Antinociceptive effects of cefadroxil and ceftriaxone in experimental animal models of pain.

BACKGROUND: As an "off-target" effect, cephalosporins can enhance glutamate transporter-1 expression in astrocytes to recycle glutamate from synaptic cleft, and exhibited analgesic properties in animals and humans with chronic pain. METHODS: In the present study, we focused on making a side-by-side comparison of the analgesic potentials of cefadroxil and ceftriaxone, using rodent models of peripheral neuropathic pain, inflammatory pain and incisional pain. Microdialysis technique was adopted to validate the in vivo glutamate regulatory properties of these two drugs in central nervous system. RESULTS: We have shown that cefadroxil and ceftriaxone are beneficial in a variety of pain scenarios, without inducing observable side effects. The two cephalosporins worked better on neuropathic pain, rather than inflammatory pain or incisional pain, suggesting nociceptive system was differentially affected. Further, microdialysis has confirmed that cephalosporins can effectively reverse the elevated levels of glutamate in brain of animals with neuropathic pain. CONCLUSIONS: The outcome of this study may guide us to identify a molecular skeleton derived from cefadroxil, based on which we could possibly develop new non-antibiotic analgesic compounds with glutamate recycling properties.

Degradation of cefadroxil drug by newly designed solar light responsive alcoholic template-based lanthanum ferrite nanoparticles.

In this work, lanthanum ferrite nanoparticles were synthesized via a simple co-precipitation method. Two different templates, namely sorbitol and mannitol, were used in this synthesis to tune the optical, structural, morphological, and photocatalytic properties of lanthanum ferrite. The synthesized lanthanum ferrite-sorbitol (LFOCo-So) and lanthanum ferrite-mannitol (LFOCo-Mo) were investigated through Ultraviolet-Visible (UV-Vis), X-ray diffraction (XRD), Fourier Transform Infra-Red (FTIR), Raman, Scanning Electron Microscopy-Energy Dispersive X-ray (SEM-EDX), and photoluminescence (PL) techniques to study the effects of the templates on the tunable properties of lanthanum ferrite nanoparticles. The UV-Vis study revealed a remarkably small bandgap (2.09 eV) of LFOCo-So compared to the LFOCo-Mo having a band gap of 2.46 eV. XRD analysis revealed a single-phased structure of LFOCo-So, whereas LFOCo-Mo showed different phases. The calculated crystallite sizes of LFOCo-So and LFOCo-Mo were 22 nm and 39 nm, respectively. FTIR spectroscopy indicated the characteristics of metal-oxygen vibrations of perovskites in both lanthanum ferrite (LFO) nanoparticles, whereas a slight shifting of Raman scattering modes in LFOCo-Mo in contrast to LFOCo-So showed the octahedral distortion of the perovskite by changing the template. SEM micrographs indicated porous particles of lanthanum ferrite with LFOCo-So being more uniformly distributed, and EDX confirmed the stoichiometric ratios of the lanthanum, iron, and oxygen in the fabricated lanthanum ferrite. The high-intensity green emission in the photoluminescence spectrum of LFOCo-So indicated more prominent oxygen vacancies than LFOCo-Mo. The photocatalytic efficiency of synthesized LFOCo-So and LFOCo-Mo was investigated against cefadroxil drug under solar light irradiation. At optimized photocatalytic conditions, LFOCo-So showed higher degradation efficiency of 87% in only 20 min than LFOCo-Mo having photocatalytic activity of 81%. The excellent recyclability of the LFOCo-So reflected that it could be reused without affecting photocatalytic efficiency. These findings showed that sorbitol is a useful template for the lanthanum ferrite particles imparting outstanding features, enabling it to be used as an efficient photocatalyst for environmental remediation.

Antibiotics in the Treatment of Uncomplicated Cystitis: A Google Trends Analysis.

INTRODUCTION: Using Google Trends (GT) data, the trend variations for the most common antibiotics used to treat uncomplicated cystitis were analyzed by time and region since 2004. METHODS: GT was used to create a "line-graph" that shows how interest in a topic in certain locations has grown or decreased over time. The relative search volume, which is displayed on a scale of 0-100, was used to index the search values for specific phrases. Nitrofurantoin (NFN), fosfomycin (FOS), trimethoprim (TMP), pivmecillinam (PIV), and cefadroxil are among the antibiotics recommended by the European Association of Urology (EAU) and the American Urological Association for the treatment of uncomplicated cystitis. Using the "global" inquiry category, the data was searched "worldwide" from 1 February 2004 to 31 December 2021. RESULTS: In the regression analysis, all antibiotics exhibited positive trends (p < 0.05). With a steady rise in popularity, NFN is the most popular antibiotic today. Search trend for cefadroxil stayed nearly stable until 2012, the rate of rise in the last 10 years increased, and cefadroxil is the second most popular antibiotic. In the previous 5 years, there was a decline in interest in TMP. In recent years, there was an increase in the trends for FOS and PIV. CONCLUSION: Clinicians and patients all around the world increasingly use the web to search for antibiotic therapies for uncomplicated cystitis. Antibiotics used to treat uncomplicated cystitis have various trends in different continents throughout the world. The web trends seem to be compatible with daily use.

Antimicrobial Resistance Profile of Bacteria Causing Pediatric Infections at the University Teaching Hospital in Rwanda.

Bacterial infections pose a global threat, especially in the pediatric population. Antimicrobials that are used to treat such infections continuously show reduced efficacy, and empirical therapy is a major treatment option in Rwanda. This study aimed to determine the resistance rate of commonly used antibiotics in pediatric patients. The study was conducted from June 1, 2018 to May 30, 2019, and microbiological samples were collected from 712 children with suspected bacterial infections. Antimicrobial sensitivity testing was performed on 177 positive cultures (24%) that were considered for data analysis. The findings show that the major bacterial isolates were Klebsiella pneumoniae (n = 50, 28.2%), Escherichia coli (n = 47, 26.5%), and Staphylococcus aureus (n = 38, 21.4%). In general, the greatest antibiotic resistance rate was observed in ampicillin (n = 125, 86.2%), amoxicillin-clavulanic acid (n = 84, 82.4%), amoxicillin (n = 64, 79%), cefadroxil (n = 83, 69.2%), tetracycline (n = 72, 59.7%), ceftazidime (n = 42, 55.3%), and cefuroxime (n = 14, 53.8%). More specifically, Klebsiella pneumoniae was 100% resistant to amoxicillin-clavulanic acid, cefuroxime, trimethoprim-sulfamethoxazole, ceftazidime, erythromycin, and clindamycin. Staphylococcus aureus was 86.7% resistant to ampicillin, and Escherichia coli was 91.7% resistant to tetracycline, 90.6% resistant to ampicillin, 83.3% resistant to amoxicillin-clavulanic acid, 79.3% resistant to cefadroxil, and 78.6% resistant to ceftazidime. Moreover, Klebsiella pneumoniae from blood and urine was 96.8% and 100% sensitive, respectively, to meropenem. Staphylococcus aureus from blood was 100% sensitive to vancomycin, whereas Escherichia coli from urine was sensitive to clindamycin (100%), nitrofurantoin (80.6%), and ciprofloxacin (72.7%). In conclusion, our findings show a high resistance rate to commonly used antibiotics, which suggests precaution in empirical therapy and continued surveillance of antimicrobial resistance.

Successful drainage of periaortic graft abscess and transcatheter aortic valve replacement in the same setting-A hybrid approach.

PRESENTATION: 81-year-old man with a history of Bio-Bentall surgery presented to the emergency department with fever, chills and back pain. Initial physical examination was inconclusive apart from sudden onset of delirium. INVESTIGATION: Elevated white blood cells, anemia, and neutrophilia. Further studies revealed gram-positive cocci on the initial blood culture, which was then confirmed to be Methicillin Sensitive Staph Aureus bacteremia. Subsequently, a transesophageal echocardiography showed a periaortic abscess, moderate aortic regurgitation and severe aortic stenosis with no evidence of endocarditis. MANAGEMENT: Antibiotics were started and urgent abscess drainage was planned. In a hybrid operative setting, a multidisciplinary team of cardiology, and cardiac surgery managed the periaortic graft abscess drainage through a median sternotomy and transcatheter aortic valve replacement. Postoperatively, the complications included bradycardia, and right heart failure. Six-week course of IV Rifampin, Probenecid, and Cefazolin was initiated, and patient was to remain on lifelong Cefadroxil. CONCLUSION: A hybrid approach should be considered for patients with high morality risks in the field of cardiovascular medicine as it offers the best available combination of treatments.

Cefadroxil Use for Musculoskeletal Infections in an Academic Pediatric Hospital.

Forty-nine of 52 (94.2%) children with musculoskeletal infection (MSKI) were successfully treated with cefadroxil dosed at 30 mg/kg/day over a 10-year time period. Two failures were associated with poor medication adherence. Our study suggests that treatment of MSKI with cefadroxil offers acceptable outcomes. Confirmation through clinical trials is appropriate.

Cefadroxil Comparable to Cephalexin: Minimum Inhibitory Concentrations among Methicillin-Susceptible Staphylococcus aureus Isolates from Pediatric Musculoskeletal Infections.

Cephalexin and cefadroxil are oral first-generation cephalosporins used to treat methicillin-susceptible Staphylococcus aureus (MSSA) infections. Despite its shorter half-life, cephalexin is more frequently prescribed, although cefadroxil is an appealing alternative, given its slower clearance and possibility for less frequent dosing. We report comparative MIC distributions for cefadroxil and cephalexin, as well as for oxacillin, cephalothin, ceftaroline, and cefazolin, for 48 unique clinical MSSA isolates from pediatric patients with musculoskeletal infections. Both cefadroxil and cephalexin had MIC50 values of 2 µg/mL and MIC90 values of 4 µg/mL. MIC50s for oxacillin, cephalothin, and ceftaroline were ≤0.25 µg/mL, and cefazolin's MIC50 was 0.5 µg/mL. While cefadroxil and cephalexin MICs are higher than those for other active agents, the distributions of MICs for cefadroxil and cephalexin are statistically equivalent, suggesting similar in vitro MSSA activities. Cefadroxil should be further considered an alternative agent to cephalexin, although additional work is needed to identify the optimal dose and frequency of these antibiotics for the treatment of serious MSSA infections. IMPORTANCE Cephalexin and cefadroxil are oral antibiotics that are used to treat serious infections due to the bacteria MSSA. While cephalexin is used more commonly, cefadroxil is excreted from the body more slowly; this generally allows patients to take cefadroxil less frequently than cephalexin. In this study, we compared the abilities of cefadroxil, cephalexin, and several other representative intravenous antibiotics to inhibit the growth of MSSA in the laboratory. Bacterial samples were obtained from children with bone, joint, and/or muscle infections caused by MSSA. We found that cefadroxil and cephalexin inhibited the growth of MSSA at similar concentrations, suggesting similar antibacterial potencies. The selected intravenous antistaphylococcal antibiotics generally inhibited bacterial growth with lower antibiotic concentrations. Based on these results, cefadroxil should be further considered an alternative oral antibiotic to cephalexin, although future research is needed to identify the optimal dose and frequency of these antibiotics for serious infections.

The Cost-Effectiveness of Extended Oral Antibiotic Prophylaxis for Infection Prevention After Total Joint Arthroplasty in High-Risk Patients.

BACKGROUND: Extended oral antibiotic prophylaxis may decrease rates of prosthetic joint infection (PJI) after total joint arthroplasty (TJA) in patients at high risk for infection. However, the cost-effectiveness of this practice is not clear. In this study, we used a break-even economic model to determine the cost-effectiveness of routine extended oral antibiotic prophylaxis for PJI prevention in high-risk TJA patients. METHODS: Baseline PJI rates in high-risk patients, the cost of revision arthroplasty for PJI, and the costs of extended oral antibiotic prophylaxis regimens were obtained from the literature and institutional purchasing records. These variables were incorporated in a break-even economic model to calculate the absolute risk reduction (ARR) in infection rate necessary for extended oral antibiotic prophylaxis to be cost-effective. ARR was used to determine the number needed to treat (NNT). RESULTS: Extended oral antibiotic prophylaxis with Cefadroxil in patients at high risk for PJI was cost-effective at an ARR in baseline infection rate of 0.187% (NNT = 535) and 0.151% (NNT = 662) for TKA and THA, respectively. Cost-effectiveness was preserved with varying costs of antibiotic regimens, PJI treatment costs, and infection rates. CONCLUSION: The use of extended oral antibiotic prophylaxis may reduce PJI rates in patients at high risk for infection following TJA and appears to be cost-effective. However, the current evidence supporting this practice is limited in quality. The use of extended oral antibiotic prophylaxis should be weighed against the possible development of future antimicrobial resistance, which may change the value proposition.

A mechanism for matrikine regulation in acute inflammatory lung injury.

Proline-glycine-proline (PGP) and its acetylated form (Ac-PGP) are neutrophil chemoattractants generated by collagen degradation, and they have been shown to play a role in chronic inflammatory disease. However, the mechanism for matrikine regulation in acute inflammation has not been well established. Here, we show that these peptides are actively transported from the lung by the oligopeptide transporter, PEPT2. Following intratracheal instillation of Ac-PGP in a mouse model, there was a rapid decline in concentration of the labeled peptide in the bronchoalveolar lavage (BAL) over time and redistribution to extrapulmonary sites. In vitro knockdown of the PEPT2 transporter in airway epithelia or use of a competitive inhibitor of PEPT2, cefadroxil, significantly reduced uptake of Ac-PGP. Animals that received intratracheal Ac-PGP plus cefadroxil had higher levels of Ac-PGP in BAL and lung tissue. Utilizing an acute LPS-induced lung injury model, we demonstrate that PEPT2 blockade enhanced pulmonary Ac-PGP levels and lung inflammation. We further validated this effect using clinical samples from patients with acute lung injury in coculture with airway epithelia. This is the first study to our knowledge to determine the in vitro and in vivo significance of active matrikine transport as a mechanism of modulating acute inflammation and to demonstrate that it may serve as a potential therapeutic target.

Absorbable antibiotic beads as an adjuvant therapy in treating ventricular assist devices driveline infection: A case report.

BACKGROUND: Ventricular assist devices driveline infections are common, recalcitrant, and carry high morbidity and mortality. Herein, we reported a patient with driveline infection that was successfully treated with a combination of systemic antibiotics, surgical debridement, and instillation of absorbable antibiotic beads to the wound bed. METHODS AND RESULTS: A 39-year-old man with nonischemic cardiomyopathy underwent insertion of a continuous flow left ventricular assist device. Four years postoperatively, the patient presented with clinical, laboratory, and radiologic signs of driveline tract infection. He underwent extensive surgical debridement, installation of absorbable antibiotic beads that consisted of calcium sulfate, vancomycin, and tobramycin, into the wound bed, and systemic antibiotics. The patient was free of infection 9 month postoperatively. CONCLUSION: Absorbable calcium sulfate antibiotic beads may serve as a beneficial adjunct to surgical debridement and systemic antibiotics for the treatment of ventricular assist device driveline infection, and merit further investigation.

A Critical Review of Cephalexin and Cefadroxil for the Treatment of Acute Uncomplicated Lower Urinary Tract Infection in the Era of "Bad Bugs, Few Drugs".

First-generation oral cephalosporins (cephalexin and cefadroxil) have traditionally been considered second-line treatment options for uncomplicated lower urinary tract infections (uLUTIs).  However, in the current age of "bad bugs, few drugs", where there are increasingly limited oral options against resistant Enterobacteriaceae, there is an urgent need to rethink how best to utilize the available antibiotic armamentarium.  This review examines the historical clinical trials and experimental studies of cephalexin and cefadroxil, particularly through the modern lens of pharmacokinetics/pharmacodynamics (PK/PD), to better appreciate the efficacy of these drugs in uLUTIs.  Furthermore, newer cefazolin-cephalexin surrogate testing, as recommended by the Clinical and Laboratory Standards Institute (CLSI) and the United States Committee on Antimicrobial Susceptibility Testing (USCAST), has recategorized cephalexin in many instances from resistant to susceptible.  We conclude that cephalexin and cefadroxil have very good early bacteriological and clinical cures in uLUTIs due to non-extended-spectrum beta-lactamase-producing (ESBL) Enterobacteriaceae comparable to many traditionally first-line agents.  Cephalexin can be conveniently administered as 500 mg twice or thrice daily, similar to cefadroxil (500 mg twice daily); therefore, either agent may be used as a fluoroquinolone-sparing alternative. Cephalexin may be the more practical choice for many clinicians because reliable antimicrobial susceptibility test interpretative criteria (STIC) are provided by CLSI, USCAST, and the European Committee on Antimicrobial Susceptibility Testing (EUCAST), whereas direct cefadroxil STIC is offered only by EUCAST.

Reanalysis of cefazolin surrogate susceptibility breakpoints utilized as guidances for oral cephalosporin treatments of uncomplicated urinary tract infections: caution concerning application to cefadroxil.

Based on antimicrobial susceptibility test interpretive breakpoint criteria from Clinical and Laboratory Standards Institute and United States Committee on Antimicrobial Susceptibility Testing, cefazolin uncomplicated urinary tract infection (uUTI) surrogate breakpoints do not accurately predict cefadroxil or cephradine susceptibility when testing indicated Enterobacteriaceae species isolates. Hence, these two orally-administered cephalosporins (OC) are not equivalent spectrum substitutes for cephalexin or six other related OC agents for contemporary uUTI therapy.

Fabrication, physical characterizations and in vitro antibacterial activity of cefadroxil-loaded chitosan/poly(vinyl alcohol) nanofibers against Staphylococcus aureus clinical isolates.

Particular attention is devoting to the design of electrospun nanofibers (NFs) as new drug delivery nanosystems to overcome bacterial resistance and toxicological issues. Their advantages include high encapsulation efficiency, great drug-loading capacity, easiness in production, cost-effectiveness, and controlled targeted drug delivery. We aim to characterize electrospun chitosan (CS)/poly(vinyl alcohol) (PVA) NFs (CPNFs) loaded with cefadroxil monohydrate (CFX), a broad spectrum antibiotic. The biodegradable and biocompatible carrier system was greenly fabricated by electrospinning at various CS/PVA ratios. CPNFs were characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and UV-spectrometry. Their potential toxicity was evaluated in human epidermal keratinocytes by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Their antibacterial activity was tested by agar well diffusion method and MTT assay against clinical isolates of Staphylococcus aureus, a Gram-positive bacterium involved in serious skin infections. The thermostable CFX-loaded CPNFs at optimized 30:70 ratio revealed a burst and sustained release profile that occurred predominantly by diffusion following non-Fickian (anomalous) transport mechanism, as well as a more potent and safe antibacterial than free CFX. Thus, electrospun CFX-loaded CPNFs could be a new promising transdermal drug delivery system to activate the wound healing process and cost-effectively treat S. aureus-induced (resistant) skin infections.

Derivative constant wavelength synchronous fluorescence spectrometry for the simultaneous detection of cefadrine and cefadroxil in water samples.

A sensitive accurate spectrofluorimetric technique was developed to detect cefadroxil and cefradine traces in water samples simultaneously, by applying a procedure based on the formation of hydrolysis products corresponding to these compounds by sodium hydroxide (1 N NaOH) treatment. The conventional and the synchronous fluorescence spectra of these hydrolyzed products were totally overlapped making resolving of this mixture impossible. The second-derivative constant-wavelength synchronous fluorescence spectra allowed their detection simultaneously in a single scan after experimental conditions optimization, which was measured at 390 nm and 379 nm for cefadroxil and cefradine, respectively at Δλ = 30.0. The calibration curves between derivative synchronous fluorescence intensity and drugs concentration showed suitable linear correlation in the range of 0.1 to 5 µg.mL-1 for cefadroxil and 0.5-10 µg.mL-1 for cefradine. The proposed fluorimetric method is superior in being simple, environmental friendly and cost effective in comparison to the previously published reported methods.

Transient Fanconi Syndrome After Treatment with Firocoxib, Cefadroxil, Tramadol, and Famotidine in a Maltese.

Fanconi syndrome is a renal proximal tubulopathy characterized by excessive urinary loss of glucose, amino acids, several electrolytes, and bicarbonate. Here, we report the case of transient Fanconi syndrome in a dog following administration of firocoxib, cefadroxil, tramadol, and famotidine. A 10 mo old Maltese was presented with lethargy, anorexia, vomiting, and weight loss. Transient Fanconi syndrome without azotemia was associated with firocoxib, cefadroxil, tramadol, and famotidine treatment. The dog received supportive care including IV fluids, gastroprotectants, and oral nutritional supplements. Two months after initial diagnosis and treatment, the dog showed complete resolution of glucosuria and aminoaciduria. The unique features of Fanconi syndrome in this case emphasize the potential renal tubular toxicity of this widely used multiple-drug combination.

Optimized Photoelectrochemical Detection of Essential Drugs Bearing Phenolic Groups.

The World Health Organization (WHO) model "List of Essential Medicines" includes among indispensable medicines antibacterials and pain and migraine relievers. Monitoring their concentration in the environment, while challenging, is important in the context of antibiotic resistance as well as their production of highly toxic compounds via hydrolysis. Traditional detection methods such as high-performance liquid chromatography (HPLC) or LC combined with tandem mass spectrometry or UV-vis spectroscopy are time-consuming, have a high cost, require skilled operators and are difficult to adapt for field operations. In contrast, (electrochemical) sensors have elicited interest because of their rapid response, high selectivity, and sensitivity as well as potential for on-site detection. Previously, we reported a novel sensor system based on a type II photosensitizer, which combines the advantages of enzymatic sensors (high sensitivity) and photoelectrochemical sensors (easy baseline subtraction). Under red-light illumination, the photosensitizer produces singlet oxygen which oxidizes phenolic compounds present in the sample. The subsequent reduction of the oxidized phenolic compounds at the electrode surface gives rise to a quantifiable photocurrent and leads to the generation of a redox cycle. Herein we report the optimization in terms of pH and applied potential of the photoelectrochemical detection of the hydrolysis product of paracetamol, i.e., 4-aminophenol (4-AP), and two antibacterials, namely, cefadroxil (CFD, ß-lactam antibiotic) and doxycycline (DXC, tetracycline antibiotic). The optimized conditions resulted in a detection limit of 0.2 µmol L-1 for DXC, but in a 10 times higher sensitivity, 20 nmol L-1, for CFD. An even higher sensitivity, 7 nmol L-1, was noted for 4-AP.

In Silico Prediction of the Absorption and Disposition of Cefadroxil in Humans using an Intestinal Permeability Method Scaled from Humanized PepT1 Mice.

It is difficult to predict the pharmacokinetics and plasma concentration-time profiles of new chemical entities in humans based on animal data. Some pharmacokinetic parameters, such as clearance and volume of distribution, can be scaled allometrically from rodents, mammals, and nonhuman primates with good success. However, it is far more challenging to predict the oral pharmacokinetics of experimental drug candidates. In the present study, we used in situ estimates of intestinal permeability, obtained in silico and from rat, wild-type (WT), and humanized PepT1 (huPepT1) mice, to predict the systemic exposure of cefadroxil, an orally administered model compound, under a variety of conditions. Using the GastroPlus simulation software program (Simulations Plus, Lancaster, CA), we found that the C max and area under the plasma concentration-time curve from time zero to the last measurable concentration of cefadroxil were better predicted using intestinal permeability estimates (both segmental and jejunal) from huPepT1 than from WT mice, and that intestinal permeabilities based on in silico and rat estimates gave worse predictions. We also observed that accurate predictions were possible for cefadroxil during oral dose escalation (i.e., 5, 15, and 30 mg/kg cefadroxil), a drug-drug interaction study (i.e., 5 mg/kg oral cefadroxil plus 45 mg/kg oral cephalexin), and an oral multiple dose study [i.e., 500 mg (6.7 mg/kg) cefadroxil every 6 hours]. Finally, the greatest amount of cefadroxil was absorbed in duodenal and jejunal segments of the small intestine after a 5 mg/kg oral dose. Thus, by combining a humanized mouse model and in silico software, the present study offers a novel strategy for better translating preclinical pharmacokinetic data to oral drug exposure during first-in-human studies.