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Antibiotics (Basel, Switzerland) Jun 2024The -independent oxacillin non-susceptible (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure....
Genetic and Phenotypic Changes Related to the Development of -Independent Oxacillin Non-Susceptibility in ST8 Recovered after Antibiotic Therapy in a Patient with Bacteremia.
The -independent oxacillin non-susceptible (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA- isolates recovered during the course of antibiotic treatment from a patient suffering successive episodes of bacteremia. The first isolates (SAMS1, SAMS2, and SAMS3) were susceptible to cefoxitin and oxacillin. The last one (SA2) was susceptible to cefoxitin, resistant to oxacillin, lacked genes, and had reduced susceptibility to teicoplanin. SA2 showed higher β-lactamase activity than SAMS1. However, β-lactamase hyperproduction could not be linked to oxacillin resistance as it was not inhibited by clavulanic acid, and no genetic changes that could account for its hyperproduction were found. Importantly, we hereby report the in vivo acquisition and coexistence of different adaptive mutations in genes associated with peptidoglycan synthesis (, , , , and /), which is possibly related with the development of oxacillin resistance and reduced susceptibility to teicoplanin in SA2. Using three-dimensional models and PBP binding assays, we demonstrated the high contribution of the SA2 PBP2 Ala450Asp mutation to the observed oxacillin resistance phenotype. Our results should be considered as a warning for physicians and microbiologists in the region, as MIONSA detection and treatment represent an important clinical challenge.
PubMed: 38927220
DOI: 10.3390/antibiotics13060554 -
Antibiotics (Basel, Switzerland) Jun 2024, along with various other pathogenic bacteria, may show resistance against a broad spectrum of antibiotics. Evaluating the extent of resistance in harmful...
, along with various other pathogenic bacteria, may show resistance against a broad spectrum of antibiotics. Evaluating the extent of resistance in harmful microorganisms like holds significant importance in crafting novel therapeutic strategies to mitigate or combat the rise of infections stemming from antibiotic-resistant bacteria. The present work aims to investigate the occurrence of antimicrobial resistance among strains in meat products (n = 173), seafood (n = 54), dairy products (n = 19), sauces (n = 2), confectionary products (n = 1), ready-to-eat rice dishes (n = 1), and food-processing environments (n = 19). A total of 269 strains belonging to eight different serovars were tested against 10 antimicrobials. In the classes of antibiotics, most of the strains were resistant antibiotics belonging to the family of β-lactams (92.94%). High proportions of isolates were resistant to oxacillin (88.48%), followed by fosfomycin (85.87%) and flumenique (78.44%). The lowest level of resistance was observed against gentamycin (1.49%). A total of 235 strains (n = 87.36%) showed a profile of multidrug resistance. In conclusion, a high occurrence of resistant and multidrug-resistant strains of was observed among the examined serotypes isolated from different food sources. This understanding enables the adoption of suitable measures to avert contamination and the spread of resistant bacteria via food.
PubMed: 38927191
DOI: 10.3390/antibiotics13060525 -
Microbiology Spectrum Jun 2024Methicillin-resistant (MRSA) bacteremia is a serious clinical challenge with high mortality rates. Antibiotic combination therapy is currently used in cases of...
Methicillin-resistant (MRSA) bacteremia is a serious clinical challenge with high mortality rates. Antibiotic combination therapy is currently used in cases of persistent infection; however, the limited development of new antibiotics will likely increase the need for combination therapy, and better methods are needed for identifying effective combinations for treating persistent bacteremia. To identify pairwise combinations with the most consistent potential for benefit compared to monotherapy with a primary anti-MRSA agent, we conducted a systematic study with an high-throughput methodology. We tested daptomycin and vancomycin each in combination with gentamicin, rifampicin, cefazolin, and oxacillin, and ceftaroline with daptomycin, gentamicin, and rifampicin. Combining cefazolin with daptomycin lowered the daptomycin concentration required to reach 95% growth inhibition (IC) for all isolates tested and lowered daptomycin IC below the sensitivity breakpoint for five out of six isolates that had daptomycin minimum inhibitory concentrations at or above the sensitivity breakpoint. Similarly, vancomycin ICs were decreased when vancomycin was combined with cefazolin for 86.7% of the isolates tested. This was a higher percentage than was achieved by adding any other secondary antibiotic to vancomycin. Adding rifampicin to daptomycin or vancomycin did not always reduce ICs and failed to produce synergistic interaction in any of the isolates tested; the addition of rifampicin to ceftaroline was frequently synergistic and always lowered the amount of ceftaroline required to reach the IC. These analyses rationalize further evaluation of three drug pairs for MRSA bacteremia: daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin.IMPORTANCEBloodstream infections caused by methicillin-resistant (MRSA) have a high mortality rate despite the availability of vancomycin, daptomycin, and newer antibiotics including ceftaroline. With the slow output of the antibiotic pipeline and the serious clinical challenge posed by persistent MRSA infections, better strategies for utilizing combination therapy are becoming increasingly necessary. We demonstrated the value of a systematic high-throughput approach, adapted from prior work testing antibiotic combinations against tuberculosis and other mycobacteria, by using this approach to test antibiotic pairs against a panel of MRSA isolates with diverse patterns of antibiotic susceptibility. We identified three antibiotic pairs-daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin-where the addition of the second antibiotic improved the potency of the first antibiotic across all or most isolates tested. Our results indicate that these pairs warrant further evaluation in the clinical setting.
PubMed: 38916355
DOI: 10.1128/spectrum.00976-24 -
Frontiers in Pediatrics 2024infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on...
BACKGROUND
infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on pediatric patients across Colombia from 2018 to 2021. The aim of this study was to describe the epidemiological and microbiological characteristics of in this patient group.
METHODS
We analyzed isolates from WHONET-reporting centers. An "event" was a positive culture isolation in a previously negative individual after 2 weeks. We studied center characteristics, age distribution, infection type, and antibiotic susceptibilities, comparing methicillin sensitive (MSSA) and resistant (MRSA) isolates.
RESULTS
Isolates from 20 centers across 7 Colombian cities were included. Most centers (80%) served both adults and children, with 55% offering oncology services and 85% having a PICU. We registered 8,157 culture isolations from 5,384 events (3,345 MSSA and 1,961 MRSA) in 4,821 patients, with a median age of 5 years. Blood (26.2%) and skin/soft tissue (18.6%) were the most common infection sources. Most isolates per event remained susceptible to oxacillin (63.2%), clindamycin (94.3%), and TMP-SMX (98.3%). MRSA prevalence varied by city (<0.001), with slightly higher rates observed in exclusively pediatric hospitals. In contrast, the MRSA rate was somewhat lower in centers with Antimicrobial Stewardship Program (ASP). MRSA was predominantly isolated from osteoarticular infections and multiple foci, while MSSA was more frequently associated with recurrent infections compared to MRSA.
CONCLUSIONS
This is the largest study of pediatric infections in Colombia. We found MSSA predominance, but resistance have important regional variations. remains susceptible to other commonly used antibiotics such as TMP-SMX and clindamycin. Ongoing monitoring of infections is vital for understanding their behavior in children. Prospective studies within the Staphylored LATAM are underway for a more comprehensive clinical and genetic characterization.
PubMed: 38895192
DOI: 10.3389/fped.2024.1386310 -
Cureus May 2024Background and objective Urinary tract infections (UTIs) are a common infectious disease affecting people of various ages and genders and are prevalent in different...
The Prevalence of Multidrug-Resistant Uropathogenic Bacterial Profile With Antibiotic Susceptibility Patterns Among the Community and Hospitalized Patients During COVID Waves.
Background and objective Urinary tract infections (UTIs) are a common infectious disease affecting people of various ages and genders and are prevalent in different geographical locations. However, the way Gram-positive and Gram-negative (UTI) germs react to antibiotic treatment varies significantly. The coronavirus disease 2019 (COVID-19) pandemic has increased the frequency of secondary bacterial superinfection, leading to a spike in ongoing recommendations for antibiotic treatment, both therapeutic and preventative. In this study, we aimed to assess uropathogenic bacterial resistance and shed light on how COVID-19 epidemic waves influence the evolution of bacterial resistance. Materials and methods A cross-sectional study was conducted, assessing the different isolates of the uropathogen in all COVID-19 waves by using convenience sampling from August 2020 till the end of 2023. The VITEK-2 compact system employing industry-standard bacteriological tests to identify the bacteria and confirm their antibiotic susceptibility was utilized. Results Of the total 3877 patients, 381 (9.8%) and 3483 (89.8%) had positive and negative microbial growth, respectively. Of the 381 (9.8%) positive cases, 130 (34%) were male and 251 (65%) were female; 138 (43.3%) patients in the age range of 15-40 years developed sporadic UTIs attributed to Gram-negative bacteria. Alternatively, patients over 40 years had the highest prevalence rate (n = 180, 56.6%). The most common strains of Gram-negative and Gram-positive bacteria were and with278 (88.8%) and 13 (20.9%) cases respectively. People with Gram-negative bacteria who were not hospitalized were very resistant to trimethoprim/sulfamethoxazole (n = 219, 69.1%), cefotaxime (n = 193, 60.9%), ampicillin (n = 192, 60.6%), and amoxicillin/clavulanic acid (176, 55.5%). While high sensitivity to meropenem (n = 14, 4.4%) and imipenem (n = 13, 4.1%) was observed, hospitalized individuals had higher levels of resistance and great sensitivity to the same antibiotics. S. . were commonly present. Hospitalized patients were less sensitive to benzylpenicillin, ampicillin, and oxacillin, and there was a big rise in resistance to cefoxitin in the community. Conclusions In this study, Gram-negative germs among females were predominantly observed with extremely high multi-drug resistance (MDR). The most effective antibiotics against Gram-positive germs included linezolid, vancomycin, and nitrofurantin, while those against Gram-negative bacteria were meropenem and amikacin. Clinicians should be regularly updated and informed about antibiotic selection through routine monitoring of uropathogenic bacteria's susceptibility. Moreover, we recommend changes to the local antibiotic policy regarding the selection of UTIs; further multicentric and high-volume studies are required to gain deeper insights into the topic.
PubMed: 38894805
DOI: 10.7759/cureus.60613 -
Medicine Jun 2024In Algeria, the issue of antibiotic resistance is on the rise, being the Staphylococcus aureus infection as a significant concern of hospital-acquired infections. The... (Observational Study)
Observational Study
In Algeria, the issue of antibiotic resistance is on the rise, being the Staphylococcus aureus infection as a significant concern of hospital-acquired infections. The emergence of antibiotic resistance in this bacterium poses a worldwide challenge. The aim of this study aims to establish the incidence of S aureus strains in Algeria as well as identify phenotypic and genotypic resistance based on the "mecA" and "nuc" genes. From 2014 to 2017, a total of 185 S aureus strains were isolated from patients at a hospital in the city of Rouïba, Algiers the number of isolates was slightly higher in males at 58.06% compared to females at 41.94%, resulting in a sex ratio of 1.38. the Oxacillin and Cefoxitin DD test (1 μg oxacillin disk and 30 μg cefoxitin disk) identified 42 strains as resistant. The results indicated high resistance to lactam antibiotics, with penicillin having a 100% resistance rate. There was also significant resistance to oxacillin (51.25%) and cefoxitin (50%). This resistance was frequently associated with resistance to other antibiotic classes, such as aminoglycosides (50%) and Macrolides (28.29%). To confirm methicillin-resistant characteristics, a polymerase chain reaction (PCR) multiplex was conducted on 10 isolates (6 SARM; 4 MSSA) on a phenotypic level. Three isolates tested positive for "mecA," while 7 were negative. All strains carry the nuc gene, which is specific to S aureus. In Algeria, the incidence of S aureus resistance is slightly lower compared to other countries, but it is increasing over time. It is now more crucial than ever to restrict the proliferation of multidrug-resistant strains and reduce undue antibiotic prescriptions. To achieve this, it is vital to keep updated on the epidemiology of this bacterium and its antibiotic susceptibility. This will enable the formulation of appropriate preventive control measures to manage its progression.
Topics: Humans; Anti-Bacterial Agents; Female; Male; Staphylococcus aureus; Staphylococcal Infections; Algeria; Prevalence; Microbial Sensitivity Tests; Bacterial Proteins; Oxacillin; Adult; Penicillin-Binding Proteins; Cefoxitin; Middle Aged; Micrococcal Nuclease; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Methicillin-Resistant Staphylococcus aureus
PubMed: 38875387
DOI: 10.1097/MD.0000000000038562 -
BioRxiv : the Preprint Server For... May 2024Methicillin-resistant (MRSA), a Gram-positive bacterial pathogen, continues to pose a serious threat to the current public health system in our society. The high level...
Methicillin-resistant (MRSA), a Gram-positive bacterial pathogen, continues to pose a serious threat to the current public health system in our society. The high level of resistance to β-lactam antibiotics in MRSA is attributed to the expression of penicillin-binding protein 2a (PBP2a), which catalyzes cell wall cross-linking. According to numerous research reports, the activity of the PBP2a protein is known to be regulated by an allosteric site distinct from the active site where cell wall cross-linking occurs. Here, we conducted a screening of 113 compounds containing a 1,3,4-oxadiazole core to design new covalent inhibitors targeting the allosteric site of PBP2a and establish their structural-activity relationship. The stereochemically selective synthesis of sulfonyl oxadiazole compounds identified in the initial screening resulted in a maximum eightfold enhancement in cell inhibition activity. The sulfonyl oxadiazole-based compounds formulated as PEG-based ointments, with low toxicity test results on human cells (CC : >78μM), demonstrated potent antimicrobial effects not only in a mouse skin wound infection model but also against oxacillin-resistant clinical isolate MRSA (IC ≈ 1μM), as evidenced by the results. Furthermore, additional studies utilizing LC-MS/MS and in-silico approaches clearly support the allosteric site covalent binding mechanism through the nucleophilic aromatic substitution (S Ar) reaction, as well as its association with the closure of the major active site of PBP2a.
PubMed: 38853829
DOI: 10.1101/2024.05.29.596450 -
Japanese Journal of Infectious Diseases May 2024Biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative Staphylococci (MR-CoNS) are a clinical challenge for the treatment of...
Biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative Staphylococci (MR-CoNS) are a clinical challenge for the treatment of healthcare-associated infections. As alternative antimicrobial options are needed, we aimed to determine the effect of curcumin-chitosan magnetic nanoparticles on the biofilm of staphylococcal clinical isolates. MRSA and CoNS clinical isolates were identified by MALDI-TOF mass spectrometry. Antimicrobial susceptibility testing was performed by broth microdilution. Nanoparticles were synthesized by co-precipitation of magnetic nanoparticles (MNP) and encapsulation by ionotropic gelation of curcumin (Cur) and chitosan (Chi). Biofilm inhibition and eradication by nanoparticles with and without the addition of oxacillin was assessed on staphylococcal strains. Cur-Chi-MNP showed antimicrobial activity on planktonic cells of MRSA and MR-CoNS strains and inhibited biofilm of MRSA. The addition of OXA to Cur-Chi-MNP increased biofilm inhibition and eradication activity against all Staphylococci strains (p=0.0007); higher biofilm activity was observed in early biofilm stages. Cur-Chi-MNP showed antimicrobial and biofilm inhibition activity against S. aureus. The addition of OXA increased biofilm inhibition and eradication activity against all Staphylococci strains. A combination treatment of Cur-Chi-MNP and OXA could be potentially used to treat staphylococcal biofilm-associated infections in its early stages before the establishment of biofilm bacterial cells.
PubMed: 38825455
DOI: 10.7883/yoken.JJID.2024.034 -
Journal of Dairy Science May 2024The objective of this study was to analyze the in vitro antimicrobial resistance (AMR) of Streptococcus (Sc.) dysgalactiae, Sc. agalactiae, and Sc. canis over a 10-year...
Antimicrobial resistance of Streptococcus dysgalactiae, Streptococcus agalactiae, and Streptococcus canis in quarter milk samples from Bavaria, Southern Germany, between 2012 and 2022.
The objective of this study was to analyze the in vitro antimicrobial resistance (AMR) of Streptococcus (Sc.) dysgalactiae, Sc. agalactiae, and Sc. canis over a 10-year period from 2012 to 2022 against the most commonly used antimicrobial agents. For this purpose, all quarter milk samples (QMS) submitted to the milk laboratory of the Bavarian Animal Health Service (TGD) were analyzed. Each QMS was tested using the California Mastitis Test (CMT) and categorized as negative (N), subclinical (S), or clinical (C) mastitis if the milk character was abnormal. Samples with Sc. dysgalactiae, Sc. agalactiae, or Sc. canis were included and a subset of isolates were further tested for in vitro antimicrobial resistance by breakpoint analysis with broth microdilution. Sc. dysgalactiae (61%, n = 65,750) was the most abundant pathogen among those 3 species, followed by Sc. agalactiae (28%, n = 30,486), and Sc. canis (11%, n = 11,336). All 3 species showed the highest resistance to the same 4 antimicrobial agents: erythromycin, marbofloxacin, pirlimycin, and cefalexin/kanamycin with varying degrees of resistance. Throughout the study period, Sc. dysgalactiae, Sc. agalactiae, and Sc. canis were largely susceptible to the remaining antimicrobial agents tested (penicillin, amoxicillin-clavulanate, oxacillin, cefazolin, cefoperazone, cefquinome). Only less than 14% of isolates of Sc. dysgalactiae and Sc. canis were resistant against any of the antimicrobials tested. Sc. agalactiae was the species with the highest percentage of resistant isolates. While the percentage of resistant isolates from Sc. canis and Sc. dysgalactiae decreased, the percentage of resistant Sc. agalactiae isolates increased since 2017. In summary, most isolates were not resistant to the most commonly used antimicrobial agents for mastitis therapy, including β-lactam antibiotics and penicillin should remain the first-choice therapy against streptococcal mastitis.
PubMed: 38825124
DOI: 10.3168/jds.2023-24555 -
Journal of Chromatography. B,... Jul 2024After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is...
After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is removed, a debridement is performed and a new or temporary spacer is placed. Additionally, patients are treated with antibiotics during and after the surgery. Adequate exposure of the administered antibiotic to the pathogen is of crucial importance during the treatment of any infection. Inadequately low concentrations are associated with an increase in antibiotic resistance, antibiotic related side effects, treatment failures and prolonged infections. While high concentrations may lead to serious adverse events and potential lasting damage. Despite the importance of optimal dosing, there is a lack of knowledge with respect to the correlation between the plasma concentrations and target site concentrations of the antibiotics. Two of the commonly administered antimicrobial agents during the arthroplasty exchange are cefuroxime and flucloxacillin. Therefore, an accurate, specific, and sensitive quantification method is required in order to assess pharmacokinetics of cefuroxime and flucloxacillin in synovial tissue and bone. The aim of this study is to develop and validate a quantification method for the measurement of cefuroxime and flucloxacillin in human synovial tissue and bone using the UPC-MS/MS conform Food and Drug Administration guidelines. The method was found linear for both compounds in both matrices (r > 0.990) from 1 µg/g to 20 µg/g, except for cefuroxime in bone, which was validated from 1 µg/g to 15 µg/g. We developed and validated a quantification method for cefuroxime and flucloxacillin in synovial tissue and bone using a simple sample preparation and a short analysis run time of 5.0 min, which has been already successfully applied in a clinical study. To our knowledge, no methods have been described earlier for the simultaneous quantification of cefuroxime and flucloxacillin in synovial tissue and bone.
Topics: Humans; Tandem Mass Spectrometry; Cefuroxime; Chromatography, High Pressure Liquid; Linear Models; Reproducibility of Results; Floxacillin; Anti-Bacterial Agents; Bone and Bones; Synovial Membrane; Limit of Detection
PubMed: 38815354
DOI: 10.1016/j.jchromb.2024.124169