Cefadroxil and cephalexin pharmacokinetics and pharmacodynamics in children with musculoskeletal infections.

Cephalexin, a first-generation cephalosporin, is the first-line oral therapy for children with musculoskeletal infections due to methicillin-susceptible Staphylococcus aureus (MSSA). Cefadroxil, a similar first-generation cephalosporin, is an attractive alternative to cephalexin given its longer half-life. In this study, we describe the comparative pharmacokinetics (PK) and pharmacodynamics (PD) of cephalexin and cefadroxil in children with musculoskeletal infections. Children aged 6 months to 18 years with a musculoskeletal infection were enrolled in a prospective, open-label, crossover PK study and given single oral doses of cefadroxil (50-75 mg/kg up to 2,000 mg) and cephalexin (50 mg/kg up to 1,375 mg). Population PK models were developed and used for dosing simulations. Our primary PD target was the achievement of free antibiotic concentrations above the minimum inhibitory concentration (fT >MIC) for 40% of the day for MICs ≤ 4 mg/L. PK of cephalexin (n = 15) and cefadroxil (n = 14) were best described using a one-compartment, first-order absorption model, with a lag time component for cefadroxil. PK parameters were notable for cefadroxil's longer half-life (1.61 h) than cephalexin's (1.10 h). For pediatric weight bands, our primary PD target was achieved by cephalexin 25 mg/kg/dose, maximum 750 mg/dose, administered three times daily and cefadroxil 40 mg/kg/dose, maximum 1,500 mg/dose, administered twice daily. More aggressive dosing was required to achieve higher PD targets. Among children with musculoskeletal infections, oral cephalexin and cefadroxil achieved PD targets for efficacy against MSSA. Given less frequent dosing, twice-daily cefadroxil should be further considered as an alternative to cephalexin for oral step-down therapy for serious infections due to MSSA.

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.

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.

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.

[Nephronia in pediatrics: part of the spectrum of upper urinary tract infections. Clinical cases and review of the literature]. / Nefronia en pediatría: dentro del espectro de las infecciones urinarias. Serie clínica y revisión de la literatura.

Nephronia or focal acute nephritis corresponds to a localized inflammatory non-liquefactive kidney infection which may involve parenchyma of one or more renal lobes. It has been suggested that nephronia is part of the spectrum of upper urinary tract infections between acute pyelonephritis and renal abscess. It is associated with a prolonged clinical course, higher levels of inflammatory markers and an increased risk of renal scarring, compared to pyelonephritis. Ultrasound plays a useful role. Nephronia is an under-diagnosed condition, thus, clinical suspicion is important for early diagnosis and appropriate treatment. We present three paediatric cases, and a review of the literature.

A retrospective analysis of skin bacterial colonisation, susceptibility and resistance in atopic dermatitis and impetigo patients.

Atopic dermatitis (AD) and impetigo are skin conditions where bacterial colonisation and infection, especially with Staphylococcus aureus play an important role. We compared skin bacterial population, resistance patterns and choice of antimicrobial agents in patients diagnosed with AD and impetigo during 2005 and 2011 in our department. Number of positive cultures in the AD group were 40 and 53 in 2005 and 2011, with S. aureus found in 97.5% and 100%, respectively. Differences in resistance were marginal. In impetigo, S. aureus was found in all 70 patients in 2005 and all 40 patients in 2011. Antibiotic resistance to specifically fusidic acid was more common in 2005 impetigo patients (22.8%) versus 2011 (5%) (p = 0.078). The most commonly used oral antimicrobial was cefadroxil (in 57.5% and 52.8% of AD and 58.6% and 35% of impetigo patients in 2005 and 2011, respectively). Our observations confirm the high prevalence of S. aureus in both diseases and, interestingly, show a declining resistance trend in impetigo.

Reconstrução mamária imediata com retalho do músculo grande dorsal e implante de silicone / Immediate breast reconstruction with latissimus dorsi flap and silicone implant

Introdução: O primeiro tratamento eficaz para o câncer de mama foi descrito em 1894. A partir das décadas de 60 e 70, cirurgias menos agressivas foram desenvolvidas, sem prejuízos oncológicos. Com evolução histórica semelhante, o retalho do músculo grande dorsal (RMGD) foi introduzido em 1906. Contudo, apenas 70 anos após sua primeira descrição, ele ganhou popularidade como uma opção para as reconstruções mamárias. Método: Estudo clínico retrospectivo realizado por meio da coleta de dados de 22 pacientes submetidas à reconstrução mamária imediata com emprego do RMGD associado a implante de silicone durante o período de fevereiro de 2012 a dezembro de 2013. Resultados: Não houve necrose do retalho de grande dorsal ou perda da reconstrução mamária nos casos estudados. Foram observados 10 casos (45%) de seroma em região dorsal, 3 casos (14%) de necrose parcial da pele da mastectomia e 3 casos (14%) de deiscência parcial da ferida operatória. Não foram evidenciados fatores de risco com significância estatística para as complicações apresentadas. Ocorreram 4 casos (18,18%) de alterações de cobertura do implante, com atrofia muscular e cutânea, e 2 casos (9,09%) de contratura capsular. Apenas um caso não foi associado à radioterapia. Contudo, não houve significância estatística em relação à radioterapia adjuvante e às complicações tardias apresentadas (p = 0,635). Conclusão: O RMGD associado ao implante de silicone é uma opção segura e confiável para a reconstrução mamária imediata após mastectomias.

Introduction: The first effective breast cancer treatment was described in 1894. Less aggressive surgeries were developed in the 1960s and 70s, without increased mortality due to cancer. With similar historical evolution, the latissimus dorsi muscle flap (LDMF) procedure was introduced in 1906. Seventy years after its first description, LDMF gained popularity as an option for breast reconstruction. Method: A retrospective clinical study was conducted using data obtained from 22 patients undergoing immediate breast reconstruction with LDMF and silicone implants between February 2012 and December 2013. Results: No latissimus dorsi flap necrosis or breast reconstruction losses were observed in this study. Ten cases (45%) of seroma were detected in the dorsal region, three cases (14%) of partial necrosis of the mastectomized skin, and three cases (14%) of partial surgical wound dehiscence. Statistical significant risk factors for the complications observed have not been emphasized. There were four cases (18.18%) of muscle and skin atrophy associated with implants, and two cases (9.09%) of capsular contracture. Only one case was not associated with radiotherapy. However, there were no statistically significant differences in adjuvant radiotherapy and late complications (p = 0.635). Conclusion: LDMF associated with silicone implants is a safe and reliable option for immediate breast reconstruction after mastectomies.

Case report: Long-standing complex regional pain syndrome relieved by a cephalosporin antibiotic.

We describe a young woman who had had treatment-refractory complex regional pain syndrome (CRPS) for 6 years before receiving antibiotic treatment with cefadroxil (a cephalosporin derivative) for a minor infection. Cefadroxil reduced the patient's pain and motor dysfunction (dystonia and impaired voluntary movement) within days; the pain and motor disorder returned when cefadroxil was discontinued; and both again abated when cefadroxil was re-instituted. The patient has now had symptom relief for more than 3 years on continuing cefadroxil therapy. We discuss this case in the context of previous reports of antibiotic treatment relieving neuropathic pain in experimental animals.

Profilaxis antimicrobiana en cirugía ortopédica: cefazolina vs cefadroxilo IV / Antimicrobial prophylaxis in orthopedic surgery: cefazolina vs cefadroxilo IV

Toda intervención quirúrgica está expuesta a infectarse. La necesidad de profilaxis antimicrobiana en cirugía ortopédica para casos quirúrgicos agudos o electivas de cirugías limpias ha sido establecida como procedimiento de rutina. En Cirugía Ortopédica y Traumatología cuando se requiere el uso de implantes metálicos con el fin de realizar osteosíntesis o sustitución de las superficies articulares, aumenta el riesgo de infección, por tratarse de materiales extraños que son introducidos en el organismo. En estos casos la antibióticoterapia preventiva es de primordial importancia. Se realizó un estudio de profilaxis antimicrobiana, multicéntrico, aleatorizado, prospectivo, doble ciego, comparativo de grupos paralelos, con el fin de evaluar la eficacia de Cefadroxilo I.V. Vs. Cefazolina I.V. como antibióticos profilácticos mediante la determinación del número de pacientes infectados en cirugía de fracturas cerradas en la cuales se colocó material de síntesis. Se completaron 58 pacientes, 34 en el grupo de cefadroxilo y 24 en el grupo de cefazolina, al inicio los grupos fueron similares en cuanto a edad, sexo, tipo de fractura, tiempo de intervención, tiempo entre la fractura y la intervención.Más pacientes en el grupo de cefadroxilo tenían el tiempo máximo autorizado entre la fractura y la intervención (p: 0,07). Se presentó en el grupo de cefadroxilo una infección de la herida operatoria y un caso de eritema leve que cedió con tratamiento oral con cefadroxilo, sin diferencias entre los grupos.Hubo tres casos de eventos adversos, reacción anafiláctica a las 48 horas en el grupo de cefazolina que ameritó finalización de protocolo y hematoma en miembro inferior derecho y, en el grupo de cefadroxilo, una elevación discreta de enzimas hepáticas. La respuesta terapéutica de profilaxis antimicrobianano mostró diferencia entre los grupos. El cefadroxilo es tan eficaz como la cefazolina para la profilaxis antimicrobiana en pacientes con fracturas...

Any operation is exposed to infection. The need for antimicrobial prophylaxis in orthopedic surgery for acute or elective surgical cases of clean surgery is established as a routine procedure. Orthopedic Surgery when required the use of metallic implants in order to perform internal fixation or replacement of the articular surfaces, increases the risk of infection because they are foreign materials are introduced into the body. In these cases, preventive antibiotic therapy is very important. We performed a study of antimicrobialprophylaxis multicenter, randomized, prospective, double-blind, parallel group comparison in order to evaluate the effectiveness of Cefadroxil IV vs. Cefazolin I.V. as prophylactic antibiotics by determining the number of infected patients after fracture surgery in which synthetic material was placed. Fifty eigth patients were completed, 34 in the cefadroxil group and 24 in the cefazolin group, at the beginning the groups were similar in age, sex, fracture type, operative time, time between fracture and surgery. More patients in the cefadroxil group had the maximum allo-wable time between the fracture and surgery. (P: 0.07). In the cefadroxil group we found a wound infection and one case of mild erythema which resolved with oral treatment with cefadroxil, without differences between groups. There were three cases of adverse events, anaphylactic reaction to cefazolin at 48 h in the group that required finalization of protocol and hematoma in right leg and in the cefadroxil group, a moderate increase in liver enzymes. The therapeutic response of antimicrobial prophylaxis showed no difference between groups. Cefadroxil is as effective as cefazolin for antimicrobial prophylaxis in patients with fractures that warrant placement of synthetic material

Nefritis aguda focal: caso clínico / Focal acute nephritis: a case report

Focal acute nephritis (FAN) or acute lobar nephronia is a rare clinical picture characterized by an infection localized in the kidney, with an inflammatory mass without liquefaction. Of variable clinical manifestations, diagnosis is achieved through CT scanning. Histologically, unlike acute pyelonephritis, it does not present a diffuse infíltrate. Objective: Case report of FAN in a pediatric patient. Case Report: Ten year old male complaining of abdominal pain, presents painful percussion in the right lumbar fossa. Urinary analysis and culture were negative, renal sonogram was negative. Abdominal CT sean showed múltiple hypodense renal foci. He responded well to cephotaxim, being discharged in the third day of hospitalization with completion of treatment as outpatient. Differential diagnosis with Acute Pyelonephritis is very important, as it requires controlled and opportune treatment to prevent renal absceses. Diagnosis of this pathology must be pursued despite a normal UA.

La nefritis aguda focal o nefronia lobar aguda constituye un cuadro poco común caracterizado por una infección localizada en el riñon, la que corresponde a una masa inflamatoria sin licuefacción. Posee una clínica variable, siendo la tomograña computada (TAC) la prueba más sensible y específica para el diagnóstico de esta enfermedad. Esta patología se diferencia histológicamente de la pielonefritis aguda por no presentar un infiltrado inflamatorio difuso. Objetivo: presentar un caso de nefronia aguda multifocal en un paciente pediátrico. Caso clínico: Escolar de 10 años que consultó por dolor abdominal, al examen destacaba la presencia de percusión dolorosa en fosa lumbar. Los exámenes de orina y urocultivo fueron negativos. Al ingreso no se detectó cambios renales ecográficamente evidenciables. Se realizó un TAC de abdomen que mostraba múltiples focos renales hipodensos. Respondió favorablemente a terapia antibiótica con cefotaxima siendo dado de alta al tercer día, completando terapia en forma ambulatoria. La diferenciación de este cuadro de otros procesos renales como la pielonefritis aguda (PNA) es muy importante, ya que precisa un tratamiento oportuno y controlado por el riesgo de evolucionar a absceso renal. El diagnóstico de esta patología debe ser buscado a pesar de contar con exámenes de orina negativos.

Shewanelia putrefaciens: a rare microbial agent associated with a non-healing ulcer in a leprosy patient.

Female aged 55 years presented with signs and symptoms of borderline lepromatous leprosy and presence of a non-healing ulcer and multiple haemorrhagic blisters over dorsum of both feet. Discharge from the various lesions was subjected to microbiological examination and an unusual organism Shewanella purtefaciens was isolated which was sensitive to most routine antibiotics. Patient responded well to cephadroxil therapy with uneventful and complete healing of ulcer and blisters.

Utilidad del cefadroxilo en leishmaniosis tegumentaria americana con infecciones piógenas sobreagregadas / Use of cefadroxil for american tegumentary leishmaniosis with intercurrent pyogenic infections

La leishmaniosis tegumentaria americana es un problema de salud en el medio rural venezolano. Las úlceras leishmánicas tienden a infectarse secundariamente por bacterias piógenas. Se evaluaron 41 pacientes con la enfermedad que recibieron cefadroxilo oral previo a la toma de segmentos de piel del borde de las úlceras para la demostración microscópica de Leishmania spp. La mayoría de los pacientes eran adultos masculinos y provenían del medio rural del estado Miranda, con una úlcera única localizada en los miembros inferiores. El diagnóstico inmunoserológico se efectuó por leishmanina y anticuerpos fluorescentes y el de certeza por visualización de amastigotes en frotis coloreados. Los resultados inmunoserológicos fueron positivos en todos los pacientes, mientras que el parásito se observó en 51 por ciento de los frotis coloreados con Giemsa. Una semana postratamiento antimicrobiano, los pacientes presentaban mejoría de las infecciones sobreagregadas y también progreso en la visualización del parásito por disminución de la carga bacteriana. Los pacientes fueron tratados con antimoniato de meglumina intramuscular en series de 10 días, con reposo intermedio. Respondieron adecuadamente, las lesiones cicatrizaron y los nódulos satelitales acompañantes desaparecieron. Se concluye que el cefadroxilo es útil para tratar las infecciones piógenas secundarias asociadas en LTA y aumentar la sensibilidad para observar los parásitos en piel. La leishmaniosis considerada como enfermedad emergente, motiva la búsqueda de alternativas terapéuticas adecuadas

Cutaneous leishmaniosis of the New World (CLNW) is a health problem in rural areas of Venezuela. Patients with muco-cutaneous ulcers tend to present intercurrent infections of the lesions by pyogenic bacteria. After removing skin specimens from the ulcer borders for microscopic demonstration of Leishmania spp amastigotes, forty-one patients with the disease, being treated with cefadroxil per os were studied. Most of the patients came from rural Miranda state, were male adults and had one ulcer on a lower limb. Confirmatory diagnosis was made using the Montenegro test, or Leishmanin immunoserology (IFAT) and demonstration of the presence of parasites in the skin samples. All the patients were positive for the Leishmanin test, while parasites were observed in 51 percent of the skin smears colored by the Giemsa procedure. After a week of treatment with cefadroxil, bacterial infections were reduced and a decrease in bacterial load was also noted when visualizing the parasite from the skin smears. Patients were treated with intramuscular antimony meglumine for 10-day periods with an intervening rest period. All patients responded adequately to the meglumine antileishmania treatment; the lesions healed and accompanying tributary lymph nodes disappeared. Conclusion: Cefadroxil is a suitable antibiotic for treating intercurrent pyogenic infections in cases of tegumentary leishmaniosis. Since leishmaniosis is considered an emerging disease, a search for appropriate, alternative therapies is required

Efficacy and safety of cefovecin in treating bacterial folliculitis, abscesses, or infected wounds in dogs.

OBJECTIVE: To evaluate the efficacy and safety of administration of cefovecin, compared with cefadroxil, for treatment of naturally occurring secondary superficial pyoderma, abscesses, and infected wounds in dogs. DESIGN: Multicenter, randomized, positive-controlled clinical trial. ANIMALS: 235 client-owned dogs. PROCEDURES: Dogs with clinical signs of skin infection confirmed via bacteriologic culture were randomly allocated to receive a single SC injection of cefovecin (8 mg/kg [3.6 mg/lb]) followed by placebo administered PO twice daily for 14 days or cefadroxil (22 mg/kg [10 mg/lb]) administered PO twice daily for 14 days following a placebo injection. Two 14-day treatment courses were permitted. Treatment success was defined as reduction of clinical signs to mild or absent at the final assessment. RESULTS: Clinical efficacy achieved with cefovecin in dogs was equivalent to that observed with cefadroxil. At the final assessment, 14 days following the completion of treatment (on day 28 or 42), 92.4% (109/118) of the cefovecin group and 92.3% (108/117) of the cefadroxil group were treatment successes. There were no serious adverse events or deaths related to treatment. CONCLUSIONS AND CLINICAL RELEVANCE: A single cefovecin injection (8 mg/kg) administered SC, which could be repeated once after 14 days, was safe and effective against naturally occurring skin infections in dogs and as effective as cefadroxil administered PO twice daily for 14 or 28 days.