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.

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.

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

An audit of first generation cephalosporin usage.

Cefadroxil is a semi-synthetic first generation oral cephalosporin with advantages of almost 100% excretion in the urine within six hours and low cost. It was freely available in the formulary and we undertook an audit of its usage, the indications cited, underlying clinical conditions and relevant microbiology in 106 cases. Following the audit, cefadroxil was restricted, available only on the advice of a microbiologist. Subsequently, another survey was carried out to document the reasons for requesting cefadroxil by clinical staff and the alternatives suggested in each case. The first survey revealed that in 91% cases, cefadroxil had been used inappropriately. The second suggested that the reasons for requesting it were based upon misunderstanding by clinicians as to its value. The only useful indication identified was the treatment of susceptible bacteruria in pregnancy. A suitable oral alternative could be identified for all other cases where an antibiotic was indicated. We believe that first generation cephalosporins such as cefadroxil have little role in hospital practice and should therefore be restricted.

[Current role of aminoglycosides in the treatment of acute pyelonephritis]. / Place actuelle des aminoglycosides dans le traitement des pyélonéphrites aiguës.

In view of the very great efficacy of 3rd generation cephalosporins and fluoroquinolones used as monotherapy in the treatment of uncomplicated acute pyelonephritis, the addition of an aminoglycoside is not currently recommended, because of the unfavourable balance of the advantages and disadvantages of this antibiotic class. However, a brief course of aminoglycosides may nevertheless be useful during the initial phase of treatment, especially in hospitalised subjects. The authors analyse the contribution of three recently published studies to this debate.

Tumescent technique for local anesthesia improves safety in large-volume liposuction.

The tumescent technique for local anesthesia improves the safety of large-volume liposuction ( > or = 1500 ml of fat) by virtually eliminating surgical blood loss and by completely eliminating the risks of general anesthesia. Results of two prospective studies of large-volume liposuction using the tumescent technique are reported. In 112 patients, the mean lidocaine dosage was 33.3 mg/kg, the mean volume of aspirated material was 2657 ml, and the mean volume of supernatant fat was 1945 ml. The mean volume of whole blood aspirated by liposuction was 18.5 ml. For each 1000 ml of fat removed, 9.7 ml of whole blood was suctioned. In 31 large-volume liposuction patients treated in 1991, the mean difference between preoperative and 1-week postoperative hematocrits was -1.9 percent. The last 87 patients received no parenteral sedation. In a second study, a 75-kg woman received 35 mg/kg of lidocaine on two separate occasions, first without liposuction and 25 days later with liposuction; peak plasma lidocaine concentrations occurred at 14 and 11 hours after beginning the infiltration and were 2.37 and 1.86 micrograms/ml, respectively.

[Treatment and surgery of abdominal septic states: comparison of two antibiotic therapies]. / Traitement et chirurgie de l'état septique abdominal: étude comparative de deux antibiothérapies.

A prospective, randomized controlled study was carried out in 104 patients to compare clavulanate-potentiated amoxycillin ('Augmentin') with a combination of cephalosporins (cefazoline and cefadroxil) supplemented with metronidazole in the treatment of abdominal septic states, suspected or proven after surgical intervention. Patients on 'Augmentin' received 1.2 g (1 g amoxycillin plus 200 mg clavulanic acid) intravenously 3-times daily for a mean of 6.6 days, then 375 mg (250 amoxycillin plus 125 mg clavulanic acid) orally for a further 6.4 days. Patients on the standard therapy received 1 g cefazoline intravenously 4-times daily plus 500 mg metronidazole intravenously 3-times daily for 7 days, then 500 mg cefadroxil orally 4-times daily for a mean of 6.6 days. Evaluation of the patients' condition was undertaken after 24 hours, 3 days and 7 days. The results showed a significantly better response to treatment in the 'Augmentin' group, as judged by the amelioration of clinical symptoms, bacteriological findings, and tolerance. All the patients treated with 'Augmentin' showed an excellent or satisfactory overall response at Day 7 compared with 76% of those receiving the standard therapy.

[Treatment of urinary infection with cephadroxyl (Pharmachem)--microbiological and clinical research]. / Lechenie na uroinfektsiiata s tsefadroksil (Farmakhim)--mikrobiologichni i klinichni prouchvaniia.

The bacteria isolated from the urine of renal patients were tested for sensitivity towards cephadroxyl (Pharmachem) and other beta-lactam antibiotics--altogether 654 examinations were made. It was established that the gram-positive bacteria (excluding the Enterococcus) are sensitive towards cephadroxyl. From the Gram negative bacteria E. Coli, Klebsiella sp., Enterobacter sp., P. mirabilis, Citrobacter sp. showed the greatest sensitivity towards cephadroxyl, while the indole positive Proteus were with low sensitivity and P. aeruginosa, Acinetobacter sp., Serratia were resistant towards cephadroxyl. 30 patients with persistent mainly secondary urinary infection were treated with cephadroxyl. The clinical symptoms disappeared in 63.3% of the patients and another 26.7% of them showed considerable improvement. Bacteriological sterility of the urine was achieved in 61.29% of the patients. The side effects were mild and rare, only in single cases.

Therapeutic efficacy of cefadroxil and cephalexin for pneumonia in a rat test model.

The therapeutic efficacies of cefadroxil and cephalexin were compared in a Streptococcus pyogenes-induced lung infection in rats. Although MICs, rates of in vitro killing in rat serum, and antibiotic serum levels after oral administration were similar for both drugs, cefadroxil was about eight times more effective than cephalexin in reducing the number of viable streptococci at the site of infection. This excellent in vivo bactericidal activity of cefadroxil in lung tissue and bronchial secretions was reflected in the 50% protective dose (PD50) after single or multiple oral treatments. A single treatment given 24 h after infection resulted in a PD50 of 2.8 mg of cefadroxil per kg, compared with 21 mg of cephalexin per kg. When treatment was administered three times, at 24, 27, and 30 h postinfection, the PD50s of cefadroxil and cephalexin were 0.7 and 8.0 mg/kg, respectively. In infected animals, treated 24 h postinfection, the area under the lung tissue concentration versus time curve for cefadroxil was significantly greater than that of cephalexin. This difference in pharmacokinetic behavior may account, at least in part, for the superior therapeutic results obtained with cefadroxil in this experimental pulmonary infection.

Efficacy of a twice-daily regimen of cefadroxil in the treatment of respiratory tract infections.

This multicentre open study evaluated the responses of 474 adult and paediatric patients with upper or lower respiratory tract infections to treatment with cefadroxil (25 to 50 mg/kg in children and 500 mg to 1 g in adults) twice daily for 10 to 30 days. Complete or partial cures seen in 81% to 100% of all patients correlated with the eradication of 87% to 100% of the causative pathogens, most commonly beta-haemolytic streptococci, S. aureus or S. pneumoniae. Mild, transient side effects, usually gastrointestinal disturbances or hypersensitivity reactions, were reported in 4.8% of patients. Thus, the safety and efficacy of this oral cephalosporin recommends its use in the treatment of infections of the respiratory tract.

A comparative study of cefadroxil and co-trimoxazole in patients with lower respiratory tract infections.

The most common causative pathogens in lower respiratory disease are S. pneumoniae, H. influenzae and S. pyogenes. Cefadroxil and co-trimoxazole, both orally administered broad spectrum antibiotics, are effective against these organisms when given in a twice-daily regimen. In this open randomised study, 42 patients with lower respiratory tract infections received cefadroxil 1 g or co-trimoxazole 1 double-strength tablet every 12 hours for a mean duration of 11 and 13 days, respectively. Pathogens were isolated in the pre-treatment sputum of 51% of patients given cefadroxil and in 25% of those who received co-trimoxazole. Similar overall cure rates were observed after treatment with cefadroxil (67%) and co-trimoxazole (60%); sputum purulence was similarly diminished by both drugs (91% and 85%, respectively). Neither antibiotic caused serious side effects. Thus, in a convenient twice-daily regimen, cefadroxil and co-trimoxazole are comparably effective in treating lower respiratory tract infections.