ECVs for , Etest was able to detect 90.3% (84/93), 61.2% (90/147) and 86% (31/36) of isolates with known mutations, respectively. Moreover, Etest also was able to detect 3/3 mutants using caspofungin ECVs and 2/3 micafungin mutant isolates. Applying the voriconazole and posaconazole SYO ECVs, 57.7% (67/116) and 100% (47/47) of mutants with known substitutions were classified as NWT, respectively. VIPcheck detected 90.3% (159/176), 80.1% (141/176) and 66% (141/176)of mutants via itraconazole, voriconazole and posaconazole, respectively, whereas Micronaut-AM detected 88% (22/25). In conclusion, Etest posaconazole and itraconazole, as well as micafungin and caspofungin ECVs, detected mutants. On the other hand, while the posaconazole SYO ECV was able to detect mutants, similar data were not observed with the SYO voriconazole ECV.
PubMed: 38535222
DOI: 10.3390/jof10030214