scholarly journals A Murine Model of Mycobacterium kansasii Infection Reproducing Necrotic Lung Pathology Reveals Considerable Heterogeneity in Virulence of Clinical Isolates

2021 ◽  
Vol 12 ◽  
Author(s):  
Vinicius O. Mussi ◽  
Thatiana L. B. V. Simão ◽  
Fabrício M. Almeida ◽  
Edson Machado ◽  
Luciana D. de Carvalho ◽  
...  
Keyword(s):  
Lung Disease ◽  
Pulmonary Disease ◽  
Virulent Strain ◽  
The United States ◽  
Clinical Isolates ◽  
Lung Pathology ◽  
Mycobacterium Kansasii ◽  
Considerable Heterogeneity ◽  
Highly Virulent

Among non-tuberculous mycobacteria, Mycobacterium kansasii is one of the most pathogenic, able to cause pulmonary disease indistinguishable from tuberculosis in immunocompetent susceptible adults. The lack of animal models that reproduce human-like lung disease, associated with the necrotic lung pathology, impairs studies of M. kansasii virulence and pathogenicity. In this study, we examined the ability of the C57BL/6 mice, intratracheally infected with highly virulent M. kansasii strains, to produce a chronic infection and necrotic lung pathology. As a first approach, we evaluated ten M. kansasii strains isolated from Brazilian patients with pulmonary disease and the reference strain M. kansasii ATCC 12478 for virulence-associated features in macrophages infected in vitro; five of these strains differing in virulence were selected for in vivo analysis. Highly virulent isolates induced progressive lung disease in mice, forming large encapsulated caseous granulomas in later stages (120–150 days post-infection), while the low-virulent strain was cleared from the lungs by day 40. Two strains demonstrated increased virulence, causing premature death in the infected animals. These data demonstrate that C57BL/6 mice are an excellent candidate to investigate the virulence of M. kansasii isolates. We observed considerable heterogeneity in the virulence profile of these strains, in which the presence of highly virulent strains allowed us to establish a clinically relevant animal model. Comparing public genomic data between Brazilian isolates and isolates from other geographic regions worldwide demonstrated that at least some of the highly pathogenic strains isolated in Brazil display remarkable genomic similarities with the ATCC strain 12478 isolated in the United States 70 years ago (less than 100 SNPs of difference), as well as with some recent European clinical isolates. These data suggest that few pathogenic clones have been widely spread within M. kansasii population around the world.

scholarly journals In Vitro Activity of Doripenem, a Carbapenem for the Treatment of Challenging Infections Caused by Gram-Negative Bacteria, against Recent Clinical Isolates from the United States

2008 ◽  
Vol 52 (12) ◽  
pp. 4388-4399 ◽  
Author(s):  
Chris M. Pillar ◽  
Mohana K. Torres ◽  
Nina P. Brown ◽  
Dineshchandra Shah ◽  
Daniel F. Sahm
Keyword(s):  
The United States ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
Ventilator Associated Pneumonia ◽  
Coagulase Negative Staphylococci ◽  
Hospital Acquired Pneumonia ◽  
Abdominal Infections ◽  
Hospital Acquired ◽  
Gram Positive Cocci

ABSTRACT Doripenem, a 1β-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (μg/ml) were established by broth microdilution. By MIC90, doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, ≤0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC90 of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum β-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC90/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC90 = 2, 89.1%S) was twice as active by MIC90 as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including β-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of β-lactam resistance.

scholarly journals 1593. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against OXA-48 β-lactamase–Producing Enterobacterales Collected in International Medical Centers, Including the United States, in 2017–2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S793-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang
Keyword(s):  
Antimicrobial Agents ◽  
The United States ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Multiple Resistance ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Custom Made

Abstract Background OXA-48 is a carbapenemase with low-level hydrolytic activity toward cephalosporins. This study evaluated in vitro activities of ceftazidime-avibactam (CAZ-AVI), meropenem (MEM), meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T), and other antimicrobial agents against 113 OXA-48-producing Enterobacterales with multiple resistance mechanisms collected in a 2017–2018 global surveillance program. Methods Nonduplicate clinical isolates of 113 Enterobacterales were collected from medical centers in 25 countries in 2017–2018. In vitro susceptibility tests were performed by broth microdilution with a custom-made panel consisting of CAZ-AVI, ceftazidime (CAZ), MEM, MVB, C/T, colistin (COL), gentamicin (GEN), levofloxacin (LEV), and amikacin (AMK). Whole genome sequencing or quantitative PCR data were used to analyze resistance mechanisms, such as OXA-48, extended-spectrum β-lactamase (ESBL), original-spectrum β-lactamase (OSBL), and AmpC β-lactamase. Clinical and Laboratory Standards Institute breakpoints were applied for susceptibility interpretations. Results Of 113 OXA-48–producing clinical isolates, 20 carried OXA-48 alone. The remaining 93 isolates carried additional β-lactamases, including 63 with ESBL (CTX-M-15) + OSBL (SHV, TEM), 15 with AmpC (DHA, AAC, CMY) + ESBL (CTX-M-15), and 15 with OSBL (SHV, TEM). 99.1% (all but 1) of all isolates tested were susceptible to CAZ-AVI, whereas 71.7%, 17.7%, and 14.2% were susceptible to MVB, MEM, and C/T, respectively. Among isolates harboring multiple resistance mechanisms (OXA-48 + ESBL + OSBL; n=63), 98.4%, 69.8%, 11.1%, and 7.9% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively. Among isolates carrying OXA-48 + AmpC + ESBL + OSBL (n=15), 100%, 66.7%, 13.3%, and 13.3% were susceptible to CAZ-AVI, MVB, MEM, and C/T, respectively (Table). Aminoglycosides (AMK and GEN) and other β-lactams (eg, CAZ) were 20%–90% active against these isolates. COL was the second most effective comparator, inhibiting 83.2% of these isolates. Table Conclusion CAZ-AVI was the most effective agent in this study compared with other antibiotics, including β-lactams, β-lactam–β-lactamase inhibitor combinations, aminoglycosides, and COL, against OXA-48-producing Enterobacterales carrying multiple β-lactamases. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee)

scholarly journals In vitro susceptibility studies and detection of vancomycin resistance genes in clinical isolates of enterococci in Nagasaki, Japan

1997 ◽  
Vol 119 (2) ◽  
pp. 175-181 ◽  
Author(s):  
Y. HIRAKATA ◽  
T. YAMAGUCHI ◽  
K. IZUMIKAWA ◽  
J. MATSUDA ◽  
K. TOMONO ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Antimicrobial Agents ◽  
The United States ◽  
Vancomycin Resistance ◽  
Single Step ◽  
Clinical Isolates ◽  
Glycopeptide Resistance ◽  
In Vitro Susceptibility ◽  
Enterococcus Gallinarum

Glycopeptide resistance in enterococci is now a cause of clinical concern in the United States and Europe. However, details of vancomycin resistance in enterococci in Japan have been unknown. We measured minimum inhibitory concentrations (MICs) of various antimicrobial agents for a total of 218 clinical strains of enterococci isolated in our hospital in 1995–6 in addition to 15 strains with known genotypic markers of resistance. We also screened vancomycin resistance genes using a single step multiplex-PCR.In clinical isolates, only two strains of Enterococcus gallinarum were of intermediate resistance to vancomycin (MIC, 8 μg/ml), while the others were all susceptible. Glycopeptides (vancomycin and teicoplanin) and streptogramins (RP 58500 and RPR 106972) showed potent antimicrobial effects for the isolates. In addition, ampicillin was also potent for Enterococcus faecalis, while ampicillin, minocycline and gentamicin were potent for Enterococcus avium. No vanA or vanB genes were detected, while vanC1 and vanC23 genes were detected from two and four strains, respectively. Our results suggest that incidence of VRE in Japan may be estimated as still very low at this time.

scholarly journals Characterization of the pathogenesis and immune response to Listeria monocytogenes strains isolated from a sustained national outbreak

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pallab Ghosh ◽  
Yan Zhou ◽  
Quentin Richardson ◽  
Darren E. Higgins
Keyword(s):  
Listeria Monocytogenes ◽  
Laboratory Strain ◽  
The United States ◽  
Clinical Isolates ◽  
T Cell Antigens ◽  
Life Threatening ◽  
Cellular Immune ◽  
The Brain

AbstractListeria monocytogenes is an intracellular pathogen responsible for listeriosis, a foodborne disease that can lead to life-threatening meningitis. The 2011 L. monocytogenes cantaloupe outbreak was among the deadliest foodborne outbreaks in the United States. We conducted in vitro and in vivo infection analyses to determine whether strains LS741 and LS743, two clinical isolates from the cantaloupe outbreak, differ significantly from the common laboratory strain 10403S. We showed that LS741 and LS743 exhibited increased virulence, characterized by higher colonization of the brain and other organs in mice. Assessment of cellular immune responses to known CD8+ T cell antigens was comparable between all strains. However, pre-existing immunity to 10403S did not confer protection in the brain against challenge with LS741. These studies provide insights into the pathogenesis of clinical isolates linked to the 2011 cantaloupe outbreak and also indicate that currently utilized laboratory strains are imperfect models for studying L. monocytogenes pathogenesis.

In vitro and in vivo interactions between Erwinia amylovora and related saprophytic bacteria

1975 ◽  
Vol 21 (1) ◽  
pp. 35-41 ◽  
Author(s):  
J. M. Erskine ◽  
L. E. Lopatecki
Keyword(s):  
Erwinia Amylovora ◽  
Virulent Strain ◽  
Sucrose Concentration ◽  
Sugar Content ◽  
Susceptible Host ◽  
The Status ◽  
Highly Virulent ◽  
Host Tissues

Under carefully controlled laboratory conditions, a highly virulent strain of Erwinia amylovora coinhabited susceptible host tissues with a yellow saprophytic bacterium, which was invariably isolated from fire blight infected trees, with or without producing symptoms of the disease depending on the status of a number of environmental factors, both climatic and physiological. In particular, variation of temperature and sucrose concentration determined, independently, the equilibrium of a readily reversible alternation of predominance of the two bacteria.It is suggested that E. amylovora may sometimes exist as an avirulent resident on the surface or within healthy host plants when environmental conditions favor growth of the yellow saprophyte rather than the pathogen. Such conditions, which are more likely to be obtained in midsummer and the fall, include temperature fall or rise below or above the optimum for E. amylovora, decreased humidity or diminution of sap flow, and increased sugar content in the host tissues.

scholarly journals Identification of virulence tal gene in the cotton pathogen, Xanthomonas citri pv. malvacearum strain Xss-V2-18

2020 ◽  
Author(s):  
Fazal Haq ◽  
Syed Mashab Ali Shah ◽  
Shiwang Xie ◽  
Kunxuan Huang ◽  
Wenxiu Ma ◽  
...  
Keyword(s):  
Virulent Strain ◽  
Evolutionary Relationship ◽  
The United States ◽  
In Planta ◽  
Dna Encoding ◽  
Transcription Activator ◽  
Xanthomonas Citri ◽  
Suicide Vector ◽  
In Trans ◽  
Highly Virulent

Abstract Background Bacterial blight of cotton (BBC), which is incited by Xanthomonas citri pv. malvacearum ( Xcm ), is a destructive disease in cotton. Transcription activator-like effectors (TALEs), encoded by tal -genes, play critical roles in the pathogenesis of xanthomonads. Characterized strains of cotton pathogenic Xcm harbor 6-13 different tal genes and only one of them is functionally decoded. Further identification of novel tal genes in Xcm strains with virulence contributions are prerequisite to decipher the Xcm -cotton interactionsResults In this study, we identified six tal genes in Xss-V 2 -18, a highly-virulent strain of Xcm from China, and assessed their role in BBC. RFLP-based Southern hybridization assays indicated that Xss-V 2 -18 harbors the six tal genes on a plasmid. The plasmid-encoded tal genes were isolated by cloning Bam HI fragments and screening clones by colony hybridization. The tal genes were sequenced by inserting a Tn 5 transposon in the DNA encoding the central repeat region (CRR) of each tal gene. Xcm TALome evolutionary relationship based on TALEs CRR revealed relatedness of Xss-V 2 -18 to MSCT1 and MS14003 from the United States. However, Tal2 of Xss-V 2 -18 differs at two repeat variable diresidues (RVDs) from Tal6 and Tal26 in MSCT1 and MS14003, respectively, inferred functional dissimilarity. The suicide vector pKMS1 was then used to construct tal deletion mutants in Xcm Xss-V 2 -18. The mutants were evaluated for pathogenicity in cotton based on symptomology and growth in planta . Four mutants showed attenuated virulence and all contained mutations in tal2 . One tal2 mutant designated M2 was further investigated in complementation assays. When tal2 was introduced into Xcm M2 and expressed in trans , the mutant was complemented for both symptoms and growth in planta , thus indicating that tal2 functions as a virulence factor in Xcm Xss-V 2 -18.Conclusions Overall, the results demonstrated that Tal2 is a major pathogenicity factor in Xcm strain Xss-V 2 -18 that contributes significantly in BBC. This study provides a foundation for future efforts aimed at identifying susceptibility genes in cotton that are targeted by Tal2.

scholarly journals In Vitro Activity and Potency of the Novel Oxazolidinone Contezolid (MRX-I) Tested against Gram-Positive Clinical Isolates from the United States and Europe

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Cecilia G. Carvalhaes ◽  
Leonard R. Duncan ◽  
Wen Wang ◽  
Helio S. Sader
Keyword(s):  
Antibacterial Agent ◽  
The United States ◽  
Clinical Development ◽  
Clinical Isolates ◽  
The Novel ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Content Type ◽  
Vancomycin Resistant

ABSTRACT Contezolid, a new oxazolidinone antibacterial agent currently in development for the treatment of skin and skin structure infections, was susceptibility tested against Gram-positive clinical isolates (n = 1,211). Contezolid demonstrated potent activity against Staphylococcus aureus (MIC50/90, 0.5/1 mg/liter), coagulase-negative Staphylococcus (MIC50/90, 0.25/0.5 mg/liter), Enterococcus spp. (MIC50/90, 0.5/1 mg/liter), and streptococci (MIC50/90, 1/1 mg/liter). Moreover, methicillin-resistant S. aureus and vancomycin-resistant Enterococcus faecium isolates were all inhibited by contezolid at ≤1 mg/liter. These results support the clinical development of contezolid.

Report of the Task Force To Establish Guidelines for Pediatric Pulmonary Training

PEDIATRICS ◽  
1978 ◽  
Vol 62 (2) ◽  
pp. 256-257
Keyword(s):  
Lung Disease ◽  
Pulmonary Disease ◽  
Task Force ◽  
The United States ◽  
Pediatric Age ◽  
Pediatric Chest ◽  
Manpower Needs ◽  
Age Range ◽  
Pediatric Lung Disease ◽  
Insufficient Number

The present recommendations of the Task Force stem from a growing awareness of the magnitude of pulmonary disease over the entire pediatric age range and the concern that there is an insufficient number of programs capable of providing the broad training in acute and chronic lung disease required to meet the current challenge in the United States. The magnitude of pediatric lung disease has been documented by the preceding report of the Task Force on Scope and Professional Manpower Needs in Pediatric Respiratory Disease (p. 254). The seriousness of the shortage of pediatric chest physicians has already been suggested by a recent Pulmonary Disease Manpower Survey.1

scholarly journals Antimicrobial Resistance among Clinical Isolates ofStreptococcus pneumoniae in the United States during 1999–2000, Including a Comparison of Resistance Rates since 1994–1995

2001 ◽  
Vol 45 (6) ◽  
pp. 1721-1729 ◽  
Author(s):  
Gary V. Doern ◽  
Kristopher P. Heilmann ◽  
Holly K. Huynh ◽  
Paul R. Rhomberg ◽  
Stacy L. Coffman ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Rank Order ◽  
The United States ◽  
Clinical Isolates ◽  
Beta Lactam ◽  
High Level ◽  
Resistance Rates

ABSTRACT A total of 1,531 recent clinical isolates of Streptococcus pneumoniae were collected from 33 medical centers nationwide during the winter of 1999–2000 and characterized at a central laboratory. Of these isolates, 34.2% were penicillin nonsusceptible (MIC ≥ 0.12 μg/ml) and 21.5% were high-level resistant (MIC ≥ 2 μg/ml). MICs to all beta-lactam antimicrobials increased as penicillin MICs increased. Resistance rates among non-beta-lactam agents were the following: macrolides, 25.2 to 25.7%; clindamycin, 8.9%; tetracycline, 16.3%; chloramphenicol, 8.3%; and trimethoprim-sulfamethoxazole (TMP-SMX), 30.3%. Resistance to non-beta-lactam agents was higher among penicillin-resistant strains than penicillin-susceptible strains; 22.4% of S. pneumoniae were multiresistant. Resistance to vancomycin and quinupristin-dalfopristin was not detected. Resistance to rifampin was 0.1%. Testing of seven fluoroquinolones resulted in the following rank order of in vitro activity: gemifloxacin > sitafloxacin > moxifloxacin > gatifloxacin > levofloxacin = ciprofloxacin > ofloxacin. For 1.4% of strains, ciprofloxacin MICs were ≥4 μg/ml. The MIC90s (MICs at which 90% of isolates were inhibited) of two ketolides were 0.06 μg/ml (ABT773) and 0.12 μg/ml (telithromycin). The MIC90 of linezolid was 2 μg/ml. Overall, antimicrobial resistance was highest among middle ear fluid and sinus isolates of S. pneumoniae; lowest resistance rates were noted with isolates from cerebrospinal fluid and blood. Resistant isolates were most often recovered from children 0 to 5 years of age and from patients in the southeastern United States. This study represents a continuation of two previous national studies, one in 1994–1995 and the other in 1997–1998. Resistance rates with S. pneumoniae have increased markedly in the United States during the past 5 years. Increases in resistance from 1994–1995 to 1999–2000 for selected antimicrobial agents were as follows: penicillin, 10.6%; erythromycin, 16.1%; tetracycline, 9.0%; TMP-SMX, 9.1%; and chloramphenicol, 4.0%, the increase in multiresistance was 13.3%. Despite awareness and prevention efforts, antimicrobial resistance with S. pneumoniae continues to increase in the United States.

scholarly journals AB5075, a Highly Virulent Isolate of Acinetobacter baumannii, as a Model Strain for the Evaluation of Pathogenesis and Antimicrobial Treatments

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Anna C. Jacobs ◽  
Mitchell G. Thompson ◽  
Chad C. Black ◽  
Jennifer L. Kessler ◽  
Lily P. Clark ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Animal Models ◽  
Acinetobacter Baumannii ◽  
Survival Rates ◽  
The United States ◽  
Clinical Isolates ◽  
Suitable Model ◽  
Content Type ◽  
Highly Virulent ◽  
Model Strain

ABSTRACT Acinetobacter baumannii is recognized as an emerging bacterial pathogen because of traits such as prolonged survival in a desiccated state, effective nosocomial transmission, and an inherent ability to acquire antibiotic resistance genes. A pressing need in the field of A. baumannii research is a suitable model strain that is representative of current clinical isolates, is highly virulent in established animal models, and can be genetically manipulated. To identify a suitable strain, a genetically diverse set of recent U.S. military clinical isolates was assessed. Pulsed-field gel electrophoresis and multiplex PCR determined the genetic diversity of 33 A. baumannii isolates. Subsequently, five representative isolates were tested in murine pulmonary and Galleria mellonella models of infection. Infections with one strain, AB5075, were considerably more severe in both animal models than those with other isolates, as there was a significant decrease in survival rates. AB5075 also caused osteomyelitis in a rat open fracture model, while another isolate did not. Additionally, a Tn5 transposon library was successfully generated in AB5075, and the insertion of exogenous genes into the AB5075 chromosome via Tn7 was completed, suggesting that this isolate may be genetically amenable for research purposes. Finally, proof-of-concept experiments with the antibiotic rifampin showed that this strain can be used in animal models to assess therapies under numerous parameters, including survival rates and lung bacterial burden. We propose that AB5075 can serve as a model strain for A. baumannii pathogenesis due to its relatively recent isolation, multidrug resistance, reproducible virulence in animal models, and genetic tractability. IMPORTANCE The incidence of A. baumannii infections has increased over the last decade, and unfortunately, so has antibiotic resistance in this bacterial species. A. baumannii is now responsible for more than 10% of all hospital-acquired infections in the United States and has a >50% mortality rate in patients with sepsis and pneumonia. Most research on the pathogenicity of A. baumannii focused on isolates that are not truly representative of current multidrug-resistant strains isolated from patients. After screening of a panel of isolates in different in vitro and in vivo assays, the strain AB5075 was selected as more suitable for research because of its antibiotic resistance profile and increased virulence in animal models. Moreover, AB5075 is susceptible to tetracycline and hygromycin, which makes it amenable to genetic manipulation. Taken together, these traits make AB5075 a good candidate for use in studying virulence and pathogenicity of this species and testing novel antimicrobials.

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