scholarly journals Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant Pseudomonas aeruginosa: A ten-year update

Author(s):  
Ijeoma N. Okoliegbe ◽  
Karolin Hijazi ◽  
Kim Cooper ◽  
Corinne Ironside ◽  
Ian M. Gould

Background: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa. Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti-pseudomonals agents and suggest their most synergistic antimicrobial combinations. ii) to determine antimicrobial resistance rates and study inherent trends of antimicrobials over ten years. Methods: A total of 721 multidrug-resistant P. aeruginosa isolates from 183 patients were collated over the study period. Antimicrobial susceptibility and combination testing were carried out using the Etest method. The results were further assessed using the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI). Results: Resistance to almost all antimicrobial agents maintained a similar level during the studied period. Colistin (p<0.001) and tobramycin (p=0.001) were the only antimicrobials with significant increasing isolate susceptibility while an increasing resistance trend was observed for levofloxacin. The most active antimicrobials were colistin, ceftolozane/tazobactam, ceftazidime/avibactam, and gentamicin. All combinations with β-lactam+β-lactamase inhibitors produced some synergistic results. Ciprofloxacin+ceftolozane/tazobactam (40%) and amikacin+ceftazidime (36.7%) were the most synergistic combinations while colistin combinations gave the best median SPBI (50.11). Conclusions: This study suggests that effective fluoroquinolone stewardship should be employed for CF patients. It also presents in vitro data to support the efficacy of novel combinations for use in the treatment of chronic P. aeruginosa infections.

2021 ◽  
Vol 8 ◽  
Author(s):  
C. V. Tuat ◽  
P. T. Hue ◽  
N. T. P. Loan ◽  
N. T. Thuy ◽  
L. T. Hue ◽  
...  

Antimicrobial use (AMU) and antimicrobial resistance (AMR) are a growing public health and economic threat in Vietnam. We conducted a pilot surveillance programme in five provinces of Vietnam, two in the south and three in the north, to identify antimicrobial resistance (AMR) in rectal swab samples from pigs and fecal samples from chickens at slaughter points during three different points in time from 2017 to 2019. Escherichia coli (E. coli) and non-typhoidal Salmonella (NTS) isolates were tested for antimicrobial susceptibility using disk diffusion assay for 19 antimicrobial agents belonging to nine antimicrobial classes and Etest for colistin (polymyxin). Almost all E. coli (99%; 1029/1042) and NTS (96%; 208/216) isolates were resistant to at least one antimicrobial agent; 94% (981/1042) of E. coli and 89% (193/216) of NTS isolates were multidrug-resistant (MDR). Higher proportions of E. coli and NTS isolated from chickens were resistant to all antimicrobial classes than those isolates from pigs. There was a significantly higher proportion of MDR NTS isolates from the southern provinces of Ho Chi Minh City and Long An (p = 0.008). Although there were increasing trends of NTS in proportion of resistance to fluoroquinolone over the three surveillance rounds, there was a significant decreasing trend of NTS in proportion of resistance to polymyxin (p = 0.002). It is important to establish an annual AMR surveillance program for livestock in Vietnam to assess the impact of interventions, observe trends and drive decision making that ultimately contributes to reducing AMR public health threat.


2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Lindsay J. Caverly ◽  
Theodore Spilker ◽  
Linda M. Kalikin ◽  
Terri Stillwell ◽  
Carol Young ◽  
...  

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.


2001 ◽  
Vol 45 (6) ◽  
pp. 1721-1729 ◽  
Author(s):  
Gary V. Doern ◽  
Kristopher P. Heilmann ◽  
Holly K. Huynh ◽  
Paul R. Rhomberg ◽  
Stacy L. Coffman ◽  
...  

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.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S577-S577
Author(s):  
Cristhian Hernández-Gómez ◽  
Elsa De La Cadena ◽  
Maria F Mojica ◽  
Adriana Correa ◽  
Marcela Perengüez ◽  
...  

Abstract Background Multidrug-resistant Enterobacteriaceae (Ent) and Pseudomonas aeruginosa (Pae) are involved in a considerable number of healthcare-associated infections, thus representing a therapeutic challenge. Ceftolozane–tazobactam (C/T) is a combination of a novel cephalosporin with a known β-lactamase inhibitor. Ceftolozane has high affinity for penicillin-binding proteins, improved outer membrane permeability, increased stability against efflux and enhanced stability against chromosomal AmpC β-lactamases compared with other β-lactam antibiotics. This agent is not active against carbapenemases. We evaluated the in vitro activity of C/T against clinical isolates of Ent and Pae collected from 2016- 2017 and compared it to the activity of broad-spectrum antimicrobial agents. Methods 1.644 Ent and Pae non-duplicate clinical isolates were collected in 13 medical centers located in 12 Colombian cities. Minimum inhibitory concentrations (MIC) were performed by broth microdilution and interpreted according to current CLSI guidelines. Isolates tested included 813 Escherichia coli (Eco), 441 Klebsiella pneumoniae (Kpn), 82 Enterobacter spp., (Enb); 60 Serratia marcescens (Sma) and 248 Pae. Comparator agents were ceftriaxone (CRO), cefotaxime (CTX), ceftazidime (CAZ), cefepime (FEP), piperacillin/tazobactam (TZP), ertapenem (ETP), imipenem (IMI), meropenem (MEM). Results Susceptibilities to C/T and comparators of 4 Ent species and Pae are shown in Table 1. Compared with other β-lactams such as CRO, CAZ, TZP, and FEP, C/T had considerably higher susceptibility rates against ESBL, non-carbapenem-resistant (CR) Eco and Kpn isolates. C/T MIC50/90 were: Eco (≤1/≤1); Kpn (≤1/128); Enb (≤1/64); Sma (≤1/≥256); Pae (≤1/≥256). In the case of P.aeruginosa despite the high resistance rates observed in the study, C/T had the best susceptibility, even higher than the carbapenems. Conclusion Overall, C/T demonstrated higher in vitro activity than currently available cephalosporins and TZP when tested against Ent and Pae. C/T provides an important treatment option against infections caused by non-carbapenemase producing Gram-negative pathogens. Further studies are warranted to identify an emerging mechanism of resistance in Colombia. Disclosures All authors: No reported disclosures.


2021 ◽  
Vol 9 (12) ◽  
pp. 2473
Author(s):  
Clémence Beauruelle ◽  
Claudie Lamoureux ◽  
Arsid Mashi ◽  
Sophie Ramel ◽  
Jean Le Bihan ◽  
...  

Bacteria belonging to the genus Achromobacter are increasingly isolated from respiratory samples of people with cystic fibrosis (PWCF). The management of this multidrug-resistant genus is challenging and characterised by a lack of international recommendations, therapeutic guidelines and data concerning antibiotic susceptibility, especially concerning the newer antibiotics. The objective of this study was to describe the antibiotic susceptibility of Achromobacter isolates from PWCF, including susceptibility to new antibiotics. The minimum inhibitory concentrations (MICs) of 22 antibiotics were determined for a panel of 23 Achromobacter isolates from 19 respiratory samples of PWCF. Two microdilution MIC plates were used: EUMDROXF® plate (Sensititre) and Micronaut-S Pseudomonas MIC® plate (Merlin) and completed by a third method if necessary (E-test® or UMIC®). Among usual antimicrobial agents, the most active was imipenem (70% susceptibility). Trimethoprim-sulfamethoxazole, piperacillin and tigecycline (65%, 56% and 52% susceptibility, respectively) were still useful for the treatment of Achromobacter infections. Among new therapeutic options, β-lactams combined with a β-lactamase-inhibitor did not bring benefits compared to β-lactam alone. On the other hand, cefiderocol appeared as a promising therapeutic alternative for managing Achromobacter infections in PWCF. This study provides the first results on the susceptibility of clinical Achromobacter isolates concerning new antibiotics. More microbiological and clinical data are required to establish the optimal treatment of Achromobacter infections.


2012 ◽  
Vol 140 (11) ◽  
pp. 2074-2081 ◽  
Author(s):  
Y. SASAKI ◽  
A. IKEDA ◽  
K. ISHIKAWA ◽  
M. MURAKAMI ◽  
M. KUSUKAWA ◽  
...  

SUMMARYThis study determined the prevalence and antimicrobial susceptibility of Salmonella isolated from broiler flocks in Japan. Caecal dropping samples were collected from 288 broiler flocks between November 2007 and February 2010. Salmonella was prevalent in 248 (86·1%) broiler flocks. The top three serovars were S. Infantis, S. Manhattan and S. Schwarzengrund. S. Infantis was found in all regions tested in this study. However, S. Manhattan and S. Schwarzengrund were frequently found only in the western part of Japan. High antimicrobial resistance rates were observed against oxytetracycline (90·2%), dihydrostreptomycin (86·7%) and ampicillin (36·5%), and 258 (90·5%) of 285 isolates were resistant to two or more antimicrobial agents. Interestingly, 26·3% of isolates were resistant to ceftiofur, especially 38·1% of S. Infantis isolates, although its use in broilers has not been approved in Japan. This study showed that Salmonella is highly prevalent (86·1%) in Japanese broiler flocks, that 90·5% of Salmonella isolates were multidrug-resistant, and that S. Infantis frequently exhibited resistance to cephalosporin antimicrobial agents.


2002 ◽  
Vol 46 (5) ◽  
pp. 1295-1301 ◽  
Author(s):  
Donald E. Low ◽  
Joyce de Azavedo ◽  
Karl Weiss ◽  
Tony Mazzulli ◽  
Magdalena Kuhn ◽  
...  

ABSTRACT A total of 2,245 clinical isolates of Streptococcus pneumoniae were collected from 63 microbiology laboratories from across Canada during 2000 and characterized at a central laboratory. Of these isolates, 12.4% were not susceptible to penicillin (penicillin MIC, ≥0.12 μg/ml) and 5.8% were resistant (MIC, ≥2 μg/ml). Resistance rates among non-β-lactam agents were the following: macrolides, 11.1%; clindamycin, 5.7%; chloramphenicol, 2.2%; levofloxacin, 0.9%; gatifloxacin, 0.8%; moxifloxacin, 0.4%; and trimethoprim-sulfamethoxazole, 11.3%. The MICs at which 90% of the isolates were inhibited (MIC90s) of the fluoroquinolones were the following: gemifloxacin, 0.03 μg/ml; BMS-284756, 0.06 μg/ml; moxifloxacin, 0.12 μg/ml; gatifloxacin, 0.25 μg/ml; levofloxacin, 1 μg/ml; and ciprofloxacin, 1 μg/ml. Of 578 isolates from the lower respiratory tract, 21 (3.6%) were inhibited at ciprofloxacin MICs of ≥4 μg/ml. None of the 768 isolates from children were inhibited at ciprofloxacin MICs of ≥4 μg/ml, compared to 3 of 731 (0.6%) from those ages 15 to 64 (all of these >60 years old), and 27 of 707 (3.8%) from those over 65. The MIC90s for ABT-773 and telithromycin were 0.015 μg/ml for macrolide-susceptible isolates and 0.12 and 0.5 μg/ml, respectively, for macrolide-resistant isolates. The MIC of linezolid was ≤2 μg/ml for all isolates. Many of the new antimicrobial agents tested in this study appear to have potential for the treatment of multidrug-resistant strains of pneumococci.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3970
Author(s):  
Samson Olaitan Oselusi ◽  
Alan Christoffels ◽  
Samuel Ayodele Egieyeh

The growing antimicrobial resistance (AMR) of pathogenic organisms to currently prescribed drugs has resulted in the failure to treat various infections caused by these superbugs. Therefore, to keep pace with the increasing drug resistance, there is a pressing need for novel antimicrobial agents, especially from non-conventional sources. Several natural products (NPs) have been shown to display promising in vitro activities against multidrug-resistant pathogens. Still, only a few of these compounds have been studied as prospective drug candidates. This may be due to the expensive and time-consuming process of conducting important studies on these compounds. The present review focuses on applying cheminformatics strategies to characterize, prioritize, and optimize NPs to develop new lead compounds against antimicrobial resistance pathogens. Moreover, case studies where these strategies have been used to identify potential drug candidates, including a few selected open-access tools commonly used for these studies, are briefly outlined.


2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Ijeoma N. Okoliegbe ◽  
Karolin Hijazi ◽  
Kim Cooper ◽  
Corinne Ironside ◽  
Ian M. Gould

ABSTRACT Achromobacter spp. are recognized as emerging pathogens in patients with cystic fibrosis (CF). Though recent works have established species-level identification using nrdA sequencing, there is a dearth in knowledge relating to species-level antimicrobial susceptibility patterns and antimicrobial combinations, which hampers the use of optimal antimicrobial combinations for the treatment of chronic infections. The aims of this study were to (i) identify at species-level referred Achromobacter isolates, (ii) describe species-level antimicrobial susceptibility profiles, and (iii) determine the most promising antimicrobial combination for chronic Achromobacter infections. A total of 112 multidrug-resistant (MDR) Achromobacter species isolates from 39 patients were identified using nrdA sequencing. Antimicrobial susceptibility and combination testing were carried out using the Etest method. We detected six species of Achromobacter and found that Achromobacter xylosoxidans was the most prevalent species. Interestingly, sequence analysis showed it was responsible for persistent infection (18/28 patients), followed by Achromobacter ruhlandii (2/3 patients). Piperacillin-tazobactam (70.27%) and co-trimoxazole (69.72%) were the most active antimicrobials. Differences were observed in species-level susceptibility to ceftazidime, carbapenems, ticarcillin-clavulanate, and tetracycline. Antimicrobial combinations with co-trimoxazole or tobramycin demonstrate the best synergy, while co-trimoxazole gave the best susceptibility breakpoint index values. This study enriches the understanding of MDR Achromobacter spp. epidemiology and confirms prevalence and chronic colonization of A. xylosoxidans in CF lungs. It presents in vitro data to support the efficacy of new combinations for use in the treatment of chronic Achromobacter infections.


2005 ◽  
Vol 49 (6) ◽  
pp. 2510-2511 ◽  
Author(s):  
Yunhua Chen ◽  
Elizabeth Garber ◽  
Qiuqu Zhao ◽  
Yigong Ge ◽  
Matthew A. Wikler ◽  
...  

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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