Rifampin-resistance-associated mutations in the rifampin-resistance-determining region of the rpoB gene of Mycobacterium tuberculosis clinical isolates in Shanghai, PR China

Introduction. Resistance to rifampin (RIF) in Mycobacterium tuberculosis infection is associated with mutations in the rpoB gene coding for the β-subunit of RNA polymerase. The contribution of various rpoB mutations to the development and level of RIF resistance remains elusive. Hypothesis/Gap Statement. Various rpoB mutations may be associated with differential levels of RIF resistance. Aim. This study aimed to investigate the relationship between specific rpoB mutations and the MICs of RIF and rifabutin (RFB) against M. tuberculosis . Methodology. Of the 195 clinical isolates, 105 and 90 isolates were randomly selected from isolates resistant to RIF and sensitive to RIF, respectively. The MICs of 12 agents for M. tuberculosis isolates were determined using commercial Sensititre M. tuberculosis MIC plates and the broth microdilution method. Strains were screened for rpoB mutations by DNA extraction, rpoB gene amplification and DNA sequence analysis. Results. One hundred isolates (95.24 %) were found to have mutations in the RIF-resistance-determining region (RRDR) of the rpoB gene. Three rpoB mutations were identified in 90 RIF-susceptible isolates. Out of 105 isolates, 86 (81.90 %) were cross-resistant to both RIF and RFB. The most frequent mutation occurred at codons 450 and 445. We also found a novel nine-nucleotide (ATCATGCAT) deletion (between positions 1543 and 1551) in the rpoB gene in two strains (1.90 %) with resistance to RIF, but susceptibility to RFB. In addition, the mutation frequency at codon 450 was significantly higher in RIF-resistant/RFB-resistant (RIFR/RFBR) strains than in RIFR/RFBS strains (75.58 % versus 21.05 %, P<0.01), whereas the mutation frequency at codon 435 was significantly lower in RIFR/RFBR strains than in RIFR/RFBS strains (1.16 % versus 26.32 %, P<0.01). Conclusion. Our data support previous findings, which reported that various rpoB mutations are associated with differential levels of RIF resistance. The specific mutations in the rpoB gene in RIFR/RFBR isolates differed from those in the RIFR/RFBS isolates. A novel deletion mutation in the RRDR might be associated with resistance to RIF, but not to RFB. Further clinical studies are required to investigate the efficacy of RFB in the treatment of infections caused by M. tuberculosis strains harbouring these mutations.

Download Full-text

Rifampin resistance-associated mutations in the RIF resistance-determining region (RRDR) of the rpoB gene of Mycobacterium tuberculosis clinical isolates in Shanghai, China

10.21203/rs.2.11840/v1 ◽

2019 ◽

Author(s):

Yinjuan Guo ◽

Xingwei Cao ◽

Jinghui Yang ◽

Xiaocui Wu ◽

Yin Liu ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Mutation Frequency ◽

Rpob Gene ◽

Clinical Isolates ◽

Sequencing Analysis ◽

Mycobacterium Tuberculosis Infection ◽

Gene Coding ◽

Rifampin Resistance ◽

Dna Sequencing Analysis ◽

The Relationship

Abstract Background: Resistance to rifampin (RIF) in Mycobacterium tuberculosis infection is associated with mutations in the rpoB gene coding for the beta-subunit of RNA polymerase. The contribution of many individual rpoB mutations to the development and level of RIF resistance remains elusive. Our objective for this study was to investigate the relationship between specific rpoB mutations and the minimum inhibitory concentrations (MICs) of RIF and rifabutin (RFB) against M.tuberculosis. Methods: We collected 195 clinical isolates of M. tuberculosis including 105 RIF-resistant and 90 RIF-susceptible isolates from Shanghai Pulmonary Hospital in China. The MICs of antituberculosis drugs in 7H10 Middlebrook medium for clinical isolates of M. tuberculosis were determined. Strains were screened for rpoB mutations by DNA extraction, rpoB gene amplification, and DNA sequencing analysis. Results: Twenty different types of mutations were identified in the rpoB gene. One hundred isolates (95.24%) were found to have mutations in the RIF resistance-determining region (RRDR) of the rpoB gene. Three rpoB mutations were identified in 90 RIF-susceptible isolates. Out of 105 isolates, 86 (81.90%) were cross-resistant to both RIF and RFB. The most frequent mutation occurred at codon 531 (65.71%), followed by 526 (8.57%). We also found a novel nine-nucleotide (ATCATGCAT) deletion (between positions 1543 and 1551) in the rpoB gene among two strains (1.90%) with resistance to RIF, but susceptibility to RFB. In addition, the mutation frequency at codon 531 was significantly higher in RIF-resistant/RFB-resistant (RIFR/RFBR) strains than in RIFR/RFBS strains (75.58% versus 21.05%), whereas the mutation frequency at codon 516 was significantly lower in RIFR/RFBR strains than in RIFR/RFBS strains (1.16% versus 26.32%). The MICs of RIF against 87.62% (92/105) of the M.tuberculosis isolates were ≥ 16 µg/mL. Conclusions: Our data supported previous findings that various rpoB mutations are associated with differential levels of resistance to RIF. The specific mutations of the rpoB gene in RIFR/RFBR isolates differed from those in RIFR/RFBS isolates. A novel deletion mutation in the RRDR might be associated with resistance to RIF, but not to RFB. Further clinical studies are required to investigate the efficacy of RFB in the treatment of M. tuberculosis infections, which harbor the mutations.

Download Full-text

Pathogenomic analyses of Mycobacterium microti, an ESX-1-deleted member of the Mycobacterium tuberculosis complex causing disease in various hosts

Microbial Genomics ◽

10.1099/mgen.0.000505 ◽

2021 ◽

Vol 7 (2) ◽

Author(s):

Mickael Orgeur ◽

Wafa Frigui ◽

Alexandre Pawlik ◽

Simon Clark ◽

Ann Williams ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Guinea Pig ◽

Type Species ◽

Clinical Isolates ◽

Recent Common Ancestor ◽

Genome Sequences ◽

Content Type ◽

Link Type ◽

Vaccine Potential ◽

Mycobacterium Microti

Mycobacterium microti is an animal-adapted member of the Mycobacterium tuberculosis complex (MTBC), which was originally isolated from voles, but has more recently also been isolated from other selected mammalian hosts, including occasionally from humans. Here, we have generated and analysed the complete genome sequences of five representative vole and clinical M. microti isolates using PacBio- and Illumina-based technologies, and have tested their virulence and vaccine potential in SCID (severe combined immune deficient) mouse and/or guinea pig infection models. We show that the clinical isolates studied here cluster separately in the phylogenetic tree from vole isolates and other clades from publicly available M. microti genome sequences. These data also confirm that the vole and clinical M. microti isolates were all lacking the specific RD1mic region, which in other tubercle bacilli encodes the ESX-1 type VII secretion system. Biochemical analysis further revealed marked phenotypic differences between isolates in type VII-mediated secretion of selected PE and PPE proteins, which in part were attributed to specific genetic polymorphisms. Infection experiments in the highly susceptible SCID mouse model showed that the clinical isolates were significantly more virulent than the tested vole isolates, but still much less virulent than the M. tuberculosis H37Rv control strain. The strong attenuation of the ATCC 35872 vole isolate in immunocompromised mice, even compared to the attenuated BCG (bacillus Calmette–Guérin) vaccine, and its historic use in human vaccine trials encouraged us to test this strain’s vaccine potential in a guinea pig model, where it demonstrated similar protective efficacy as a BCG control, making it a strong candidate for vaccination of immunocompromised individuals in whom BCG vaccination is contra-indicated. Overall, we provide new insights into the genomic and phenotypic variabilities and particularities of members of an understudied clade of the MTBC, which all share a recent common ancestor that is characterized by the deletion of the RD1mic region.

Download Full-text

Status of rpoB gene mutation associated with rifampicin-resistant Mycobacterium tuberculosis isolated in a rural setting in Nepal

Access Microbiology ◽

10.1099/acmi.0.000202 ◽

2021 ◽

Author(s):

Saroj Adhikari ◽

Bhuvan Saud ◽

Sunil Sunar ◽

Sheshraj Ghimire ◽

Bhawani Prasad Yadav

Keyword(s):

Mycobacterium Tuberculosis ◽

Type Species ◽

Bacterial Load ◽

Latent Tuberculosis ◽

Rpob Gene ◽

Rural Setting ◽

Molecular Technique ◽

Content Type ◽

Link Type

Mycobacterium tuberculosis ranks among the top 10 causes of deaths in Nepal despite the country having a long history of national tuberculosis prevention programmes that have proved very successful in the control of tuberculosis. Several cases of active or latent tuberculosis are still missing despite that the number of infected individuals is increasing each year. Microscopy has its own limitations and factors like low bacterial load, quality of sample, quality of smear, experience of microscopist etc. influence the overall sensitivity of the test. The implementation of a molecular technique-based rapid, point-of-care testing system offers higher sensitivity in the early diagnosis of tuberculosis. Cepheid GeneXpert is the most commonly used molecular technology in Nepal. It is a cartridge-based semi-quantitative, nested real-time PCR-based diagnostic system. It detects mutations in the beta-subunit of RNA polymerase (rpoB) gene that lead to rifampicin resistance (RR) in M. tuberculosis complex. The present study aims to increase our understanding of the epidemiology of mutations in the rpoB gene in tuberculosis-positive patients by using the Xpert MTB/RIF assay in a rural setting in Pyuthan Hospital, Nepal. Sputum from 2733 patients was tested for the diagnosis of tuberculosis using the Cepheid GeneXpert system between July 2018 and January 2020 at Pyuthan Hospital. Two hundred and ninety-seven of these samples (10.86 %) were positive for M. tuberculosis , of which 3.3 % (10/297) were rifampicin-resistant. Among rifampicin-resistant tuberculosis (RR-TB) patients, 50.0 % (5/10) showed mutations located in codons 529–533 (probe E) of the rpoB gene, followed by others. The GeneXpert system can be a convenient, highly sensitive, rapid and accurate tool for the diagnosis of tuberculosis, also identifying RR-TB and at the same time determining the molecular epidemiology of rifampin resistance-associated mutations in rural and/or resource-limited laboratory settings.

Download Full-text

In Vitro Activities of the Novel Oxazolidinones DA-7867 and DA-7157 against Rapidly and Slowly Growing Mycobacteria

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00763-06 ◽

2006 ◽

Vol 50 (12) ◽

pp. 4027-4029 ◽

Cited By ~ 18

Author(s):

Lucio Vera-Cabrera ◽

Barbara A. Brown-Elliott ◽

Richard J. Wallace ◽

Jorge Ocampo-Candiani ◽

Oliverio Welsh ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Clinical Isolates ◽

Nontuberculous Mycobacterium ◽

The Novel ◽

Broth Microdilution ◽

Reference Species ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Aerobic Actinomycetes

ABSTRACT DA-7867 and DA-7157 are oxazolidinones active against pathogenic aerobic actinomycetes including Nocardia spp. and Mycobacterium tuberculosis. However, the activity of these drugs against nontuberculous mycobacterium (NTM) species is not known. In this work, we compared the susceptibilities of 122 clinical isolates and 29 reference species of both rapidly growing and slowly growing mycobacteria to linezolid, DA-7867, and DA-7157 by the broth microdilution method. The MICs for 50 and 90% of the strains tested (MIC50s and MIC90s, respectively) of DA-7867 and DA-7157 were lower than those of linezolid. In all of the cases, a MIC90 of <8 μg/ml was observed for all of the species tested in both groups of NTM. For M. kansasii and M. marinum isolates, the MIC90s of both DA-7867 and DA-7157 were less than 0.5 μg/ml. These results demonstrate the potential of these compounds to treat NTM infections.

Download Full-text

Prevalence of Antimicrobial Resistance among Clinical Isolates of Bacteroides fragilis Group in Canada in 2010-2011: CANWARD Surveillance Study

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05823-11 ◽

2011 ◽

Vol 56 (3) ◽

pp. 1247-1252 ◽

Cited By ~ 58

Author(s):

James A. Karlowsky ◽

Andrew J. Walkty ◽

Heather J. Adam ◽

Melanie R. Baxter ◽

Daryl J. Hoban ◽

...

Keyword(s):

Antimicrobial Agents ◽

Bacteroides Fragilis ◽

Clinical Isolates ◽

Surveillance Study ◽

Content Type ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Amoxicillin Clavulanate ◽

Bacteroides Fragilis Group ◽

Bacteroides Ovatus

ABSTRACTClinical isolates of theBacteroides fragilisgroup (n= 387) were collected from patients attending nine Canadian hospitals in 2010-2011 and tested for susceptibility to 10 antimicrobial agents using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method.B. fragilis(59.9%),Bacteroides ovatus(16.3%), andBacteroides thetaiotaomicron(12.7%) accounted for ∼90% of isolates collected. Overall rates of percent susceptibility were as follows: 99.7%, metronidazole; 99.5%, piperacillin-tazobactam; 99.2%, imipenem; 97.7%, ertapenem; 92.0%, doripenem; 87.3%, amoxicillin-clavulanate; 80.9%, tigecycline; 65.9%, cefoxitin; 55.6%, moxifloxacin; and 52.2%, clindamycin. Percent susceptibility to cefoxitin, clindamycin, and moxifloxacin was lowest forB. thetaiotaomicron(n= 49, 24.5%),Parabacteroides distasonis/P. merdae(n= 11, 9.1%), andB. ovatus(n= 63, 31.8%), respectively. One isolate (B. thetaiotaomicron) was resistant to metronidazole, and two isolates (bothB. fragilis) were resistant to both piperacillin-tazobactam and imipenem. Since the last published surveillance study describing Canadian isolates ofB. fragilisgroup almost 20 years ago (A.-M. Bourgault et al., Antimicrob. Agents Chemother. 36:343–347, 1992), rates of resistance have increased for amoxicillin-clavulanate, from 0.8% (1992) to 6.2% (2010-2011), and for clindamycin, from 9% (1992) to 34.1% (2010-2011).

Download Full-text

Stenotrophomonas maltophilia phenotypic and genotypic features through 4-year cystic fibrosis lung colonization

Journal of Medical Microbiology ◽

10.1099/jmm.0.001281 ◽

2020 ◽

Author(s):

Eliana Alcaraz ◽

Daniela Centrón ◽

Gabriela Camicia ◽

María Paula Quiroga ◽

José Di Conza ◽

...

Keyword(s):

Cystic Fibrosis ◽

Adult Patient ◽

Virulence Factors ◽

Stenotrophomonas Maltophilia ◽

Type Species ◽

Mutation Frequency ◽

Content Type ◽

Link Type ◽

Clonal Relatedness ◽

Over Time

Introduction. Stenotrophomonas maltophilia has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established. Hypothesis. Sequential isolates of S. maltophilia from a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors. Aim. To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequential S. maltophilia isolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018. Methodology. The antibiotic resistance of 11 S. maltophilia isolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC–RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates. Results. Seven S. maltophilia isolates were resistant to trimethoprim–sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time. XbaI PFGE revealed that seven isolates belong to two related clones. All isolates were RpfC–RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplified stmPr1 and stmPr2 genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance. Conclusion. The present study shows the long-time persistence of two related S. maltophilia clones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.

Download Full-text

Biochemical and functional characterization of Mycobacterium tuberculosis ketol-acid reductoisomerase

Microbiology ◽

10.1099/mic.0.001087 ◽

2021 ◽

Vol 167 (9) ◽

Author(s):

Nirbhay Singh ◽

Anu Chauhan ◽

Ram Kumar ◽

Sudheer Kumar Singh

Keyword(s):

Amino Acids ◽

Mycobacterium Tuberculosis ◽

Type Species ◽

Low Ph ◽

Stress Conditions ◽

Starvation Stress ◽

Content Type ◽

E Coli ◽

Link Type

Branched-chain amino acids (BCAAs) are essential amino acids, but their biosynthetic pathway is absent in mammals. Ketol-acid reductoisomerase (IlvC) is a BCAA biosynthetic enzyme that is coded by Rv3001c in Mycobacterium tuberculosis H37Rv (Mtb-Rv) and MRA_3031 in M. tuberculosis H37Ra (Mtb-Ra). IlvCs are essential in Mtb-Rv as well as in Escherichia coli . Compared to wild-type and IlvC-complemented Mtb-Ra strains, IlvC knockdown strain showed reduced survival at low pH and under low pH+starvation stress conditions. Further, increased expression of IlvC was observed under low pH and starvation stress conditions. Confirmation of a role for IlvC in pH and starvation stress was achieved by developing E. coli BL21(DE3) IlvC knockout, which was defective for growth in M9 minimal medium, but growth could be rescued by isoleucine and valine supplementation. Growth was also restored by complementing with over-expressing constructs of Mtb-Ra and E. coli IlvCs. The E. coli knockout also had a survival deficit at pH=5.5 and 4.5 and was more susceptible to killing at pH=3.0. The biochemical characterization of Mtb-Ra and E. coli IlvCs confirmed that both have NADPH-dependent activity. In conclusion, this study demonstrates the functional complementation of E. coli IlvC by Mtb-Ra IlvC and also suggests that IlvC has a role in tolerance to low pH and starvation stress.

Download Full-text

Difference in drug susceptibility distribution and clinical characteristics between Mycobacterium avium and Mycobacterium intracellulare lung diseases in Shanghai, China

Journal of Medical Microbiology ◽

10.1099/jmm.0.001358 ◽

2021 ◽

Vol 70 (5) ◽

Author(s):

Weiping Wang ◽

Jinghui Yang ◽

Xiaocui Wu ◽

Baoshan Wan ◽

Hongxiu Wang ◽

...

Keyword(s):

Mycobacterium Avium ◽

Antimicrobial Susceptibility ◽

Type Species ◽

Clinical Characteristics ◽

Radiographic Findings ◽

Content Type ◽

Mycobacterium Intracellulare ◽

Link Type ◽

Broth Microdilution Method ◽

Significant Difference

Introduction. Mycobacterium avium complex (MAC) has been reported as the most common aetiology of lung disease involving nontuberculous mycobacteria. Hypothesis. Antimicrobial susceptibility and clinical characteristics may differ between Mycobacterium avium and Mycobacterium intracellulare . Aim. We aimed to evaluate the differences in antimicrobial susceptibility profiles between two major MAC species ( Mycobacterium avium and Mycobacterium intracellulare ) from patients with pulmonary infections and to provide epidemiologic data with minimum inhibitory concentration (MIC) distributions. Methodology. Between January 2019 and May 2020, 45 M. avium and 242 M . intracellulare isolates were obtained from Shanghai Pulmonary Hospital. The demographic and clinical characteristics of patients were obtained from their medical records. The MICs of 13 antimicrobials were determined for the MAC isolates using commercial Sensititre SLOWMYCO MIC plates and the broth microdilution method, as recommended by the Clinical and Laboratory Standards Institute (CLSI; Standards M24-A2). MIC50 and MIC90 values were derived from the MIC distributions. Results. M. intracellulare had higher resistance rates than M. avium for most tested antimicrobials except clarithromycin, ethambutol, and ciprofloxacin. Clarithromycin was the most effective antimicrobial against both the M. avium (88.89 %) and M. intracellulare (91.32 %) isolates, with no significant difference between the species (P=0.601). The MIC90 of clarithromycin was higher for M. avium (32 µg ml−1) than M. intracellulare (8 µg ml−1). The MIC50 of rifabutin was more than four times higher for M. intracellulare (1 µg ml−1) than M. avium (≤0.25 µg ml−1). The percentages of patients aged >60 years and patients with sputum, cough, and cavitary lesions were significantly higher than among patients with M. intracellulare infection than M. avium infections. Conclusions. The pulmonary disease caused by distinct MAC species had different antimicrobial susceptibility, symptoms, and radiographic findings.

Download Full-text

In Vitro Activity of Eravacycline against Gram-Positive Bacteria Isolated in Clinical Laboratories Worldwide from 2013 to 2017

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01715-19 ◽

2019 ◽

Vol 64 (3) ◽

Cited By ~ 1

Author(s):

Ian Morrissey ◽

Stephen Hawser ◽

Sibylle H. Lob ◽

James A. Karlowsky ◽

Matteo Bassetti ◽

...

Keyword(s):

Antimicrobial Agents ◽

Clinical Isolates ◽

Gram Positive ◽

Content Type ◽

Gram Positive Bacteria ◽

Microdilution Method ◽

Clinical Laboratories ◽

Broth Microdilution Method ◽

Doubling Dilution

ABSTRACT Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, including those caused by resistant Gram-positive pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a recent global collection of frequently encountered clinical isolates of Gram-positive bacteria. The CLSI broth microdilution method was used to determine in vitro MIC data for isolates of Enterococcus spp. (n = 2,807), Staphylococcus spp. (n = 4,331), and Streptococcus spp. (n = 3,373) isolated primarily from respiratory, intra-abdominal, urinary, and skin specimens by clinical laboratories in 37 countries on three continents from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. There were no substantive differences (a >1-doubling-dilution increase or decrease) in eravacycline MIC90 values for different species/organism groups over time or by region. Eravacycline showed MIC50 and MIC90 results of 0.06 and 0.12 μg/ml, respectively, when tested against Staphylococcus aureus, regardless of methicillin susceptibility. The MIC90 values of eravacycline for Staphylococcus epidermidis and Staphylococcus haemolyticus were equal (0.5 μg/ml). The eravacycline MIC90s for Enterococcus faecalis and Enterococcus faecium were 0.06 μg/ml and were within 1 doubling dilution regardless of the vancomycin susceptibility profile. Eravacycline exhibited MIC90 results of ≤0.06 μg/ml when tested against Streptococcus pneumoniae and beta-hemolytic and viridans group streptococcal isolates. In this surveillance study, eravacycline demonstrated potent in vitro activity against frequently isolated clinical isolates of Gram-positive bacteria (Enterococcus, Staphylococcus, and Streptococcus spp.), including isolates collected over a 5-year period (2013 to 2017), underscoring its potential benefit in the treatment of infections caused by common Gram-positive pathogens.

Download Full-text

Results from the China Antimicrobial Surveillance Network (CHINET) in 2017 of the In Vitro Activities of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02431-18 ◽

2019 ◽

Vol 63 (4) ◽

Cited By ~ 19

Author(s):

Dandan Yin ◽

Shi Wu ◽

Yang Yang ◽

Qingyu Shi ◽

Dong Dong ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Clinical Isolates ◽

Surveillance Network ◽

Content Type ◽

Highly Active ◽

Microdilution Method ◽

Carbapenem Resistant ◽

Antimicrobial Surveillance ◽

Broth Microdilution Method

ABSTRACT The in vitro activities of ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C-T), and comparators were determined for 1,774 isolates of Enterobacteriaceae and 524 isolates of Pseudomonas aeruginosa collected by 30 medical centers from the China Antimicrobial Surveillance Network (CHINET) in 2017. Antimicrobial susceptibility testing was performed by the CLSI broth microdilution method, and blaKPC and blaNDM were detected by PCR for all carbapenem-resistant Enterobacteriaceae (CRE). Ceftazidime-avibactam demonstrated potent activity against almost all Enterobacteriaceae (94.6% susceptibility; MIC50, ≤0.25 mg/liter; MIC90, ≤0.25 to >32 mg/liter) and good activity against P. aeruginosa (86.5% susceptibility; MIC50/90, 2/16 mg/liter). Among the CRE, 50.8% (189/372 isolates) were positive for blaKPC-2, which mainly existed in ceftazidime-avibactam-susceptible Klebsiella pneumoniae isolates (92.1%, 174/189). Among the CRE, 17.7% (66/372 isolates) were positive for blaNDM, which mainly existed in strains resistant to ceftazidime-avibactam (71.7%, 66/92). Ceftolozane-tazobactam showed good in vitro activity against Escherichia coli and Proteus mirabilis (MIC50/90, ≤0.5/2 mg/liter; 90.5 and 93.8% susceptibility, respectively), and the rates of susceptibility of K. pneumoniae (MIC50/90, 2/>64 mg/liter) and P. aeruginosa (MIC50/90, 1/8 mg/liter) were 52.7% and 88.5%, respectively. Among the CRE strains, 28.6% of E. coli isolates and 85% of K. pneumoniae isolates were still susceptible to ceftazidime-avibactam, but only 7.1% and 1.9% of them, respectively, were susceptible to ceftolozane-tazobactam. The rates of susceptibility of the carbapenem-resistant P. aeruginosa isolates to ceftazidime-avibactam (65.7%) and ceftolozane-tazobactam (68%) were similar. Overall, both ceftazidime-avibactam and ceftolozane-tazobactam were highly active against clinical isolates of Enterobacteriaceae and P. aeruginosa recently collected across China, and ceftazidime-avibactam showed activity superior to that of ceftolozane-tazobactam against Enterobacteriaceae, whereas ceftolozane-tazobactam showed a better effect against P. aeruginosa.

Download Full-text