Lung nodules due to Candida parapsilosis in a person with cystic fibrosis

2021 ◽  
Vol 14 (12) ◽  
pp. e245441
Author(s):  
Mary Bryson Piechowiak ◽  
Anne Whitney Brown ◽  
Shambhu Aryal ◽  
Shalika Basnayake Katugaha
Keyword(s):  
Cystic Fibrosis ◽  
Candida Parapsilosis ◽  
Opportunistic Infections ◽  
Pulmonary Nodules ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Lung Nodules ◽  
Intravenous Antibiotics ◽  
Progression Of Disease ◽  
Repeat Imaging

We present the first reported case of Candida parapsilosis pulmonary infection presenting as lung nodules. The patient is a 31-year-old man with cystic fibrosis (CF) colonised with multidrug-resistant Escherichia coli and increased frequency of pulmonary exacerbations in the preceding months. While on intravenous antibiotics for a pulmonary exacerbation, he developed bilateral pulmonary nodules. Bronchoalveolar lavage cultures grew C. parapsilosis. He was initially treated with dual antifungal therapy, voriconazole and micafungin. Discontinuation of voriconazole due to transaminitis resulted in the development of new nodules, and isavuconazonium was added. Repeat imaging revealed no progression of disease. Micafungin was eventually discontinued. Monotherapy with isavuconazonium is planned for 1 year post lung transplant. In the CF population, C. parapsilosis may be an opportunistic pathogen. The case highlights that frequent CF exacerbations and antibiotic exposure increase the risk for opportunistic infections including Candida species and the implications for lung transplantation in this setting.

scholarly journals Cystic Fibrosis andPseudomonas aeruginosa: the Host-Microbe Interface

2019 ◽  
Vol 32 (3) ◽  
Author(s):  
Sankalp Malhotra ◽  
Don Hayes ◽  
Daniel J. Wozniak
Keyword(s):  
Cystic Fibrosis ◽  
Pulmonary Disease ◽  
Virulence Factors ◽  
Opportunistic Pathogen ◽  
Innate Immune ◽  
Microbial Infection ◽  
Content Type ◽  
Adaptive Mutations ◽  
Ongoing Work ◽  
Progression Of Disease

SUMMARYIn human pathophysiology, the clash between microbial infection and host immunity contributes to multiple diseases. Cystic fibrosis (CF) is a classical example of this phenomenon, wherein a dysfunctional, hyperinflammatory immune response combined with chronic pulmonary infections wreak havoc upon the airway, leading to a disease course of substantial morbidity and shortened life span.Pseudomonas aeruginosais an opportunistic pathogen that commonly infects the CF lung, promoting an accelerated decline of pulmonary function. Importantly,P. aeruginosaexhibits significant resistance to innate immune effectors and to antibiotics, in part, by expressing specific virulence factors (e.g., antioxidants and exopolysaccharides) and by acquiring adaptive mutations during chronic infection. In an effort to review our current understanding of the host-pathogen interface driving CF pulmonary disease, we discuss (i) the progression of disease within the primitive CF lung, specifically focusing on the role of host versus bacterial factors; (ii) critical, neutrophil-derived innate immune effectors that are implicated in CF pulmonary disease, including reactive oxygen species (ROS) and antimicrobial peptides (e.g., LL-37); (iii)P. aeruginosavirulence factors and adaptive mutations that enable evasion of the host response; and (iv) ongoing work examining the distribution and colocalization of host and bacterial factors within distinct anatomical niches of the CF lung.

scholarly journals In Vitro Newly Isolated Environmental Phage Activity against Biofilms Preformed by Pseudomonas aeruginosa from Patients with Cystic Fibrosis

2021 ◽  
Vol 9 (3) ◽  
pp. 478
Author(s):  
Ersilia Vita Fiscarelli ◽  
Martina Rossitto ◽  
Paola Rosati ◽  
Nour Essa ◽  
Valentina Crocetta ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
In Vitro Test ◽  
Chronic Infections ◽  
Hospital Environments ◽  
Vitro Test ◽  
General Reliability ◽  
Phage Activity

As disease worsens in patients with cystic fibrosis (CF), Pseudomonas aeruginosa (PA) colonizes the lungs, causing pulmonary failure and mortality. Progressively, PA forms typical biofilms, and antibiotic treatments determine multidrug-resistant (MDR) PA strains. To advance new therapies against MDR PA, research has reappraised bacteriophages (phages), viruses naturally infecting bacteria. Because few in vitro studies have tested phages on CF PA biofilms, general reliability remains unclear. This study aimed to test in vitro newly isolated environmental phage activity against PA isolates from patients with CF at Bambino Gesù Children’s Hospital (OBG), Rome, Italy. After testing in vitro phage activities, we combined phages with amikacin, meropenem, and tobramycin against CF PA pre-formed biofilms. We also investigated new emerging morphotypes and bacterial regrowth. We obtained 22 newly isolated phages from various environments, including OBG. In about 94% of 32 CF PA isolates tested, these phages showed in vitro PA lysis. Despite poor efficacy against chronic CF PA, five selected-lytic-phages (Φ4_ZP1, Φ9_ZP2, Φ14_OBG, Φ17_OBG, and Φ19_OBG) showed wide host activity. The Φ4_ZP1-meropenem and Φ14_OBG-tobramycin combinations significantly reduced CF PA biofilms (p < 0.001). To advance potential combined phage-antibiotic therapy, we envisage further in vitro test combinations with newly isolated phages, including those from hospital environments, against CF PA biofilms from early and chronic infections.

scholarly journals 1458. Uncharted territories: applying “precision medicine” to understand the treacherous landscape of extensively and multidrug resistant (XDR and MDR) Pseudomonas aeruginosa in a patient with cystic fibrosis and lung transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S731-S731
Author(s):  
Laura J Rojas ◽  
Mohamad Yasmin ◽  
Jacquelynn Benjamino ◽  
Steven Marshall ◽  
Kailynn DeRonde ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Transplantation ◽  
Precision Medicine ◽  
Clinical Sample ◽  
Phylogenetic Reconstruction ◽  
Multidrug Resistant ◽  
Population Diversity ◽  
Before And After ◽  
Research Grant

Abstract Background Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with cystic fibrosis (CF). Herein, we describe our experience managing a young woman suffering from CF with XDR P. aeruginosa who underwent lung transplantation. We highlight the contemporary difficulties reconciling the clinical, microbiological, and genetic information. Methods Mechanism-based-susceptibility disk diffusion synergy testing with double and triple antibiotic combinations aided in choosing tailored antimicrobial combinations to control the infection in the pre-transplant period, create an effective perioperative prophylaxis regimen, and manage recurrent infections in the post-transplant period. Thirty-six sequential XDR and PDR P. aeruginosa isolates obtained from the patient within a 17-month period, before and after a double-lung transplant were analyzed by whole genome sequencing (WGS) and RNAseq in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time Results Our phylogenetic reconstruction demonstrates that these isolates represent a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggests that a group of closely related strains was present in the patient prior to transplantation and continued to evolve throughout the course of treatment regardless of antibiotic usage.Our findings challenge antimicrobial stewardship programs that assist with the selection and duration of antibiotic regimens in critically ill and immunocompromised patients based on single-isolate laboratory-derived resistant profiles. We propose that an approach sampling the population of pathogens present in a clinical sample instead of single colonies be applied instead when dealing with XDR P. aeruginosa, especially in patients with CF. Conclusion In complex cases such as this, real-time combination testing and genomic/transcriptomic data could lead to the application of true “precision medicine” by helping clinicians choose the combination antimicrobial therapy most likely to be successful against a population of MDR pathogens present. Disclosures Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)

Adult Xp11.2 translocation renal cell carcinoma managed effectively with pazopanib

2021 ◽  
Vol 14 (6) ◽  
pp. e243058
Author(s):  
Cristian Solano ◽  
Shrinjaya Thapa ◽  
Mohammad Muhsin Chisti
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Stable Disease ◽  
Renal Cell ◽  
Systemic Treatment ◽  
Pulmonary Nodules ◽  
Progression Of Disease ◽  
Xp11.2 Translocation ◽  
Adrenal Nodule

Xp11.2 translocation renal cell carcinoma (TRCC) is a rare and aggressive variant of renal cell carcinoma (RCC) when presenting in adults. We report a case of a man in his early 40s who was diagnosed with stage III Xp11.2 TRCC and underwent radical nephrectomy. Seven months following the surgery, an adrenal nodule and bilateral pulmonary nodules were discovered. He underwent cryoablation of the adrenal nodule and systemic treatment with daily pazopanib. He displayed stable disease for approximately 6 years. Following this period, multiple hospitalisations interrupted daily pazopanib therapy resulting in progression of disease. His regimen was then changed to ipilimumab and nivolumab, followed by current daily therapy with axitinib. The patient now shows stable disease in his 10th year after diagnosis. This case study demonstrates the efficacy of pazopanib for metastatic Xp11.2 TRCC and warrants further investigation to supplement the guidelines regarding the use of targeted therapy for TRCC.

scholarly journals Pulmonary Crohn's Disease in Down Syndrome: A Link or Linkage Problem

2016 ◽  
Vol 10 (2) ◽  
pp. 206-211
Author(s):  
Danyal Thaver ◽  
Mirza Beg
Keyword(s):  
Down Syndrome ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Pediatric Population ◽  
Pulmonary Nodules ◽  
Pulmonary Involvement ◽  
Lung Nodules ◽  
Inflammatory Disorder ◽  
Ct Guided ◽  
History Of

Crohn’s disease (CD) is an autoimmune inflammatory disorder that primarily affects the gastrointestinal tract. It may have pulmonary involvement, which has been rarely reported in pediatric patients. Down syndrome (DS) has been associated with increased frequency of autoimmune diseases. However, associations between CD and DS have been rarely reported. We present the case of a 5-year-old girl with known DS and a history of chronic intermittent abdominal pain who presented with persistent pneumonia. Her workup included a chest computed tomography (CT) scan that showed multiple noncalcified pulmonary nodules. An extensive infectious workup was done that was negative. CT-guided needle biopsy of the lung nodules showed necrotizing granulomas. This raised concern for primary CD with extraintestinal pulmonary manifestation. An esophagogastroduodenoscopy and colonoscopy were performed, and colon biopsies showed scattered epithelioid granulomas. Based on this information, there was consensus that her lung nodules were secondary to CD. She was started on standard therapy for CD, and her abdominal and respiratory symptoms gradually improved. However, she continues to have mild residual lung calcification and fibrosis. To our knowledge, this is the first reported case of pulmonary CD in a child with DS. The natural history of pulmonary CD in the pediatric population is not very well studied. Furthermore, since DS has been well known to be associated with increased frequency of malignancies and autoimmune conditions due to immune dysregulation, it is difficult to predict the severity and possible complications in this patient.

scholarly journals Pneumonia due to Pandoraea Apista after evacuation of traumatic intracranial hematomas:a case report and literature review

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chuanzhong Lin ◽  
Ning Luo ◽  
Qiang Xu ◽  
Jianjun Zhang ◽  
Mengting Cai ◽  
...  
Keyword(s):  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Multi Drug Resistance ◽  
Emerging Pathogen ◽  
Case Presentation ◽  
Ionization Time ◽  
Flight Mass Spectrometry ◽  
Antibiotic Susceptibility Test ◽  
Chinese Physicians ◽  
Level Identification

Abstract Background Pandoraea species is a newly described genus, which is multidrug resistant and difficult to identify. Clinical isolates are mostly cultured from cystic fibrosis (CF) patients. CF is a rare disease in China, which makes Pandoraea a total stranger to Chinese physicians. Pandoraea genus is reported as an emerging pathogen in CF patients in most cases. However, there are few pieces of evidence that confirm Pandoraea can be more virulent in non-CF patients. The pathogenicity of Pandoraea genus is poorly understood, as well as its treatment. The incidence of Pandoraea induced infection in non-CF patients may be underestimated and it’s important to identify and understand these organisms. Case presentation We report a 44-years-old man who suffered from pneumonia and died eventually. Before his condition deteriorated, a Gram-negative bacilli was cultured from his sputum and identified as Pandoraea Apista by matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS). Conclusion Pandoraea spp. is an emerging opportunistic pathogen. The incidences of Pandoraea related infection in non-CF patients may be underestimated due to the difficulty of identification. All strains of Pandoraea show multi-drug resistance and highly variable susceptibility. To better treatment, species-level identification and antibiotic susceptibility test are necessary.

scholarly journals In Vitro Activities of Designed Antimicrobial Peptides against Multidrug-Resistant Cystic Fibrosis Pathogens

1999 ◽  
Vol 43 (6) ◽  
pp. 1435-1440 ◽  
Author(s):  
Ute Schwab ◽  
Peter Gilligan ◽  
Jesse Jaynes ◽  
David Henke
Keyword(s):  
Cystic Fibrosis ◽  
Antimicrobial Peptides ◽  
Burkholderia Cepacia ◽  
Wide Spectrum ◽  
Multidrug Resistant ◽  
Medium Composition ◽  
Peptide Antibiotics ◽  
Rpmi Medium ◽  
Multidrug Resistant Pathogens

ABSTRACT The emergence of multidrug-resistant pathogens renders antibiotics ineffective in the treatment of lung infections in patients with cystic fibrosis (CF). Designed antimicrobial peptides (DAPs) are laboratory-synthesized peptide antibiotics that demonstrate a wide spectrum of antibacterial activity. Optimal conditions for susceptibility testing of these peptides have not yet been established. Medium composition is clearly a major factor influencing the results and reproducibilities of susceptibility tests. Using time-kill assays, we tested the effects of different media and buffers on the bactericidal activities of the peptides D2A21 and D4E1 onStaphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 27853. Each peptide at 1 and 5 μM was incubated with bacteria in the different media and buffers. Both peptides were most active in Tris-HCl buffer against S. aureus andP. aeruginosa. Among the more complex media tested, modified RPMI medium was the medium in which the peptides demonstrated the highest activity, while it supported the growth of the bacteria. The broth microdilution technique was used to test the activities of D2A21 and D4E1 in modified RPMI medium against multidrug-resistant pathogens from patients with CF. The MICs of DAPs for methicillin-resistant S. aureus ranged from 0.25 to 4 μg/ml, those for multidrug-resistant P. aeruginosa ranged from 0.125 to 4 μg/ml, those for Stenotrophomonas maltophilia ranged from 0.5 to 32 μg/ml, and those forBurkholderia cepacia ranged from 32 to ≥64 μg/ml. When the activity of peptide D2A21 was compared with that of the tracheal antimicrobial peptide (TAP), D2A21 had greater potency than TAP againstP. aeruginosa. In addition, no difference in the MICs of D2A21 was seen when it was tested in nutrient broth supplemented with NaCl at different concentrations. Thus, DAPs are a class of salt-insensitive antibiotics potentially useful in the treatment of CF patients harboring multidrug-resistant P. aeruginosa.

scholarly journals F-type Pyocins are Diverse Non-Contractile Phage Tail-Like Weapons for Killing Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Senjuti Saha ◽  
Chidozie D. Ojobor ◽  
Erik Mackinnon ◽  
Olesia I. North ◽  
Joseph Bondy-Denomy ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bactericidal Activity ◽  
Pathogenic Bacteria ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Antibiotic Resistant ◽  
Genes Encoding ◽  
Intraspecies Competition

ABSTRACTMost Pseudomonas aeruginosa strains produce bacteriocins derived from contractile or non-contractile phage tails known as R-type and F-type pyocins, respectively. These bacteriocins possess strain-specific bactericidal activity against P. aeruginosa and likely increase evolutionary fitness through intraspecies competition. R-type pyocins have been studied extensively and show promise as alternatives to antibiotics. Although they have similar therapeutic potential, experimental studies on F-type pyocins are limited. Here, we provide a bioinformatic and experimental investigation of F-type pyocins. We introduce a systematic naming scheme for genes found in R- and F-type pyocin operons and identify 15 genes invariably found in strains producing F-type pyocins. Five proteins encoded at the 3’-end of the F-type pyocin cluster are divergent in sequence, and likely determine bactericidal specificity. We use sequence similarities among these proteins to define 11 distinct F-type pyocin groups, five of which had not been previously described. The five genes encoding the variable proteins associate in two modules that have clearly re-assorted independently during the evolution of these operons. These proteins are considerably more diverse than the specificity-determining tail fibers of R-type pyocins, suggesting that F-type pyocins emerged earlier or have been subject to distinct evolutionary pressures. Experimental studies on six F-type pyocin groups show that each displays a distinct spectrum of bactericidal activity. This activity is strongly influenced by the lipopolysaccharide O-antigen type, but other factors also play a role. F-type pyocins appear to kill as efficiently as R-type pyocins. These studies set the stage for the development of F-type pyocins as anti-bacterial therapeutics.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen that causes a broad spectrum of antibiotic resistant infections with high mortality rates, particularly in immunocompromised individuals and cystic fibrosis patients. Due to the increasing frequency of multidrug-resistant P. aeruginosa infections, there is great interest in the development of alternative therapeutics. One alternative is protein-based antimicrobials called bacteriocins, which are produced by one strain of bacteria to kill other strains. In this study, we investigate F-type pyocins, bacteriocins naturally produced by P. aeruginosa that resemble non-contractile phage tails. We show that they are potent killers of P. aeruginosa, and distinct pyocin groups display different killing specificities. We have identified the probable specificity determinants of F-type pyocins, which opens up the potential to engineer them to precisely target strains of pathogenic bacteria. The resemblance of F-type pyocins to well characterized phage tails will greatly facilitate their development into effective antibacterials.

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