scholarly journals Occurrence of Antimicrobial Resistance Genes in the Oral Cavity of Cats with Chronic Gingivostomatitis

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3589
Author(s):  
Wayne Tsang ◽  
Annika Linde ◽  
Janina A. Krumbeck ◽  
Guangxi Wu ◽  
Young J. Kim ◽  
...  
Keyword(s):  
Fungal Species ◽  
Human Medicine ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Gene Frequencies ◽  
Immune Mediated ◽  
Antimicrobial Resistance Genes ◽  
Tissue Surfaces ◽  
Oral Tissue ◽  
Microbial Dna

Feline chronic gingivostomatitis (FCGS) is a severe immune-mediated inflammatory disease with concurrent oral dysbiosis (bacterial and fungal). Broad-spectrum antibiotics are used empirically in FCGS. Still, neither the occurrence of antimicrobial-resistant (AMR) bacteria nor potential patterns of co-occurrence between AMR genes and fungi have been documented in FCGS. This study explored the differential occurrence of AMR genes and the co-occurrence of AMR genes with oral fungal species. Briefly, 14 clinically healthy (CH) cats and 14 cats with FCGS were included. Using a sterile swab, oral tissue surfaces were sampled and submitted for 16S rRNA and ITS-2 next-generation DNA sequencing. Microbial DNA was analyzed using a proprietary curated database targeting AMR genes found in bacterial pathogens. The co-occurrence of AMR genes and fungi was tested using point biserial correlation. A total of 21 and 23 different AMR genes were detected in CH and FCGS cats, respectively. A comparison of AMR-gene frequencies between groups revealed statistically significant differences in the occurrence of genes conferring resistance to aminoglycosides (ant4Ib), beta-lactam (mecA), and macrolides (mphD and mphC). Two AMR genes (mecA and mphD) showed statistically significant co-occurrence with Malassezia restricta. In conclusion, resistance to clinically relevant antibiotics, such as beta-lactams and macrolides, is a significant cause for concern in the context of both feline and human medicine.

scholarly journals Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

2021 ◽  
Vol 9 (7) ◽  
pp. 1505
Author(s):  
Claire Roger ◽  
Benjamin Louart
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Clinical Manifestations ◽  
Acute Interstitial Nephritis ◽  
Convulsive Status Epilepticus ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Drug Induced ◽  
Icu Patients

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

Confronting the Challenge of Beta-Lactam Allergies: A Quasi-Experimental Study Assessing Impact of Pharmacy-Led Interventions

2017 ◽  
Vol 32 (2) ◽  
pp. 139-146 ◽  
Author(s):  
Steven C. Krey ◽  
Jeff Waise ◽  
Lee P. Skrupky
Keyword(s):  
Guideline Implementation ◽  
Tertiary Care ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Antibiotic Selection ◽  
Reaction Type ◽  
Care Community ◽  
Multidisciplinary Education ◽  
Quasi Experimental ◽  
Pharmacy Technicians

Objective: To improve allergy history documentation and increase the use of beta-lactams when appropriate in patients with a reported beta-lactam allergy. Methods: This pre–post study was conducted at a 167-bed tertiary care community hospital and evaluated multidisciplinary interventions on allergy documentation and antibiotic selection. Interventions included education, creation of local practice guidelines, and modified practices for pharmacists and pharmacy technicians. Inpatients with a reported beta-lactam allergy receiving at least 1 antibiotic for >24 hours were included; first admissions were assessed. Primary outcomes were documentation of reaction type and percentage of patients receiving non-beta-lactam therapy. Secondary outcomes included documentation of previously tolerated beta-lactams, modification of non-beta-lactam therapy, discharge antibiotics, and adverse reactions. Results: A total of 179 patients were included, 91 preintervention and 88 postintervention. No significant differences were observed between the before versus after groups in the percentage of patients with documentation of reaction type (90.1% vs 89.8%, P = .940) or the overall percentage of patients receiving non-beta-lactams (86.8% vs 84.1%, P = .605). However, significantly more patients in the after phase had documentation of previously tolerated beta-lactams (8.8% vs 28.4%, P = .001), and among patients receiving a non-beta-lactam, a greater percentage was subsequently switched to a beta-lactam (11.4% vs 25.7%, P = .022). One allergic reaction was documented during the study, which occurred in the before phase. Conclusion: Multidisciplinary education and local guideline implementation led by pharmacists may improve allergy documentation and antibiotic selection in patients with reported beta-lactam allergies.

scholarly journals Influence of Reported Penicillin Allergy on Mortality in MSSA Bacteremia

2018 ◽  
Vol 5 (3) ◽  
Author(s):  
Nicholas A Turner ◽  
Rebekah Moehring ◽  
Christina Sarubbi ◽  
Rebekah H Wrenn ◽  
Richard H Drew ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Multivariable Analysis ◽  
Mortality Rates ◽  
Penicillin Allergy ◽  
Care Hospital ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Appropriate Treatment ◽  
Large Tertiary Care ◽  
Multivariable Regression Models

Abstract Background Penicillin allergy frequently impacts antibiotic choice. As beta-lactams are superior to vancomycin in treating methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, we examined the effect of reported penicillin allergy on clinical outcomes in patients with MSSA bacteremia. Methods In this retrospective cohort study of adults with MSSA bacteremia admitted to a large tertiary care hospital, outcomes were examined according to reported penicillin allergy. Primary outcomes included 30-day and 90-day mortality rates. Multivariable regression models were developed to quantify the effect of reported penicillin allergy on mortality while adjusting for potential confounders. Results From 2010 to 2015, 318 patients with MSSA bacteremia were identified. Reported penicillin allergy had no significant effect on adjusted 30-day mortality (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.29–1.84; P = .51). Patients with reported penicillin allergy were more likely to receive vancomycin (38% vs 11%, P < .01), but a large number received cefazolin regardless of reported allergy (29 of 66, 44%). Mortality rates were highest among nonallergic patients receiving vancomycin (22.6% vs 7.4% for those receiving beta-lactams regardless of reported allergy, P < .01). In multivariable analysis, beta-lactam receipt was most strongly associated with survival (OR, 0.26; 95% CI, 0.12–0.54). Conclusions Reported penicillin allergy had no significant effect on 30- or 90-day mortality. Non-penicillin-allergic patients receiving vancomycin for treatment of MSSA bacteremia had the highest mortality rates overall. Receipt of a beta-lactam was the strongest predictor of survival. These results underscore the importance of correct classification of patients with penicillin allergy and appropriate treatment with a beta-lactam when tolerated.

scholarly journals Antipneumococcal activity of BAY 12-8039, a new quinolone, compared with activities of three other quinolones and four oral beta-lactams.

1997 ◽  
Vol 41 (12) ◽  
pp. 2786-2789 ◽  
Author(s):  
M A Visalli ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
Beta Lactam ◽  
Beta Lactams ◽  
Agar Dilution ◽  
Resistant Strains

Activities of BAY 12-8039 against 205 pneumococci were tested by agar dilution. MICs (in micrograms per milliliter) at which 50 and 90% of the isolates are inhibited (MIC50s and MIC90s, respectively) were 0.125 and 0.25 (BAY 12-8039), 2.0 and 4.0 (ciprofloxacin and ofloxacin), and 0.25 and 0.5 (sparfloxacin). Beta-lactam MIC50s and MIC90s for penicillin-susceptible, -intermediate, and -resistant strains, in that order, were 0.016 and 0.03, 0.25 and 2.0, and 2.0 and 4.0 (amoxicillin); 0.03 and 0.06, 0.25 and 4.0, and 4.0 and 8.0 (ampicillin); 0.03 and 0.06, 0.5 and 4.0, and 4.0 and 8.0 (cefuroxime); and 0.03 and 0.125, 0.25 and 2.0, and 4.0 and 8.0 (cefpodoxime). At two times their MICs after 24 h, BAY 12-8039, ciprofloxacin, ampicillin, and cefuroxime were uniformly bactericidal (99.9% killing) against 12 strains; other compounds were bactericidal at four times their MICs.

scholarly journals Could Dampening Expression of theNeisseria gonorrhoeaemtrCDE-Encoded Efflux Pump Be a Strategy To Preserve Currently or Resurrect Formerly Used Antibiotics To Treat Gonorrhea?

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Shaochun Chen ◽  
Kristie L. Connolly ◽  
Corinne Rouquette-Loughlin ◽  
Alexander D’Andrea ◽  
Ann E. Jerse ◽  
...  
Keyword(s):  
Genital Tract ◽  
Efflux Pump ◽  
Health Concern ◽  
Third Generation ◽  
Global Public Health ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Genital Tract Infection ◽  
Infected Female ◽  
Content Type

ABSTRACTNeisseria gonorrhoeaehas developed resistance to every antibiotic introduced for treatment of gonorrhea since 1938, and concern now exists that gonorrheal infections may become refractory to all available antibiotics approved for therapy. The current recommended dual antibiotic treatment regimen of ceftriaxone (CRO) and azithromycin (AZM) is threatened with the emergence of gonococcal strains displaying resistance to one or both of these antibiotics. Non-beta-lactamase resistance to penicillin and third-generation cephalosporins, as well as low-level AZM resistance expressed by gonococci, requires overexpression of themtrCDE-encoded efflux pump, which in wild-type (WT) strains is subject to transcriptional repression by MtrR. Since earlier studies showed that loss of MtrCDE renders gonococci hypersusceptible to beta-lactams and macrolides, we hypothesized that transcriptional dampening ofmtrCDEwould render an otherwise resistant strain susceptible to these antibiotics as assessed by antibiotic susceptibility testing and during experimental infection. In order to test this hypothesis, we ectopically expressed a WT copy of themtrRgene, which encodes the repressor of themtrCDEefflux pump operon, inN. gonorrhoeaestrain H041, the first reported gonococcal strain to cause a third-generation-cephalosporin-resistant infection. We now report that MtrR production can repress the expression ofmtrCDE, increase antimicrobial susceptibilityin vitro, and enhance beta-lactam efficacy in eliminating gonococci as assessed in a female mouse model of lower genital tract infection. We propose that strategies that target the MtrCDE efflux pump should be considered to counteract the increasing problem of antibiotic-resistant gonococci.IMPORTANCEThe emergence of gonococcal strains resistant to past or currently used antibiotics is a global public health concern, given the estimated 78 million infections that occur annually. The dearth of new antibiotics to treat gonorrhea demands that alternative curative strategies be considered to counteract antibiotic resistance expressed by gonococci. Herein, we show that decreased expression of a drug efflux pump that participates in gonococcal resistance to antibiotics can increase gonococcal susceptibility to beta-lactams and macrolides under laboratory conditions, as well as improve antibiotic-mediated clearance of gonococci from the genital tract of experimentally infected female mice.

scholarly journals Triple oral beta-lactam containing therapy for Buruli ulcer treatment shortening

2018 ◽  
Author(s):  
María Pilar Arenaz Callao ◽  
Rubén González del Río ◽  
Ainhoa Lucía Quintana ◽  
Charles J. Thompson ◽  
Alfonso Mendoza-Losana ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Amoxicillin Clavulanate ◽  
Low Toxicity ◽  
Potential Use ◽  
Ulcer Treatment

ABSTRACTThe potential use of clinically approved beta-lactams for Buruli ulcer (BU) treatment was investigated with representative classes analyzed in vitro for activity against Mycobacterium ulcerans. Beta-lactams tested were effective alone and displayed a strong synergistic profile in combination with antibiotics currently used to treat BU, i.e. rifampicin and clarithromycin; this activity was further potentiated in the presence of the beta-lactamase inhibitor clavulanate. In addition, quadruple combinations of rifampicin, clarithromycin, clavulanate and beta-lactams resulted in multiplicative reductions in their minimal inhibitory concentration (MIC) values. The MIC of amoxicillin against a panel of clinical isolates decreased more than 200-fold within this quadruple combination. Amoxicillin/clavulanate formulations are readily available with clinical pedigree, low toxicity, and orally and pediatric available; thus, supporting its potential inclusion as a new anti-BU drug in current combination therapies.

scholarly journals Inherent protection of bacteria from beta-lactam antibiotics by wet-dry cycles with microscopic surface wetness

2020 ◽  
Author(s):  
Yana Beizman-Magen ◽  
Maor Grinberg ◽  
Tomer Orevi ◽  
Nadav Kashtan
Keyword(s):  
Model Organism ◽  
Liquid Films ◽  
Interspecies Interactions ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Surface Wetness ◽  
Beta Lactam Antibiotics ◽  
Hygroscopic Salts ◽  
Antibiotic Response ◽  
Microscopic Surface

AbstractA large portion of bacterial life occurs on surfaces that are not constantly saturated with water and experience recurrent wet-dry cycles. While soil, plant leaves and roots, and many indoor surfaces may appear dry when not saturated with water, they are in fact often covered by thin liquid films and microdroplets, invisible to the naked eye, known as microscopic surface wetness (MSW). Such MSW, resulting from the condensation of water vapor to hygroscopic salts, is ubiquitous yet largely underexplored. A wide variety of antibiotics are abundant in environments where MSW occurs, yet little is known about bacterial response to antibiotics in wet-dry cycles and under MSW conditions. Using E. coli as a model organism, we show, through a combination of experiments and computational modeling, that bacteria are considerably more protected from beta-lactams under wet-dry cycles with MSW phases, than they are under constantly wet conditions. This is due to the combined effect of several mechanisms, including tolerance triggered by inherent properties of MSW, i.e., high salt concentrations and slow cell growth, and the deactivation of antibiotics due to physicochemical properties of MSW. Remarkably, we also find evidence for a cross-protection effect, where addition of lethal doses of antibiotic before drying significantly increases cells’ survival under MSW. As wet-dry cycles with MSW and beta-lactams, as well as other antibiotics, are common in vast terrestrial microbial habitats, our findings are expected to have significant implications for how we understand antibiotic response, population dynamics, and interspecies interactions in these globally important microbial ecosystems.

Characterizing the Microbiome of the Contracted Breast Capsule Using Next Generation Sequencing

2020 ◽  
Author(s):  
Jonathan Cook ◽  
Casey J Holmes ◽  
Roger Wixtrom ◽  
Martin I Newman ◽  
Jason N Pozner
Keyword(s):  
Next Generation Sequencing ◽  
Capsular Contracture ◽  
Bacterial Species ◽  
Fungal Species ◽  
Augmentation Mammoplasty ◽  
Next Generation ◽  
Level Of Evidence ◽  
Cutibacterium Acnes ◽  
Microbial Dna ◽  
Generation Sequencing

Abstract Background Recent work suggests that bacterial biofilms play a role in capsular contracture (CC). However, traditional culture techniques provide only a limited understanding of the bacterial communities present within the contracted breast. Next generation sequencing (NGS) represents an evolution of polymerase chain reaction technology that can sequence all DNA present in a given sample. Objectives The aim of this study was to utilize NGS to characterize the bacterial microbiome of the capsule in patients with CC following cosmetic breast augmentation. Methods We evaluated 32 consecutive patients with Baker grade III or IV CC following augmentation mammoplasty. Specimens were obtained from all contracted breasts (n = 53) during capsulectomy. Tissue specimens from contracted capsules as well as intraoperative swabs of the breast capsule and implant surfaces were obtained. Samples were sent to MicroGenDX Laboratories (Lubbock, TX) for NGS. Results Specimens collected from 18 of 32 patients (56%) revealed the presence of microbial DNA. The total number of positive samples was 22 of 53 (42%). Sequencing identified a total of 120 unique bacterial species and 6 unique fungal species. Specimens with microbial DNA yielded a mean [standard deviation] of 8.27 [4.8] microbial species per patient. The most frequently isolated species were Escherichia coli (25% of all isolates), Diaphorobacter nitroreducens (12%), Cutibacterium acnes (12%), Staphylococcus epidermidis (11%), fungal species (7%), and Staphylococcus aureus (6%). Conclusions NGS enables characterization of the bacterial ecosystem surrounding breast implants in unprecedented detail. This is a critical step towards understanding the role this microbiome plays in the development of CC. Level of Evidence: 4

scholarly journals In Vivo Activity of QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor, in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
David C. Griffith
Keyword(s):  
Klebsiella Pneumoniae ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Clinical Issue ◽  
Content Type ◽  
Beta Lactam Antibiotics ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

ABSTRACT Resistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant Klebsiella pneumoniae isolates in a neutropenic mouse thigh infection model. Neutropenic mice were infected with strains with potentiated beta-lactam MICs of ≤2 mg/liter in the presence of 8 mg/liter QPX7728. Two strains of carbapenem-resistant K. pneumoniae were tested with aztreonam, biapenem, cefepime, ceftazidime, ceftolozane, and meropenem alone or in combination with 12.5, 25, or 50 mg/kg of body weight of QPX7728 every 2 hours for 24 hours. Treatment with all beta-lactams alone either was bacteriostatic or allowed for bacterial growth. The combination of QPX7728 plus each of these beta-lactams produced bacterial killing at all QPX7728 doses tested. Overall, these data suggest that QPX7728 administered in combination with different partner beta-lactam antibiotics may have utility in the treatment of bacterial infections due to carbapenem-resistant K. pneumoniae.

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