Amoxicillin-clavulanic Acid Resistance Research Articles

Clinical characteristics and bacterial culture in complicated appendicitis at Hue University of Medicine and Pharmacy Hospital

Objectives: To evaluate the clinical, laboratory features, bacterial culture outcomes, and antibiotic susceptibilities of these bacteria in intraoperative samples from patients with perforated appendicitis and to establish whether they influence postoperative outcomes. Materials and methods: A descriptive study was conducted on 68 laparoscopic surgery patients from June 2022 to March 2023 at the Digestive Surgery Department, Hue University of Medicine and Pharmacy Hospital. Results: The male/female ratio is 1.2. The mean age was 37.5 ± 25.7. The mean time of the symptom onset was 37.2 ± 29.1 hours; CRP increased in 86.8% of cases. The average postoperative hospital stay was 6.3 ± 2.2 days; Postoperative complications were observed in 20.6%. Peritoneal fluid samples yielded a positive culture in 58 (85.3%); Gram-negative bacteria were isolated in 89.7%; gram-positive bacteria were isolated in 10.3%; polymicrobial growth was observed in 29.4% of the patients. E. coli in 67.6%, P.aeruginosa in 10.3%, Enterobacter spp. in 8.8%, Klebsiella spp. in 4.4%, Citrobacter spp. in 3%; positive ESBL was present in 17 (37%) of the 46 E. coli strains, ESBL was positivity detected in one of Morganerlla morganii strains. In E. coli, ampicillin resistance was 88.6%, amoxicillin-clavulanic acid resistance was 61.5%, and Trimethoprim-sulfamethoxazole resistance was 65%. Conclusion: It is necessary to choose treatment regimens based on local bacteriology and resistance status to optimize empiric empirical postoperative antibiotic regimens. Key words: perforated appendicitis, ESBL, complications, bacteria culture.

Combined genomic-proteomic approach in the identification of Campylobacter coli amoxicillin-clavulanic acid resistance mechanism in clinical isolates.

Aminopenicillins resistance among Campylobacter jejuni and Campylobacter coli strains is associated with a single mutation in the promoting region of a chromosomal beta-lactamase blaOXA61, allowing its expression. Clavulanic acid is used to restore aminopenicillins activity in case of blaOXA61 expression and has also an inherent antimicrobial activity over Campylobacter spp. Resistance to amoxicillin-clavulanic acid is therefore extremely rare among these species: only 0.1% of all Campylobacter spp. analyzed in the French National Reference Center these last years (2017-2022). Whole genome sequencing with bioinformatic resistance identification combined with mass spectrometry (MS) was used to identify amoxicillin-acid clavulanic resistance mechanism in Campylobacters. A G57T mutation in blaOXA61 promoting region was identified in all C. jejuni and C. coli ampicillin resistant isolates and no mutation in ampicillin susceptible isolates. Interestingly, three C. coli resistant to both ampicillin and amoxicillin-clavulanic acid displayed a supplemental deletion in the promoting region of blaOXA61 beta-lactamase, at position A69. Using MS, a significant difference in the expression of BlaOXA61 was observed between these three isolates and amoxicillin-clavulanic acid susceptible C. coli. A combined genomics/proteomics approach allowed here to identify a rare putative resistance mechanism associated with amoxicillin-clavulanic acid resistance for C. coli.

A Retrospective Study on Amoxicillin Susceptibility in Severe Haemophilus influenzae Pneumonia.

Introduction Treatment of Haemophilus influenzae (Hi) pneumonia is on concern because resistance to amoxicillin is largely diffused. This study describes the evolution of resistance to amoxicillin and amoxicillin/clavulanic acid (AMC) in Hi isolates and characteristics of patients with Hi severe pneumonia. Methods A monocentric retrospective observational study including patients from 2008 to 2017 with severe pneumonia hospitalized in ICU. Evolution of amoxicillin and AMC susceptibility was showed. Characteristics of patients with Hi pneumonia were compared to characteristics of patients with Streptococcus pneumoniae (Sp) pneumonia, as reference. Risk factors for amoxicillin resistance in Hi were investigated. Results Overall, 113 patients with Hi and 132 with Sp pneumonia were included. The percentages of AMC resistance among Hi strains decreased over the years (from 10% in 2008-2009 to 0% in 2016-2017) while resistance to amoxicillin remained stable at 20%. Also, percentages of Sp resistant strains for amoxicillin decreased over years (from 25% to 3%). Patients with Hi pneumonia experienced higher prevalence of bronchitis (18% vs. 8%, p=0.02, chronic obstructive pulmonary disease (43% vs. 30% p=0.03), HAP (18% vs. 7%, p=0.01, ventilator-associated pneumonia (27% vs. 17%, p=0.04, and longer duration of mechanical ventilation (8 days vs. 6 days, p=0.04) than patients with Sp pneumonia. Patients with Sp pneumonia had more frequently local complications than patients with Hi pneumonia (17% vs. 7%, p=0.03). De-escalation of antibiotics was more frequent in patients with Sp than in patients with Hi (67% vs. 53%, p=0.03). No risk factors were associated with amoxicillin resistance among patients with Hi pneumonia. Conclusions Amoxicillin resistance was stable over time, but no risk factors were detected. AMC resistance was extremely low, suggesting that AMC could be used for empiric treatment of Hi pneumonia, as well as other molecules, namely, cephalosporins. Patients with Hi pneumonia had more pulmonary comorbidities and severe diseases than patients with Sp pneumonia.

Characterizing non-linear effects of hospitalisation duration on antimicrobial resistance in respiratory isolates: an analysis of a prospective nationwide surveillance system

ObjectivesOur objective was to systematically study the influence of length of hospital stay on bacterial resistance in relevant respiratory tract isolates. MethodsUsing prospective epidemiological data from the National Swiss Antibiotic Resistance Surveillance System, susceptibility testing results for respiratory isolates retrospectively retrieved from patients hospitalised between 2008 and 2014 were compiled. Generalized additive models were used to illustrate resistance rates relative to hospitalisation duration and to adjust for co-variables. ResultsIn all, 19 622 isolates of six relevant and predominant species were included. Resistance patterns for the predominant species showed a species-specific and antibiotic-resistance-specific profile in function of hospitalisation duration. The oxacillin resistance profile in Staphylococcus aureus isolates was constantly increasing (monophasic). The pattern of resistance to cefepime in Pseudomonas aeruginosa was biphasic with a decreasing resistance rate for the first 5 days of hospitalisation and an increase for days 6–30. A different biphasic pattern occurred in Escherichia coli regarding amoxicillin-clavulanic acid resistance: odds/day increased for the first 7 days of hospitalisation and then remained stable for days 8–30. In the adjusted models epidemiological characteristics such as age, ward type, hospital type and linguistic region were identified as relevant co-variables for the resistance rates. The contribution of these confounders was specific to the individual species/antibiotic resistance models. ConclusionsResistance rates do not follow a dichotomic pattern (early versus late nosocomial) as suggested by current hospital-acquired pneumonia treatment guidelines. Duration of hospitalisation rather appears to have a more complex and non-linear relationship with bacterial resistance in hospital-acquired pneumonia, also depending on host and environmental factors.

Molecular identification of aminoglycoside-modifying enzymes in clinical isolates of Escherichia coli resistant to amoxicillin/clavulanic acid isolated in Spain

The activity of eight aminoglycosides (amikacin, apramycin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin and tobramycin) against a collection of 257 amoxicillin/clavulanic acid (AMC)-resistant Escherichia coli isolates was determined by microdilution. Aminoglycoside resistance rates, the prevalence of aminoglycoside-modifying enzyme (AME) genes, the relationship between AME gene detection and resistance phenotype to aminoglycosides, and the association of AME genes with mechanisms of AMC resistance in E. coli isolates in Spain were investigated. Aminoglycoside-resistant isolates were screened for the presence of genes encoding common AMEs [aac(3)-Ia, aac(3)-IIa, aac(3)-IVa, aac(6′)-Ib, ant(2″)-Ia, ant(4′)-IIa and aph(3′)-Ia] or 16S rRNA methylases (armA, rmtB, rmtC and npmA). In total, 105 isolates (40.9%) were resistant to at least one of the aminoglycosides tested. Amikacin, apramycin and arbekacin showed better activity, with MIC90 values of 2mg/L (arbekacin) and 8mg/L (amikacin and apramycin). Kanamycin presented the highest MIC90 (128mg/L). The most common AME gene was aac(6′)-Ib (36 strains; 34.3%), followed by aph(3′)-Ia (31 strains; 29.5%), ant(2″)-Ia (29 strains; 27.6%) and aac(3)-IIa (23 strains; 21.9%). aac(3)-Ia, aac(3)-IVa, ant(4′)-IIa and the four methylases were not detected. The ant(2″)-Ia gene was usually associated with OXA-1 [21/30; 70%], whilst 23/25 (92%) strains producing CTX-M-15 had the aac(6′)-Ib gene. The most prevalent AME gene was aac(6′)-Ib (18/41; 44%) in nosocomial isolates, whilst ant(2″)-Ia and aph(3′)-Ia genes (20/64; 31%) were more frequent in strains of community origin. In 64.6% isolates the phenotypic profile correlated with the presence of commonly encountered AMEs.

Bactibilia and Antibiotic Resistance in Elective Cholecysctectomy: An Updated Ecologic Survey.

The role of bactibilia as a risk factor for an unfavorable outcome during biliary disease or surgical procedures remains obscure. Our aim was to identify possible risk factors for bactibilia and their possible relations to complications after elective cholecystectomy. As secondary aims, composition and antibiotic resistance patterns were studied. Bile and gallbladder mucosa samples from 358 elective cholecystectomies were collected prospectively between June 2009 and June 2012. Ordinary microbiologic cultures and antibiograms were performed. All pre-operative factors associated with bactibilia were studied by stepwise logistic regression multivariable analysis. The bacteria isolated most frequently from 103 positive cultures were Escherichia coli (21.3%), Enterococcus spp. (14.7%), and Enterobacter spp. (14.7%) with a global amoxicillin-clavulanic acid resistance rate of 53.7%. Age >65 y, male gender, previous instrumentation or disease of the biliary tract, and high American Society of Anesthesiologists score were independent risk factors. No correlation was found between bactibilia and surgical complications. Although the influence of bactibilia in developing surgical complications is limited, its composition and the high rate of resistance can be influential enough to modify antibiotic treatment in biliary tract infections, especially in high-risk patients.

Amoxicillin–clavulanic acid resistance in fecal Enterobacteriaceae from patients with cystic fibrosis and healthy siblings

The present study set out to detect and identify amoxicillin-clavulanic acid (AMC)-resistant Enterobacteriaceae in fecal samples of two patients with cystic fibrosis (CF) and their respective siblings. Fecal Enterobacteriaceae were enumerated onto EMB agar containing amoxicillin (AMX). A total of 173 CF isolates and 41 sibling isolates were grouped into seven Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) clusters and identified through 16S rRNA and rpoB sequence analysis. The fecal microbiota of patients with CF revealed a higher prevalence of AMX resistant Enterobacteriaceae compared to that of their healthy siblings. Whereas all selected isolates of healthy siblings were assigned to Escherichia coli, isolates of patients with CF belonged to Klebsiella oxytoca (58.4%), E. coli (28.3%), Klebsiella variicola (7.5%) or Citrobacter sp. (5.8%). All tested CF isolates showed a high resistance rate to AMX, and a lower level of resistance to the combination with clavulanic acid. In contrast, all tested sibling isolates were susceptible for both AMX and AMC. The higher abundance of AMX resistance in the investigated patients with CF suggests that frequent AMC administration may be one of the major contributing factors in the proliferation of Enterobacteriaceae and the development of resistant strains in the gastrointestinal tract.

Mechanisms of antibiotic resistance in Burkholderia pseudomallei: implications for treatment of melioidosis.

Burkholderia pseudomallei is the etiologic agent of melioidosis. This multifaceted disease is difficult to treat, resulting in high morbidity and mortality. Treatment of B. pseudomallei infections is lengthy and necessitates an intensive phase (parenteral ceftazidime, amoxicillin-clavulanic acid or meropenem) and an eradication phase (oral trimethoprim-sulfamethoxazole). The main resistance mechanisms affecting these antibiotics include enzymatic inactivation, target deletion and efflux from the cell, and are mediated by chromosomally encoded genes. Overproduction and mutations in the class A PenA β-lactamase cause ceftazidime and amoxicillin-clavulanic acid resistance. Deletion of the penicillin binding protein 3 results in ceftazidime resistance. BpeEF-OprC efflux pump expression causes trimethoprim and trimethoprim-sulfamethoxazole resistance. Although resistance is still relatively rare, therapeutic efficacies may be compromised by resistance emergence due to increased use of antibiotics in endemic regions. Novel agents and therapeutic strategies are being tested and, in some instances, show promise as anti-B. pseudomallei infectives.

Antimicrobial Resistance and Spread of Multi Drug Resistant Escherichia coli Isolates Collected from Nine Urology Services in the Euregion Meuse-Rhine

We determined the prevalence and spread of antibiotic resistance and the characteristics of ESBL producing and/or multi drug resistant (MDR) Escherichia coli isolates collected from urine samples from urology services in the Euregio Meuse-Rhine, the border region of the Netherlands (n = 176), Belgium (n = 126) and Germay (n = 119). Significant differences in resistance between the three regions were observed. Amoxicillin-clavulanic acid resistance ranged from 24% in the Netherlands to 39% in Belgium (p = 0.018), from 20% to 40% (p<0.004) for the fluoroquinolones and from 20% to 40% (p = 0.018) for the folate antagonists. Resistance to nitrofurantoin was less than 5%. The prevalence of ESBL producing isolates varied from 2% among the Dutch isolates to 8% among the German ones (p = 0.012) and were mainly CTX-M 15. The prevalence of MDR isolates among the Dutch, German and Belgian isolates was 11%, 17% and 27%, respectively (p< = 0.001 for the Belgian compared with the Dutch isolates). The majority of the MDR and ESBL producing isolates belonged to ST131. This study indicates that most antibiotics used as first choice oral empiric treatment for UTIs (amoxicillin-clavulanic acid, fluoroquinolones and folate antagonists) are not appropriate for this purpose and that MDR strains such as CTX-M producing ST131 have spread in the entire Euregion. Our data stress the importance of ward specific surveillance to optimize empiric treatment. Also, prudent use of antibiotics and further research to alternative agents are warranted.

Predictive value of Escherichia coli susceptibility in strains causing asymptomatic bacteriuria for women with recurrent symptomatic urinary tract infections receiving prophylaxis

A significant proportion of women develop a recurrence following an initial urinary tract infection (UTI). In women with recurrent UTI, the predictive value of asymptomatic bacteriuria (ASB) for the development of a subsequent UTI has not yet been established and it is not known whether information from an asymptomatic sample is useful in guiding antimicrobial therapy. To address these questions, we used data that originated from the ‘Non-antibiotic prophylaxis for recurrent urinary tract infections’ (NAPRUTI) study: two randomized controlled trials on the prevention of recurrent UTI in non-hospitalized premenopausal and postmenopausal women (n = 445). During 15 months of follow-up, no difference was observed in the time to a subsequent UTI between women with and without ASB at baseline (hazard ratio: 1.07, 95% CI 0.80–1.42). The antimicrobial susceptibility and pulsed-field gel-electrophoresis (PFGE) pattern of 50 Escherichia coli strains causing a UTI were compared with those of the ASB strain isolated 1 month previously. The predictive values of the susceptibility pattern of the ASB strain, based on resistance prevalence at baseline, were ≥76%, except in the case of nitrofurantoin-and amoxicillin-clavulanic acid-resistance. Asymptomatic and symptomatic isolates had similar PFGE patterns in 70% (35/50) of the patients. In the present study among women with recurrent UTI receiving prophylaxis, ASB was not predictive for the development of a UTI. However, the susceptibility pattern of E. coli strains isolated in the month before a symptomatic E. coli UTI can be used to make informed choices for empirical antibiotic treatment in this patient population.

Amoxicillin and amoxicillin-clavulanic acid resistance in veterinary medicine - the situation in Europe: a review

In the recent past years, important efforts towards the prudent use of antimicrobials have been made in order to optimize antibacterial use, and maximize therapeutic effect while minimizing the development of resistance. Knowledge on the occurrence of resistance in bacteria could help in improving the clinical success of therapeutic decisions. Since the discovery of amoxicillin, this drug has been extensively used throughout the world in veterinary medicine, alone and also in combination with clavulanic acid. This paper provides information regarding the current situation of resistance to amoxicillin (and amoxicillin-clavulanic acid) in animals in Europe. Most data comes from food-animal species, mainly from several national monitoring programmes of antimicrobial resistance, and information on companion animals is also available.

Increased Amoxicillin–Clavulanic Acid Resistance inEscherichia coliBlood Isolates, Spain

To determine the evolution and trends of amoxicillin–clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006.

Simple and reliable multiplex PCR assay for detection of blaTEM, blaSHV and blaOXA-1 genes in Enterobacteriaceae

Third-generation cephalosporin resistance is often mediated by TEM- and SHV-type β-lactamases in Enterobacteriaceae. TEM-type and OXA-1 enzymes are the major plasmid-borne β-lactamases implicated in amoxicillin–clavulanic acid resistance in Escherichia coli isolates. We have developed a rapid and simple multiplex polymerase chain reaction (PCR) which discriminates bla TEM, bla SHV and bla OXA-1 genes by generating fragments of 516, 392 and 619 bp respectively. Multiplex PCR analysis of 51 amoxicillin–clavulanate resistant E. coli isolates detected bla TEM and bla SHV genes in 45 and two strains, respectively, and only one strain harboured a bla OXA-1 gene. Twenty-three of the 40 cefotaxime-resistant Enterobacteriaceae isolates produced amplicons with a size compatible with the presence of bla TEM (13 strains), bla SHV (six strains) genes or the association of both genes (four strains). These results were verified by colony hybridisation. Therefore, multiplex PCR is a suitable tool for initial rapid screening of bla genes in Enterobacteriaceae.

Discriminatory detection of inhibitor-resistant beta-lactamases in Escherichia coli by single-strand conformation polymorphism-PCR.

Plasmid-mediated mechanisms, comprising TEM hyperproduction, TEM derivative production, and OXA production, lead to amoxicillin-clavulanic acid resistance in enterobacteria. The ability of the single-strand conformation polymorphism (SSCP)-PCR method to differentiate the genes encoding inhibitor-resistant beta-lactamases was evaluated with three bla(TEM) primer pairs. The bla(TEM) genes, which were known to be different on the basis of their nucleotide sequences (bla[TEM-1A], bla[TEM-1B], bla[TEM-2], bla[TEM-30], bla[TEM-32], and bla[TEM-35]), were identified as different by their electrophoretic mobilities. The bla(TEM-33), bla(TEM-34), bla(TEM-36), bla(TEM-37), bla(TEM-38), and bla(TEM-39) genes, whose sequence differences have been established by oligotyping, displayed different SSCP profiles for different fragments, suggesting genetic differences in addition to those defined by oligotyping. Confirmed by sequencing, these additional genetic events concerned silent mutations at certain positions and, notably, a G-->T transversion at position 1 of the -10 consensus sequence in bla(TEM-34), bla(TEM-36), bla(TEM-37), and bla(TEM-39). Applied to eight clinical isolates of Escherichia coli resistant to amoxicillin-clavulanic acid, the SSCP method detected TEM-1 in three strains and TEM-30, TEM-32, and TEM-35 in three other strains, respectively. A novel TEM derivative (TEM-58) was detected in another strain, and the deduced amino acid sequence showed two substitutions: Arg244Ser, which is known to confer amoxicillin-clavulanic acid resistance in TEM-30, and Val261Ile, which has not been described previously. The eighth strain produced an OXA beta-lactamase. Given the discriminatory power and the applicability of SSCP-PCR, this method can be proposed as a means of following the evolution of the frequencies of the different inhibitor-resistant beta-lactamases.