Geographical and Ecological Analysis of Resistance, Coresistance, and Coupled Resistance to Antimicrobials in Respiratory Pathogenic Bacteria in Spain

ABSTRACT A multicenter susceptibility surveillance (the S.A.U.C.E. project) including 2,721 Streptococcus pneumoniae, 3,174 Streptococcus pyogenes, and 2,645 Haemophilus influenzae consecutive isolates was carried out in 25 hospitals all over Spain from November 2001 to October 2002 to evaluate the current epidemiology of resistance of the main bacteria involved in community-acquired respiratory tract infections. Susceptibility testing was performed in a single centralized laboratory by a broth microdilution method. The prevalence of resistant S. pneumoniae strains was 0.4% for cefotaxime, 4.4% for amoxicillin and amoxicillin-clavulanic acid, 25.6% for cefuroxime-axetil, 34.5% for erythromycin, clarithromycin, and azithromycin, and 36.0% for cefaclor. Phenotypes of resistance to erythromycin were MLSB (macrolide-lincosamide-streptogramin B) in 89.9% (gene ermB) and M (macrolide) in 9.7% of cases (gene mefA). No strain harbored both genes simultaneously. Serotypes 19, 6, 23, 14, and 3 were the most prevalent, accounting for 54.6% of the total isolates. Resistance to macrolides seems to be the most alarming point, since among penicillin-susceptible isolates it reached 15.1% compared to 55.8% among penicillin-resistant strains. Geographically, a number of regions had rates of erythromycin resistance above 40% (even higher in children). Resistance to erythromycin was also high in S. pyogenes isolates: mean regional 33.2%, beta-lactamase-producing H. influenzae were 20%, whereas 4.4% had a beta-lactamase-negative, ampicillin-resistant phenotype. We highlight the importance of different geographical frequencies of coresistance (associations of resistance to different drugs within the same species) and coupled resistance (association of resistance between different species) probably resulting from different local coselective events.

Download Full-text

Cefuroxime Axetil

Drug Intelligence & Clinical Pharmacy ◽

10.1177/106002808802200901 ◽

1988 ◽

Vol 22 (9) ◽

pp. 651-658 ◽

Cited By ~ 6

Author(s):

Michael A. Marx ◽

William K. Fant

Keyword(s):

Respiratory Infections ◽

Acute Otitis Media ◽

Cefuroxime Axetil ◽

Moderate Activity ◽

Beta Lactamase ◽

Amoxicillin Clavulanic Acid ◽

Gram Negative Organisms ◽

Tract Infections ◽

Branhamella Catarrhalis

Cefuroxime axetil is a orally active prodrug formulation of cefuroxime, which upon absorption undergoes immediate deesterification to free cefuroxime. Cefuroxime axetil offers an in vitro antibacterial spectrum against many gram-positive and some gram-negative organisms. Its beta-lactamase stability makes it useful in treating a variety of infections caused by beta-lactamase-producing strains of Haemophilus influenzae, Branhamella catarrhalis, and Staphylococcus aureus. Cefuroxime axetil has good activity against the Enterobacteriaceae and moderate activity against non-Bacteroides fragilis anaerobes. Clinical studies suggest it is at least as effective as ampicillin, amoxicillin, amoxicillin/clavulanic acid, penicillin V, or cefaclor in the treatment of uncomplicated urinary tract infections, acute otitis media, upper respiratory infections, skin and soft tissue infections, and uncomplicated gonorrhea.

Download Full-text

SENSITIVITY AND RESISTANCE TO ANTIMICROBIAL AGENTS ESBL-PRODUCING AND NOT PRODUCING ESBL STRAINS OF E. COLI IN PATIENTS WITH URINARY TRACT INFECTION

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2019-64-2-104-110 ◽

2019 ◽

Vol 64 (2) ◽

pp. 104-110

Author(s):

N. I. Dimitrova ◽

T. D. Gasretova ◽

E. L. Alutina ◽

G. G. Kharseeva

Keyword(s):

Urinary Tract ◽

Antimicrobial Agents ◽

Beta Lactamase ◽

Test Results ◽

Beta Lactams ◽

Esbl Production ◽

E Coli ◽

Amoxicillin Clavulanate ◽

Resistant Strains ◽

Tract Infections

As a result of the conducted researches it is shown that 44.1% of urinary tract infections (UTIS) caused by E. coli are accounted for by producers of beta-lactamase of the extended spectrum of action (ESBL). Associated resistance to fluoroquinolones and co-trimoxazole was found in 93.3% of BLRS-producing E. coli strains. All studied strains regardless of ESBL production were sensitive to imipenem, the majority showed sensitivity to ertapenem, gentamicin and resistance to doxycycline. Not producing ESBL strains of E. coli were sensitive to fosfomycin. Comparison of data obtained during testing of isolated cultures on ESBL, study of their sensitivity and resistance to beta-lactams (amoxicillin/clavulanate, ceftazidime, ceftriaxone, cefotaxime, imipenem) indicates the need to test isolates for AmpC products. To this end, during the screening test for ESBL and the method of «double disks», along with cephalosporins of III generation, it is necessary to use a phenotypic test for sensitivity to cefepime. The use of test results of E. coli isolates isolated from patients with UTIS for the production of ESBL, ampC enzymes, carbapenemase and sensitivity to AMP will improve the effectiveness of antimicrobial therapy and will help to curb the formation and spread of antimicrobial-resistant strains.

Download Full-text

Variation in erythromycin and clindamycin susceptibilities of Streptococcus pneumoniae by four test methods.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.1.129 ◽

1997 ◽

Vol 41 (1) ◽

pp. 129-134 ◽

Cited By ~ 39

Author(s):

E L Fasola ◽

S Bajaksouzian ◽

P C Appelbaum ◽

M R Jacobs

Keyword(s):

Streptococcus Pneumoniae ◽

Susceptibility Testing ◽

Ambient Air ◽

Test Methods ◽

Disk Diffusion ◽

Broth Microdilution ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Agar Dilution ◽

Resistant Strains

Susceptibilities of 124 strains of Streptococcus pneumoniae to erythromycin and clindamycin were determined by the National Committee for the Clinical Laboratory Standards (NCCLS) broth microdilution method, with incubation for 20 to 24 h in ambient air and with modifications of this method by incubation for up to 48 h in air and CO2. Strains were also tested by agar dilution, E-test, and disk diffusion; good correlation was obtained with these methods, with clear separation into bimodal populations of susceptible and resistant stains. The broth microdilution method, however, using incubation in air for 24 h (NCCLS method), misclassified 4 of 92 erythromycin-resistant strains (1 as susceptible and 3 as intermediate) and 25 of 58 clindamycin-resistant strains (all as susceptible). With the exception of one strain with clindamycin, susceptible and resistant strains were correctly classified by the microdilution method with incubation in CO2 for 24 h or in ambient air for 48 h. Disk diffusion, agar dilution, and E-test methods with incubation in 5% CO2 are therefore reliable methods for susceptibility testing of pneumococci against these agents. However, the NCCLS microdilution method, which specifies incubation for 20 to 24 h in ambient air, produced significant very major errors (43%) clindamycin. Modification of the microdilution method by incubation in 5% CO2 or by extension of incubation time in ambient air to 48 h corrected these errors. Disk diffusion, however, was shown to be a simple, convenient, and reliable method for susceptibility testing of pneumococci to erythromycin and clindamycin and is suggested as the method of choice for these agents.

Download Full-text

Inhibitory Effects and Killing Kinetics of Lactic Acid Rice Gel Against Pathogenic Bacteria Causing Bovine Mastitis

Scientia Pharmaceutica ◽

10.3390/scipharm86030029 ◽

2018 ◽

Vol 86 (3) ◽

pp. 29 ◽

Cited By ~ 7

Author(s):

Rinrada Chotigarpa ◽

Kannika Na Lampang ◽

Surachai Pikulkaew ◽

Siriporn Okonogi ◽

Kittisak Ajariyakhajorn ◽

...

Keyword(s):

Lactic Acid ◽

Pathogenic Bacteria ◽

Bovine Mastitis ◽

Kinetic Studies ◽

Rolling Ball ◽

Microdilution Method ◽

Skin Bacteria ◽

Alternative Product ◽

Broth Microdilution Method ◽

Kinetics Of

Staphylococcus aureus and S. epidermidis are the major teat skin bacteria and lead to severe bovine mastitis. Teat antiseptic is an important tool for controlling intramammary infection. The antibacterial activity of lactic acid (LA) against one reference strain of S. aureus ATCC 25923 and two field strains including S. aureus and S. epidermidis was investigated using the broth microdilution method. Its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 0.5% for strains belonging to both species. An antiseptic preparation containing 5% LA with modified rice gel (LA-RG) was successfully prepared. Rheological behavior of LA-RG was found to be a pseudoplastic flow with thixotropy with viscosity of approximately 0.007 Pas. LA-RG exhibited a sufficient adhesive property in the rolling ball test with a length of 9.67 ± 0.04 cm. Killing kinetic studies of LA-RG showed that the killing rate of LA-RG was significantly faster than that of LA. After 32 min of exposure to LA-RG, approximately 86% and 60% of S. aureus and S. epidermidis were reduced, respectively. Abnormal bacterial cell surface after exposure to LA-RG was observed by scanning electron microscopy. It is concluded that LA-RG is a promising preparation as an alternative product for preventing mastitis in dairy cattle.

Download Full-text

Synthesis andIn VitroEvaluation of New Thiosemicarbazone Derivatives as Potential Antimicrobial Agents

Journal of Chemistry ◽

10.1155/2016/1692540 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Zafer Asım Kaplancıklı ◽

Mehlika Dilek Altıntop ◽

Belgin Sever ◽

Zerrin Cantürk ◽

Ahmet Özdemir

Keyword(s):

Antibacterial Activity ◽

Pathogenic Bacteria ◽

Antimicrobial Agents ◽

Aromatic Aldehydes ◽

Antitubercular Activity ◽

Alamar Blue Assay ◽

Alamar Blue ◽

Inhibitory Effects ◽

Microdilution Method ◽

Broth Microdilution Method

In an effort to develop potent antimicrobial agents, new thiosemicarbazone derivatives were synthesizedviathe reaction of 4-[4-(trifluoromethyl)phenyl]thiosemicarbazide with aromatic aldehydes. The compounds were evaluated for their inhibitory effects on pathogenic bacteria and yeasts using the CLSI broth microdilution method. Microplate Alamar Blue Assay was also carried out to determine the antimycobacterial activities of the compounds againstMycobacterium tuberculosisH37Rv. Among these derivatives, compounds5and11were more effective againstEnterococcus faecalis(ATCC 29212) than chloramphenicol, whereas compounds1,2, and12and chloramphenicol showed the same level of antibacterial activity againstE. faecalis. Moreover, compound2and chloramphenicol exhibited the same level of antibacterial activity againstStaphylococcus aureus. On the other hand, the most potent anticandidal derivatives were found as compounds2and5. These derivatives and ketoconazole exhibited the same level of antifungal activity againstCandida glabrata. According to the Microplate Alamar Blue Assay, the tested compounds showed weak to moderate antitubercular activity.

Download Full-text

In vitro activity of imipenem/relebactam against Gram-negative clinical isolates in two Spanish tertiary hospitals

Revista Española de Quimioterapia ◽

10.37201/req/102.2021 ◽

2021 ◽

Author(s):

Marina Peñuelas ◽

◽

Cristina García-Salguero ◽

Melania Iñigo ◽

Jose Manuel Viñuela-Prieto ◽

...

Keyword(s):

High Activity ◽

Clinical Isolates ◽

Beta Lactamase ◽

Extended Spectrum Beta Lactamase ◽

Klebsiella Pneumoniae Carbapenemase ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Class B ◽

Tertiary Hospitals

Objetive. The aim of this study was to analyze the activity of the imipenem-relebactam combination (IMI/REL) against a collection of multidrug-resist Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii clinical isolates. Material and methods. The study was conducted in two tertiary hospitals in Spain and included 192 clinical isolates of these 3 genera (139 resistant and 53 susceptible to IMI). The MICs for IMI with and without REL (at a fixed concentration of 4 mg/L) were determined by a standard broth microdilution method according to international recommendations. Results. All IMI-susceptible E. coli strains were also susceptible to IMI/REL. Enterobacterales resistant to IMI due to the production of carbapenemases, the MIC50 and MIC90 decreased from 64/256 with IMI to 8/64 mg/L with IMI/REL. This high activity was principally detected among isolates with KPC enzymes. Enterobacterales with class B carbapenemases, P. aeruginosa carrying VIM carbapenemase and A. baumannii strains showed no changes on IMI MIC50 or MIC90 after adding REL. Among P. aeruginosa strains without carbapenemase the MIC for IMI/REL was reduced between 1 to 5 dilutions. Conclusions. IMI/REL showed high activity against the strains that carry Klebsiella pneumoniae carbapenemase (KPC) and against carbapenem-resistant P. aeruginosa unrelated to the VIM enzyme, mainly AmpC beta lactamase associated with impermeability. Against strains carrying oxacillinase 48 (OXA-48) associated with extended-spectrum beta-lactamase (ESBL), IMI/REL presented activity only slightly better than IMI and had no beneficial effect superior to IMI against A. baumannii.

Download Full-text

656. Sulbactam-Durlobactam MIC Determination: Comparative Evaluation of the New ETEST® SUD to the CLSI 2021 Broth Microdilution Method

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.853 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S430-S430

Author(s):

Veronique Sauvonnet ◽

Elodie Escoffier ◽

Christine Franceschi ◽

Diane Halimi ◽

Roland Martelin ◽

...

Keyword(s):

Reference Method ◽

Multidrug Resistant ◽

Error Rates ◽

Broth Microdilution ◽

Microdilution Method ◽

Mueller Hinton ◽

Broth Microdilution Method ◽

Lactam Antibiotic ◽

Visible Growth ◽

Resistant Strains

Abstract Background Species belonging to the Acinetobacter baumannii-calcoaceticus (ABC) complex, such as A. baumannii, A. pittii and A. nosocomialis, are a major cause of hospital acquired infections and outbreaks with increasing occurrence of multidrug-resistance. Sulbactam-durlobactam (SUD), a combination of one active β-lactam antibiotic (sulbactam) with a new β-lactamase inhibitor (durlobactam), is currently being tested in a phase 3 clinical trial by Entasis Therapeutics for the treatment of serious infections caused by ABC, including multidrug-resistant strains. At the same time, an ETEST® SUD (sulbactam-durlobactam - MIC range 0.004/4-64/4 µg/mL) has been developed and calibrated versus the broth microdilution reference method (BMD) as described by the Clinical and Laboratory Standards Institute (CLSI). This test is intended to determine the MIC of sulbactam-durlobactam for species of the ABC complex. The aim of this study was to perform a first comparative study of ETEST SUD with the CLSI BMD method on a panel of 263 isolates. Methods The panel consisted of 204 A. baumannii, 29 A. pittii, 30 A. nosocomialis, including 24 SUD-resistant strains, and one CLSI QC strain. BMD was performed using the 2021 CLSI guidelines. ETEST SUD was evaluated using the standard ETEST procedure for Acinetobacter spp. (inoculum 0.5 McFarland, Mueller Hinton medium, incubation at 35°C for 20-24h). For each method, the MIC was read at complete inhibition of visible growth. To determine category agreement (CA) and error rates, the sulbactam-durlobactam provisional breakpoint of 4 µg/mL was applied. Results The QC strain MICs were in the expected range with reproducible results. The essential MIC agreement [EA, ±1 dilution] was 97.7% without any tendency to over- or underestimate the MIC when compared to BMD. The CA was 98.5%. Two Very Major Errors, both within the EA, and two Major Errors, one within the EA, were observed. Conclusion In this study, the ETEST SUD was found to be equivalent to the CLSI reference method. MIC end points were easy to read. With a 15-dilution range and simplicity of use, ETEST SUD could represent a valuable tool for MIC determination and could be an alternative to BMD. For Research Use Only. The performance characteristics of this product have not been established yet. Disclosures All Authors: No reported disclosures

Download Full-text

Resistance to Beta-Lactams in Enterobacteriaceae: Distribution of Phenotypes Related to Beta-Lactamase Production

Journal of International Medical Research ◽

10.1177/030006058601400405 ◽

1986 ◽

Vol 14 (4) ◽

pp. 193-199 ◽

Cited By ~ 1

Author(s):

D Sirot ◽

J Sirot ◽

P Saulnier ◽

B Joly ◽

M Chanal ◽

...

Keyword(s):

Serratia Marcescens ◽

Clavulanic Acid ◽

Enterobacter Cloacae ◽

Beta Lactamase ◽

Proteus Vulgaris ◽

Beta Lactams ◽

Beta Lactamases ◽

Amoxicillin Clavulanic Acid ◽

Resistant Strains ◽

Disk Method

Phenotypes of susceptibility to amoxycillin (Amo), ticarcillin (Tic), cephalothin (Ctn) were determined in 1366 isolates of Enterobacteriaceae by disk method and beta-lactamases were identified in 243 strains belonging to different phenotypes of amoxycillin-resistant strains. AmoR TicR Ctns strains (25%) were penicillinase producers and all of them were susceptible to the combination amoxicillin/clavulanic acid (Amo/CA) and ticarcillin/clavulanic acid (Tic/CA). AmoI/R Tics CtnR strains (12%) were cephalosporinase producers and resistance to Amo/CA was observed, except for Proteus vulgaris. AmoR TicR CtnR strains (18%) often produced two beta-lactamases (penicillinase and cephalosporinase) and they were resistant to Amo/CA; in this group, susceptibility to Tic/CA depends on the nature and the amount of the beta-lactamase produced, except for Serratia marcescens for which antibiotic resistance is probably due to other mechanisms. Tic/CA resistance was mainly found in Serratia marcescens (41%) and Enterobacter cloacae (36%).

Download Full-text

1589. Ceftolozane–Tazobactam Activity Against Difficult-to-Treat Resistance in Pseudomonas aeruginosa from Bloodstream Infections in US Hospitals

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1453 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S580-S580

Author(s):

Dee Shortridge ◽

S J Ryan Arends ◽

Leonard R Duncan ◽

Jennifer M Streit ◽

Robert K Flamm

Keyword(s):

Pseudomonas Aeruginosa ◽

Bloodstream Infections ◽

The United States ◽

Multidrug Resistant ◽

First Line ◽

Microdilution Method ◽

Drug Classes ◽

Broth Microdilution Method ◽

Tract Infections ◽

Abdominal Infections

Abstract Background Infections caused by Pseudomonas aeruginosa (PSA) resistant to first-line agents are difficult to treat and require using more toxic antimicrobials, such as amikacin (AMK) and colistin (COL). Kadri et al. recently described the category of difficult-to-treat resistance (DTR) as intermediate or resistant to all tested first-line agents (fluoroquinolones, carbapenems, and extended-spectrum cephalosporins). Ceftolozane–tazobactam (C-T) is an antibacterial combination of an antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T has been approved in >60 countries to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections. The filing is in progress for treatment of hospital-acquired pneumonia, including ventilator-associated pneumonia. The Program to Assess Ceftolozane–Tazobactam Susceptibility (PACTS) monitors gram-negative (GN) isolates resistant to C-T worldwide. In this study, the activity of C-T and comparators against PSA bloodstream isolates that are DTR, multidrug-resistant (MDR), or extensively drug-resistant (XDR) were analyzed. Methods A total of 922 PSA isolates from BSI were collected between 2011 and 2018 from 35 PACTS hospitals in the United States. Isolates were tested for C-T susceptibility (S) by the CLSI broth microdilution method. Other antibiotics tested included cefepime (FEP), ceftazidime (CAZ), ciprofloxacin, levofloxacin (LEV), doripenem, imipenem, meropenem (MEM), piperacillin–tazobactam (PIP-TAZ), AMK and COL. Antibiotic-resistant phenotypes analyzed using CLSI (2019) breakpoints included MDR (nonsusceptible to ≥ 1 agent in ≥ 3 drug classes), XDR (susceptible to ≤ 1 agent in ≤ 2 drug classes), or DTR. Results The percent of DTR isolates was 4.8% when compared with 15.2% MDR and 9.3% XDR. The %S for C-T and other first- and second-line agents are shown in the table for each phenotype. Conclusion C-T demonstrated 97.1%S overall for BSI isolates, similar to AMK (97.8%) and COL (99.5%). C-T had better coverage than first-line drugs against MDR (81.4%) and XDR (72.1%), and 50% for the DTR isolates, which represented only 4.8% of isolates. Only AMK and COL had > 75%S for DTR isolates. Disclosures All authors: No reported disclosures.

Download Full-text

Tentative epidemiologic cut-off value and resistant characteristic detection of apramycin against Escherichia coli from chickens

FEMS Microbiology Letters ◽

10.1093/femsle/fnz196 ◽

2019 ◽

Vol 366 (16) ◽

Cited By ~ 2

Author(s):

Erjie Tian ◽

Ishfaq Muhammad ◽

Wanjun Hu ◽

Zhiyong Wu ◽

Rui Li ◽

...

Keyword(s):

Escherichia Coli ◽

Drug Resistance ◽

Multiple Drug Resistance ◽

Aminoglycoside Antibiotic ◽

Multiple Drug ◽

Broth Microdilution ◽

E Coli ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Resistant Strains

ABSTRACT Escherichia coli are important foodborne zoonotic pathogens. Apramycin is a key aminoglycoside antibiotic used by veterinarians against E. coli. This study was conducted to establish the epidemiological cut-off value (ECV) and resistant characteristics of apramycin against E. coli. In this study, 1412 clinical isolates of E. coli from chickens in China were characterized. Minimum inhibitory concentrations (MICs) of apramycin were assessed by broth microdilution method. MIC50 and MIC90 for apramycin against E. coli (0.5–256 µg/mL) were 8 and 16 µg/mL, respectively. In this study, the tentative ECV was determined to be 16 µg/mL by the statistical method and 32 µg/mL by ECOFFinder software. Besides, the percentages of aac(3)-IV positive strains ascended with the increase of MIC values of apramycin, and the gene npmA was detected in strains with higher MICs. Sixteen apramycin highly resistant strains displayed multiple drug resistance (100%) to amoxicillin, ampicillin, gentamicin, doxycycline, tetracycline, trimethoprim and florfenicol, while most of them were susceptible to amikacin and spectinomycin. In summary, the tentative ECV of apramycin against E. coli was recommended to be 16 µg/mL.

Download Full-text