Characterization of Two New Multidrug-Resistant Strains of Mycobacterium smegmatis: Tools for Routine In Vitro Screening of Novel Anti-Mycobacterial Agents

Mycobacterium tuberculosis is a pathogen of global public health concern. This threat is exacerbated by the emergence of multidrug-resistant and extremely-drug-resistant strains of the pathogen. We have obtained two distinct clones of multidrug-resistant Mycobacterium smegmatis after gradual exposure of Mycobacterium smegmatis mc2 155 to increasing concentrations of erythromycin. The resulting resistant strains of Mycobacterium smegmatis exhibited robust viability in the presence of high concentrations of erythromycin and were found to be resistant to a wide range of other antimicrobials. They also displayed a unique growth phenotype in comparison to the parental drug-susceptible Mycobacterium smegmatis mc2 155, and a distinct colony morphology in the presence of cholesterol. We propose that these two multidrug-resistant clones of Mycobacterium smegmatis could be used as model organisms at the inceptive phase of routine in vitro screening of novel antimicrobial agents targeted against multidrug-resistant Mycobacterial tuberculosis.

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1592. In Vitro Activity of Ceftolozane/Tazobactam (C/T) Against Enterobacteriaceae and Pseudomonas aeruginosa Circulating in Chile

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1456 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S581-S581

Author(s):

Lina M Rivas ◽

Jose R W Martínez ◽

Maria Spencer ◽

Lorena Porte ◽

Francisco Silva ◽

...

Keyword(s):

Tertiary Care ◽

Multidrug Resistant ◽

Global Public Health ◽

Health Crisis ◽

Clinical Strains ◽

E Coli ◽

Highly Active ◽

Complex Figure ◽

Wide Range

Abstract Background The widespread dissemination of carbapenem-resistant (CR) P. aeruginosa and Enterobacteriaceae has created a major global public health crisis. C/T is a recently approved therapeutic which consists of the combination of a novel cephalosporin (ceftolozane) and tazobactam (a β-lactamase inhibitor). C/T has shown good activity against a wide range of multidrug-resistant (MDR) Gram negatives, being particularly interesting as an alternative for MDR P. aeruginosa. We aimed to determine the activity of C/T against clinical strains of Enterobacteriaceae and P. aeruginosa recovered in 4 large clinical centers from Chile. Methods We analyzed 434 isolates of Enterobacteriaceae (347 E. coli, 66 K. pneumoniae, 21 Enterobacter cloacae complex) and 57 P. aeruginosa collected during 2017 from 4 tertiary care institutions in Santiago, Chile. Identification was performed as per each local clinical microbiology lab. Susceptibility testing was performed by broth microdilution using customized Sensititre plates (Trek). Carba-NP was performed to screen for carbapenemase production. Susceptibilities were analyzed as per 2019 CLSI breakpoints. Results The MIC50/90 for C/T against Enterobacteriaceae and P. aeruginosa were 1/4 μg/mL and 2/16 μg/mL, respectively. In Enterobacteriaceae, susceptibility to C/T reached 92% in E. coli (Figure 1A), 91% in E. cloacae complex (Figure 1B) and 70% in K. pneumoniae (Figure 1C). Remarkably, C/T remained active against 58% (33/57) of CR Enterobacteriaceae (Figure 2A). Among Carba-NP-negative CR isolates (46%, 26/57), susceptibility to C/T was 54% (Figure 3 A–C). In P. aeruginosa, the overall susceptibility to C/T was 81% (Figure 1D), maintaining activity against 69% (25/36) of CR strains (Figure 2B). Importantly, susceptibility to C/T in CR P. aeruginosa isolates with a negative Carba-NP (67%, 24/36) was 83% (20/24) (Figure 3D). Conclusion In this multicenter study, we observed that C/T was highly active against clinical isolates of Enterobacteriaceae and P. aeruginosa. Of note, C/T remained active against a large proportion of CR clinical strains. Moreover, the activity of C/T was particularly high against CR P. aeruginosa isolates with a negative Carba-NP. Disclosures All authors: No reported disclosures.

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In Vitro Activities of β-Lactam–β-Lactamase Inhibitor Antimicrobial Agents against Cystic Fibrosis Respiratory Pathogens

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01595-19 ◽

2019 ◽

Vol 64 (1) ◽

Cited By ~ 5

Author(s):

Lindsay J. Caverly ◽

Theodore Spilker ◽

Linda M. Kalikin ◽

Terri Stillwell ◽

Carol Young ◽

...

Keyword(s):

Cystic Fibrosis ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Respiratory Pathogens ◽

Content Type ◽

Resistant Strains ◽

Drug Resistant Strains ◽

Increased Activity ◽

Lactamase Inhibitor

ABSTRACT We tested the in vitro activities of ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, piperacillin-tazobactam, and 11 other antimicrobial agents against 420 Burkholderia, Achromobacter, Stenotrophomonas, and Pandoraea strains, 89% of which were cultured from respiratory specimens from persons with cystic fibrosis. Among the β-lactam–β-lactamase inhibitor agents, meropenem-vaborbactam had the greatest activity against Burkholderia and Achromobacter, including multidrug-resistant and extensively-drug-resistant strains. None of the newer β-lactam–β-lactamase combination drugs showed increased activity compared to that of the older agents against Stenotrophomonas maltophilia or Pandoraea spp.

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Antibiotic Therapy of Plague: A Review

Biomolecules ◽

10.3390/biom11050724 ◽

2021 ◽

Vol 11 (5) ◽

pp. 724

Author(s):

Florent Sebbane ◽

Nadine Lemaître

Keyword(s):

Antibiotic Therapy ◽

Case Reports ◽

Multidrug Resistant ◽

Health Concern ◽

Preclinical Studies ◽

Nutritional Immunity ◽

Health Authorities ◽

Predatory Bacteria ◽

Resistant Strains

Plague—a deadly disease caused by the bacterium Yersinia pestis—is still an international public health concern. There are three main clinical forms: bubonic plague, septicemic plague, and pulmonary plague. In all three forms, the symptoms appear suddenly and progress very rapidly. Early antibiotic therapy is essential for countering the disease. Several classes of antibiotics (e.g., tetracyclines, fluoroquinolones, aminoglycosides, sulfonamides, chloramphenicol, rifamycin, and β-lactams) are active in vitro against the majority of Y. pestis strains and have demonstrated efficacy in various animal models. However, some discrepancies have been reported. Hence, health authorities have approved and recommended several drugs for prophylactic or curative use. Only monotherapy is currently recommended; combination therapy has not shown any benefits in preclinical studies or case reports. Concerns about the emergence of multidrug-resistant strains of Y. pestis have led to the development of new classes of antibiotics and other therapeutics (e.g., LpxC inhibitors, cationic peptides, antivirulence drugs, predatory bacteria, phages, immunotherapy, host-directed therapy, and nutritional immunity). It is difficult to know which of the currently available treatments or therapeutics in development will be most effective for a given form of plague. This is due to the lack of standardization in preclinical studies, conflicting data from case reports, and the small number of clinical trials performed to date.

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Carcass Salmonella and Its Drug Resistance

International Journal of Pathogen Research ◽

10.9734/ijpr/2019/v2i130064 ◽

2019 ◽

pp. 1-21

Author(s):

Gizachew Muluneh Amera ◽

Amit Kumar Singh

Keyword(s):

Public Health ◽

Antimicrobial Resistance ◽

Pathogenic Bacteria ◽

Antimicrobial Agents ◽

Public Health Problem ◽

Multidrug Resistant ◽

Health Concern ◽

Personal Hygiene ◽

Wide Range ◽

Food Animals

Salmonella are the major pathogenic bacteria in humans as well as in animals. Salmonella species are leading causes of acute gastroenteritis in several countries and salmonellosis remains an important public health problem worldwide, particularly in the developing countries. Isolation of Salmonella from a wide range of sources suggests that Salmonella is widespread in food animals and meat products and underlines the necessity for a joint and coordinated surveillance and monitoring programs for salmonellosis and other major food borne zoonotic diseases. Food animals harbor a wide range of Salmonella and so act as sources of contamination, which is of paramount epidemiological importance in non-typhoid human salmonellosis. Salmonellosis is more aggravated by the ever increasing rate of antimicrobial resistance strains in food animals. The high prevalence and dissemination of multidrug resistant (MDR) Salmonella have become a growing public health concern. Multidrug resistant (MDR) strains of Salmonella are now encountered frequently and the rates of multidrug resistance have increased considerably in recent years. Food animal consumption is a potential cause for antimicrobial resistant Salmonella illnesses besides, the common factors such as overcrowding, poverty, inadequate sanitary conditions, and poor personal hygiene. Practicing good sanitary measures, extensive education programs for proper hygiene and improvement of managements are solutions to eliminate the high bacteriological load as well as prevalence of Salmonella in cattle carcass. Furthermore, restricting the use of antimicrobial agents in food animals, designation of multidrug-resistant Salmonella as an adulterant in ground beef, improving the mechanisms for product trace-back investigations and wise and discriminate use of antimicrobials should be practiced to combat the ever increasing situation of antimicrobial resistance. So, this review used for updating information on their prevalence and resistance patterns is very important to suggest the acceptance of the carcass in relation to the standards and for proper selection and use of antimicrobial agents in a setting.

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A retrospective observational study of the impact of Tigecycline in treating multidrug resistant pneumonia

International Journal of Clinical Trials ◽

10.18203/2349-3259.ijct20172541 ◽

2017 ◽

Vol 4 (3) ◽

pp. 122

Author(s):

John Paul ◽

Cherish Paul

Keyword(s):

Critically Ill ◽

Meta Analysis ◽

Multidrug Resistant ◽

Health Concern ◽

P Value ◽

Global Public Health ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Background: Few antimicrobials are currently active to treat extensively drug resistant (XDR) gram-negative bacilli infections. This represents a serious global public health concern. Critically ill patients face the brunt of majority of these infections. Tigecycline has coverage for a majority of these XDR infections (with the exception of Pseudomonas aeruginosa), but is not currently approved for hospital-acquired pneumonia. Nevertheless it is being commonly used for this indication though many meta-analysis have suggested an increased risk of death in patients receiving this antibiotic. Methods: In this retrospective analysis we compared the mortality rates between a Tigecycline based and a non Tigecycline based therapy for XDR infections in the critically ill over a period of 12 months. A total of 93 patients were included in the study.Results: Tigecycline group had significantly increased risk for in hospital mortality with an odds ratio of 6.0 and 95% CI of 1.37 to 26.12 with a p value of 0.01. But such a difference was not evident in 14 day mortality. Conclusions: Initiation of Tigecycline for multidrug resistant, pneumonia needs to be re-thought. Only a small percentage of patients with pneumonia with in-vitro sensitivity having low minimum inhibitory concentration (MIC) would benefit from the drug. Even in this group the risk of increased mortality needs to be carefully considered before Initiation of therapy.

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Gyrase A Mutations in Campylobacter Associated with Decreased Susceptibility to Different Fluoroquinolones

Journal of Food Protection ◽

10.4315/0362-028x.jfp-17-129 ◽

2017 ◽

Vol 80 (11) ◽

pp. 1863-1866 ◽

Cited By ~ 2

Author(s):

Chris A. Whitehouse ◽

Shaohua Zhao ◽

Sampa Mukherjee ◽

Heather Tate ◽

Sonya Bodeis-Jones ◽

...

Keyword(s):

Health Concern ◽

Campylobacter Coli ◽

Single Mutation ◽

Global Public Health ◽

Gyra Gene ◽

In Vitro Susceptibility ◽

Fluoroquinolone Antibiotics ◽

Gyrase A ◽

Resistant Strains

ABSTRACT Campylobacter is a leading cause of foodborne diarrheal illness worldwide, and the emergence of antimicrobial-resistant strains is a major global public health concern. The goal of this study was to compare the activity of different fluoroquinolone antibiotics against ciprofloxacin-resistant Campylobacter jejuni and Campylobacter coli. Isolates from retail meats collected between 2002 and 2009 were selected based on their in vitro susceptibility testing results against ciprofloxacin. In total, 289 C. jejuni and 165 C. coli were collected and analyzed. All ciprofloxacin-resistant isolates had a single mutation (Thr86Ile) in their gyrase A (gyrA) gene and exhibited decreased susceptibility to all eight fluoroquinolones tested. Gatifloxacin, enrofloxacin, and levofloxacin showed greater activity than the other fluoroquinolone drugs in both ciprofloxacin-sensitive and -resistant strains.

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Antimicrobial Susceptibilities of Multidrug-Resistant Campylobacter jejuni and C. coli Strains: In Vitro Activities of 20 Antimicrobial Agents

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00898-09 ◽

2009 ◽

Vol 54 (3) ◽

pp. 1232-1236 ◽

Cited By ~ 45

Author(s):

Mirva Lehtopolku ◽

Ulla-Maija Nakari ◽

Pirkko Kotilainen ◽

Pentti Huovinen ◽

Anja Siitonen ◽

...

Keyword(s):

Campylobacter Jejuni ◽

Antimicrobial Agents ◽

Agar Plate ◽

Inhibition Zone ◽

Multidrug Resistant ◽

Dilution Method ◽

Erythromycin Resistance ◽

Disk Diffusion Test ◽

Resistant Strains

ABSTRACT There is a paucity of information regarding antimicrobial agents that are suitable to treat severe infections caused by multidrug-resistant Campylobacter spp. Our aim was to identify agents that are potentially effective against multiresistant Campylobacter strains. The in vitro activities of 20 antimicrobial agents against 238 Campylobacter strains were analyzed by determining MICs by the agar plate dilution method or the Etest. These strains were selected from 1,808 Campylobacter isolates collected from Finnish patients between 2003 and 2005 and screened for macrolide susceptibility by using the disk diffusion test. The 238 strains consisted of 183 strains with erythromycin inhibition zone diameters of ≤23 mm and 55 strains with inhibition zone diameters of >23 mm. Of the 238 Campylobacter strains, 19 were resistant to erythromycin by MIC determinations (MIC ≥ 16 μg/ml). Given that the resistant strains were identified among the collection of 1,808 isolates, the frequency of erythromycin resistance was 1.1%. All erythromycin-resistant strains were multidrug resistant, with 18 (94.7%) of them being resistant to ciprofloxacin (MIC ≥ 4 μg/ml). The percentages of resistance to tetracycline and amoxicillin-clavulanic acid (co-amoxiclav) were 73.7% and 31.6%, respectively. All macrolide-resistant strains were susceptible to imipenem, meropenem, and tigecycline. Ten (52.6%) multiresistant strains were identified as being Campylobacter jejuni strains, and 9 (47.4%) were identified as being C. coli strains. These data demonstrate that the incidence of macrolide resistance was low but that the macrolide-resistant Campylobacter strains were uniformly multidrug resistant. In addition to the carbapenems, tigecycline was also highly effective against these multidrug-resistant Campylobacter strains in vitro. Its efficacy for the treatment of human campylobacteriosis should be evaluated in clinical trials.

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In Vitro Efficacy of Gentamicin Alone and in Combination with Ceftriaxone, Ertapenem, and Azithromycin against Multidrug-Resistant Neisseria gonorrhoeae

Microbiology Spectrum ◽

10.1128/spectrum.00181-21 ◽

2021 ◽

Author(s):

Xuechun Li ◽

Wenjing Le ◽

Xiangdi Lou ◽

Biwei Wang ◽

Caroline A. Genco ◽

...

Keyword(s):

Public Health ◽

Neisseria Gonorrhoeae ◽

Treatment Options ◽

Multidrug Resistant ◽

Health Concern ◽

Global Public Health ◽

Public Health Concern ◽

Content Type ◽

New Treatment

Antimicrobial-resistant Neisseria gonorrhoeae is a major global public health concern. New treatment options are urgently needed to successfully treat multidrug-resistant (MDR) Neisseria gonorrhoeae infections.

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In Vitro Activity of Doripenem (S-4661) against Multidrug-Resistant Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.6.2510-2511.2005 ◽

2005 ◽

Vol 49 (6) ◽

pp. 2510-2511 ◽

Cited By ~ 38

Author(s):

Yunhua Chen ◽

Elizabeth Garber ◽

Qiuqu Zhao ◽

Yigong Ge ◽

Matthew A. Wikler ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Burkholderia Cepacia ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Vitro Activity ◽

In Vitro Activity ◽

Gram Negative ◽

Resistant Strains

ABSTRACT Doripenem 50% inhibitory concentrations (MIC50) and 90% inhibitory concentrations (MIC90) for multidrug-resistant strains of mucoid Pseudomonas aeruginosa (n = 200 strains), nonmucoid P. aeruginosa (n = 200), and Burkholderia cepacia complex (n = 200) isolated from patients with cystic fibrosis were 8 and 32, 8 and 64, and 8 and 32 μg/ml, respectively. Doripenem had somewhat better activity than established antimicrobial agents.

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In-Vitro Efficacy of Cefiderocol in Carbapenem-Non-Susceptible Gram-Negative Bacilli of Different Genotypes in Sub-Region of North Rhine Westphalia, Germany

Pathogens ◽

10.3390/pathogens10101258 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1258

Author(s):

Beniam Ghebremedhin ◽

Parviz Ahmad-Nejad

Keyword(s):

Antimicrobial Agents ◽

Multidrug Resistant ◽

Acinetobacter Baumanii ◽

In Vitro Susceptibility ◽

Gram Negative ◽

Therapy Options ◽

Wide Range ◽

Testing Susceptibility ◽

Species Specific

In the last two decades, the worldwide dissemination of multidrug-resistant Gram-negative bacteria (MDR-GNB) has continued. Therapy options for such infections caused by MDR-GNB remain scarce, and only few new antimicrobial agents have been granted market approval. Cefiderocol has been approved for the treatment of infections associated with aerobic GNB with limited therapy options. This study evaluated the in vitro efficacy of cefiderocol against carbapenem-non-susceptible clinical GNB isolates from Germany. A total of 115 non-duplicate carbapenem-nonsusceptible GNB isolates, 61 (53.05%) of which were Enterobacterales species and 54 (46.95%) were non-fermenters (Acinetobacter baumanii and Pseudomonas aeruginosa), were investigated for their cefiderocol susceptibility. Minimum inhibitory concentrations (MICs) for cefiderocol were determined by disk diffusion, according to EUCAST (European committee for antimicrobial susceptibility testing). Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/-dynamic breakpoints were used. The most common pathogen was A. baumannii (33.91%), followed by Klebsiella pneumoniae (31.3%), P. aeruginosa (13.04%) and Escherichia coli (9.57%). Overall, 83.6% (51/61) of the Enterobacterales and 81.48% (44/54) of the non-fermenters were susceptible towards cefiderocol. In total, 20 species of Enterobacterales and non-fermenting GNB were resistant towards cefiderocol, irrespective of the isolation year (2014 to 2021). Moreover, the majority of the resistant isolates were among the OXA-23 producing A. baumannii (n = 7/26; 26.92%) from patients hospitalized during 2018 and 2019. Cefiderocol demonstrated high in vitro susceptibility rates against a wide range of carbapenem-non-susceptible GNB, including carbapenemase-producing isolates. Cefiderocol exhibited stability against hydrolysis by all carbapenemases, including metallo-β-lactamases (MBLs), except that few OXA-producing isolates exhibited resistance towards cefiderocol.

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