Multidrug-resistant Mycobacterium abscessus threatens patients with cystic fibrosis

2017 ◽  
Vol 5 (1) ◽  
pp. 15 ◽  
Author(s):  
Aaron van Dorn
Keyword(s):  
Cystic Fibrosis ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus

scholarly journals Mycobacterium abscessusCells Have Altered Antibiotic Tolerance and Surface Glycolipids in Artificial Cystic Fibrosis Sputum Medium

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Augusto Cesar Hunt-Serracin ◽  
Brian J. Parks ◽  
Joseph Boll ◽  
Cara C. Boutte
Keyword(s):  
Cystic Fibrosis ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Cell Physiology ◽  
Antibiotic Tolerance ◽  
Planktonic Cells ◽  
Content Type ◽  
Cystic Fibrosis Sputum ◽  
Poor Treatment ◽  
Nutrient Conditions

ABSTRACTMycobacterium abscessusis a biofilm-forming, multidrug-resistant nontuberculous mycobacterial (NTM) pathogen increasingly found in cystic fibrosis patients. Antibiotic treatment for these infections is often unsuccessful, partly due toM. abscessus’s high intrinsic antibiotic resistance. It is not clear whether antibiotic tolerance caused by biofilm formation also contributes to poor treatment outcomes. We studied the surface glycolipids and antibiotic tolerance ofM. abscessusbiofilms grown in artificial cystic fibrosis sputum (ACFS) medium to determine how they are affected by nutrient conditions that mimic infection. We found thatM. abscessusdisplays more of the virulence lipid trehalose dimycolate when grown in ACFS than when grown in standard lab medium. In ACFS medium, biofilm-associated cells were more antibiotic tolerant than planktonic cells in the same well. This contrasts with standard lab media, where both biofilm and planktonic cells are highly antibiotic tolerant. These results indicate thatM. abscessuscell physiology in biofilms depends on environmental factors and that nutrient conditions found within cystic fibrosis infections could contribute to both increased virulence and antibiotic tolerance.

scholarly journals Whole-Genome Sequences of Mycobacterium abscessus subsp. massiliense Isolates from Brazil

2021 ◽  
Vol 10 (28) ◽  
Author(s):  
Edson Machado ◽  
Fernanda Cristina Oliveira ◽  
Rafael Silva Duarte ◽  
Ana Carolina Carvalho ◽  
Pedro Henrique Campanini Cândido ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cystic Fibrosis Patient ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Whole Genome ◽  
Genome Sequences ◽  
Genome Composition ◽  
Content Type ◽  
Severe Infections

The Mycobacterium abscessus complex comprises multidrug-resistant, opportunistic, and rapidly growing pathogens responsible for severe infections. Here, we report the genome composition of four Mycobacterium abscessus subsp. massiliense isolates from three sources: two from the lung of a cystic fibrosis patient, one from a mammary cyst, and one from a gutter system.

scholarly journals Fatal Pulmonary Infection Due to Multidrug-Resistant Mycobacterium abscessus in a Patient with Cystic Fibrosis

2001 ◽  
Vol 39 (2) ◽  
pp. 816-819 ◽  
Author(s):  
M. Sanguinetti ◽  
F. Ardito ◽  
E. Fiscarelli ◽  
M. La Sorda ◽  
P. D'Argenio ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pulmonary Infection ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus

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)

scholarly journals Decontamination Strategies Used for AFB Culture Significantly Reduce the Viability of Mycobacterium abscessus Complex in Sputum Samples from Patients with Cystic Fibrosis

2021 ◽  
Vol 9 (8) ◽  
pp. 1597
Author(s):  
Dominic Stephenson ◽  
Audrey Perry ◽  
Andrew Nelson ◽  
Ali E. Robb ◽  
Matthew F. Thomas ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Oxalic Acid ◽  
Nontuberculous Mycobacteria ◽  
Optimal Recovery ◽  
Mycobacterium Abscessus ◽  
Colony Count ◽  
Respiratory Pathogens ◽  
Quantitative Culture ◽  
Mycobacterium Abscessus Complex ◽  
Oxalic Acids

Nontuberculous mycobacteria are important respiratory pathogens in patients with cystic fibrosis (CF). For diagnosis, international guidelines recommend culture of sputum that has been decontaminated via chemical treatment. Fifty-six sputum samples from 32 patients known to be previously colonized or infected with NTM were subdivided, and the aliquots were subjected to six different decontamination strategies, followed by quantitative culture for NTM. Thirty sputum samples contained Mycobacterium abscessus complex (MABSC) and 11 contained Mycobacterium avium complex (MAC). Decontamination strategies included treatment with N-acetyl L-cysteine with 2% sodium hydroxide (NALC-NaOH), 4% NaOH, 1% chlorhexidine, 0.5 N sulfuric acid, 5% oxalic acid, double decontamination with NALC-NaOH, followed by 5% oxalic acid, and saline (0.85%) as a control. The samples were also cultured directly with no treatment. Treatment with NALC-NaOH resulted in an average reduction in colony count of 87% for MABSC when compared with direct culture. NaOH at 4% caused a 98.3% average reduction in colony count. All treatments that included NaOH resulted in colony counts that were statistically lower than those obtained from direct culture or the saline-treated control (p < 0.05). Standard treatments using sulfuric or oxalic acids were less deleterious, but still resulted in an average reduction in colony count of at least 30%. The viability of MAC was much less affected by most decontamination treatments. In conclusion, the viability of MABSC was severely compromised by standard decontamination regimens. This supports recent evidence showing that optimal recovery of MABSC is achieved by culture on an appropriate selective agar without decontamination of sputum samples.

scholarly journals Comparing Mycobacterium massiliense and Mycobacterium abscessus lung infections in cystic fibrosis patients

2015 ◽  
Vol 14 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Anne-Laure Roux ◽  
Emilie Catherinot ◽  
Nathalie Soismier ◽  
Beate Heym ◽  
Gil Bellis ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Mycobacterium Abscessus ◽  
Mycobacterium Massiliense ◽  
Lung Infections

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 A Current Microbiological Picture of Mycobacterium Isolates from Istanbul, Turkey

2020 ◽  
Vol 69 (2) ◽  
pp. 185-191
Author(s):  
BILGE SUMBUL ◽  
MEHMET ZIYA DOYMAZ
Keyword(s):  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Diagnostic Methods ◽  
Current Status ◽  
Clinical Samples ◽  
Mycobacterium Fortuitum ◽  
Mycobacterium Species ◽  
Full Spectrum ◽  
Number Of Patients ◽  
Lowenstein Jensen

Despite advances in diagnosis and treatment, tuberculosis (TB) continues to be one of the essential health problems throughout the world. Turkey is considered to be endemic for TB. In this study, we analyzed the distribution of Mycobacterium species, compare the diagnostic methods, and susceptibilities to anti-tuberculosis drugs of TB isolates. The aim was to document the current status and to provide a frame of reference for future studies. In this study, 278 Mycobacterium species isolated from 7,480 patients between September 2015 and June 2019 were included. Löwenstein-Jensen medium (LJ) and MGIT 960 were used for the isolation of strains. Susceptibility to 1st-line anti-tuberculosis drugs was determined. Positivity rates in clinical samples were as follows: 1.4% for direct microscopic acid-fast bacilli (AFB) detection, 3.4% for growth on the LJ, and 3.7% for growth on MGIT-960. Two hundred thirty-three isolates were identified as Mycobacterium tuberculosis complex (MTBC) and 45 were non-tuberculous mycobacteria (NTMs). Eleven of the NTMs (24.4%) were Mycobacterium fortuitum group isolates, and eight NTMs (17.7%) were Mycobacterium abscessus complex isolates. A number of patients diagnosed with tuberculosis peaked twice between the ages of 20–31 and 60–71. A hundred and eighty-two MTBC isolates (78.1%) were susceptible to all 1st-line anti-tuberculosis drugs, while 51 isolates (21.9%) were resistant to at least one drug tested. The multidrug-resistant tuberculosis rate was 13.7% among resistant strains and 3% in all strains. The liquid cultures were better for detection of both MTBC and NTMs isolates. The data demonstrate that MTBC continues to be challenge for this country and indicates the need for continued surveillance and full-spectrum services of mycobacteriology laboratory and infectious diseases.

Environment in the lung of cystic fibrosis patients stimulates the expression of biofilm phenotype in Mycobacterium abscessus

2022 ◽  
Vol 71 (1) ◽  
Author(s):  
Bailey F. Keefe ◽  
Luiz E. Bermudez
Keyword(s):  
Cystic Fibrosis ◽  
Host Cell ◽  
Biofilm Formation ◽  
Type Species ◽  
Divalent Cations ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Link Type ◽  
Populations At Risk

Introduction. Pulmonary infections caused by organisms of the Mycobacterium abscessus complex are increasingly prevalent in populations at risk, such as patients with cystic fibrosis, bronchiectasis and emphysema. Hypothesis. M. abscessus infection of the lung is not observed in immunocompetent individuals, which raises the possibility that the compromised lung environment is a suitable niche for the pathogen to thrive in due to the overproduction of mucus and high amounts of host cell lysis. Aim. Evaluate the ability of M. abscessus to form biofilm and grow utilizing in vitro conditions as seen in immunocompromised lungs of patients. Methodology. We compared biofilm formation and protein composition in the presence and absence of synthetic cystic fibrosis medium (SCFM) and evaluated the bacterial growth when exposed to human DNA. Results. M. abscessus is capable of forming biofilm in SCFM. By eliminating single components found in the medium, it became clear that magnesium works as a signal for the biofilm formation, and chelation of the divalent cations resulted in the suppression of biofilm formation. Investigation of the specific proteins expressed in the presence of SCFM and in the presence of SCFM lacking magnesium revealed many different proteins between the conditions. M. abscessus also exhibited growth in SCFM and in the presence of host cell DNA, although the mechanism of DNA utilization remains unclear. Conclusions. In vitro conditions mimicking the airways of patients with cystic fibrosis appear to facilitate M. abscessus establishment of infection, and elimination of magnesium from the environment may affect the ability of the pathogen to establish infection.

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