Pharmacokinetics of Intraperitoneal Cefalothin and Cefazolin in Patients Being Treated for Peritoneal Dialysis-Associated Peritonitis.

UNLABELLED: ♦ BACKGROUND: The standard treatment of peritoneal dialysis (PD)-associated peritonitis (PD-peritonitis) is intraperitoneal (IP) administration of antibiotics. Only limited data on the pharmacokinetics and appropriateness of contemporary dose recommendations of IP cefalothin and cefazolin exist. The aim of this study was to describe the pharmacokinetics of IP cefalothin and cefazolin in patients treated for PD-peritonitis. ♦ METHODS: As per international guidelines, IP cefalothin or cefazolin 15 mg/kg once daily was dosed with gentamicin in a 6-hour dwell to patients with PD-peritonitis during routine care. Serial plasma and PD effluent samples were collected over the first 24 hours of therapy. Antibiotic concentrations were quantified using a validated chromatographic method with pharmacokinetic analysis performed using a non-compartmental approach. ♦ RESULTS: Nineteen patients were included (cefalothin n = 8, cefazolin n = 11). The median bioavailability for both antibiotics exceeded 92%, but other pharmacokinetic parameters varied markedly between antibiotics. Both antibiotics achieved high PD effluent concentrations throughout the antibiotic dwell. Cefazolin had a smaller volume of distribution compared with cefalothin (14 vs 40 L, p = 0.003). The median trough total plasma antibiotic concentration for cefazolin and cefalothin during the dwell differed (plasma 56 vs 13 mg/L, p < 0.0001) despite a similar concentration in PD effluent (37 vs 38 mg/L, p = 0.58). Lower antibiotic concentrations were noted during PD dwells not containing antibiotic, particularly cefalothin, which was frequently undetectable in plasma and PD effluent. The median duration that the unbound antibiotic concentration was above the minimum inhibitory concentration (MIC) was approximately 13% (plasma) and 25% (IP) for cefalothin, and 100% (plasma and IP) for cefazolin, of the dosing interval. ♦ CONCLUSIONS: When IP cefalothin or cefazolin is allowed to dwell for 6 hours, sufficient PD effluent concentrations are present for common pathogens during this time. However, with once-daily IP dosing, in contrast to cefazolin, there is a risk of subtherapeutic plasma and PD effluent cefalothin concentrations, so more frequent dosing may be required.

High complication rate after syndesmotic screw removal.

PURPOSE: The aim of this study was to determine the rate of complications after routine syndesmotic screw removal. MATERIALS AND METHODS: All patients who underwent syndesmotic screw removal at our hospital between 2007 and 2012 were included in the study. Patient demographics, surgical characteristics, radiographic evaluation and complications were recorded from the patients' charts. Questionnaires were sent by postal mail to all patients, to measure patient satisfaction and pain (VAS scales). RESULTS: 161 patients were included in the trial. A wound infection was found in 8 (5%) patients. 3 were regarded as serious infections requiring hospitalisation and intravenous antibiotics, 2 of those required surgical revisions. 5 patients were treated by oral antibiotics. Staphylococcus aureus was identified as the causing organism in all (6/8) cases with a positive culture. The patients with postoperative infection reported more pain (5.3 vs. 2.3; p=0.02) and were less satisfied (4.7 vs. 7.6; p=0.014) with their ankle compared to those without infection (T-test for independent samples). CONCLUSION: There were 5% wound infections after routine syndesmotic screw removal. Routine antibiotic prophylaxis effective against S. aureus should be administered when removing syndesmotic screws. In our institution we now use one single dose Cefalotin of 2g intravenously 30-60min before screw removal.

Abiotrophia defectiva bleb-associated endophthalmitis confirmed with 16s ribosomal RNA sequencing.

One recognized complication of trabeculectomy with visually devastating potential is blebitis. We present a case of a 74-year-old woman with a culture and polymerase chain reaction-positive Abiotrophia defectiva bleb-associated endophthalmitis. Abiotrophia defectiva is a rare but possible cause of endophthalmitis secondary to blebitis and should be considered in culture-negative cases. Prompt identification, hence directed eradication, of the causative organism in such visually threatening cases may be facilitated by requesting polymerase chain reaction and 16S ribosomal RNA sequencing.

Oxacillin or cefalotin treatment of hospitalized children with cellulitis.

Cellulitis is an important cause of hospitalization in pediatrics. Because Staphylococcus aureus is the main pathogen of cellulitis, medicinal therapeutics should take the changing resistance profile of this organism into consideration. The aim of this study was to evaluate the progression and outcomes of children hospitalized for cellulitis and treated with oxacillin or cefalotin. This retrospective cohort study enrolled 218 children, hospitalized between 2001 and 2008 in Salvador, Northeast Brazil. All were diagnosed with cellulitis and treated with oxacillin or cefalotin (≥100 mg/kg/day). The median age was 2 years and 56.9% were males. Frequencies of signs and symptoms used in the clinical diagnoses were as follows: swelling (91.3%), redness (81.7%), warmth (47.2%), and tenderness (31.7%). All patients were discharged due to clinical recovery and the mean length of hospitalization was 7 ± 4 days. None of the patients died, needed intensive care, or had sequelae. By comparing the daily frequency of clinical findings during hospitalization, significant decreases were found in the frequencies of fever (admission day [42.2%], first day [20.8%], second day [12.9%], third day [8.3%], fourth day [6.1%]), toxemia, irritability, somnolence, vomiting, tachycardia, and need for intravenous hydration. In conclusion, oxacillin or cefalotin remain the drugs of choice for treating uncomplicated cellulitis in regions where community-acquired methicillin-resistant S. aureus is infrequent (<10%).

Neonatal Listeria-meningitis in San Luis, Argentina: a three-case report.

Between November 1996 and December 2006, two cases of early-onset and one case of late-onset neonatal listeriosis were reported in San Luis, Argentina. This article describes clinical and laboratory findings as well as treatment and outcome for newborns treated for Listeria monocytogenes meningitis or septicaemia. In one of the newborns with early-onset listeriosis, meningitis led to important complications including hydrocephalus. The two other newborns showed complete recovery following adequate treatment. The L. monocytogenes isolates from two patients belonged to PCR group IVb (including serovar 4b strains) and to PCR group IIb (including serovar 1/2b strains) in the third patient. Listeriosis, especially the maternal-fetal presentation, is still rare in Argentina for unknown reasons. Our data can be used in the future as an epidemiological survey.

Co-loading of bisphosphonates and antibiotics to a biomimetic hydroxyapatite coating.

We have incorporated bisphosphonates and antibiotics simultaneously into a biomimetic hydroxyapatite implant coating aiming to use the interaction between drug-molecules and hydroxyapatite to enable local release of the two different substances to obtain a dual biological effect. A sustained release over for 43 h of antibiotics (cephalothin) was achieved without negative interference from the presence of the bisphosphonate (clodronate) which, in turn, successfully bonded to the coating surface. To our knowledge, this is the first study that indicates the possibility to simultaneously incorporate both antibiotics and bisphosphonates to an implant coating, a strategy that is believed to improve implant stability and reduce implant-related infections.

The role of antibiotics in reduction mammaplasty.

This prospective study was conducted to assess the influence of antibiotics use on surgical site infections (SSI) rates after reduction mammaplasty. Patients undergoing reduction mammaplasty were assigned to group 1 (n = 50), which received intravenous cephalotin pre- and postoperatively, besides oral cephalexin for 6 days after discharge, or to group 2 (n = 50), which received no antibiotics. Patients were followed up weekly for 30 days, regarding to SSI, by a blinded surgeon. The Centers for Disease Control and Prevention definitions and classification of SSI were adopted. There was no statistical difference between the groups in regard to age, body mass index, duration of operation, and total resection weight. SSI rates were 2% and 14% in groups 1 and 2, respectively (P = 0.03). In group 2, older patients and those with higher resection weight had significant higher SSI rates (P = 0.02 and P = 0.04, respectively). We observed that antibiotics use decreased SSI rates after reduction mammaplasty.

A antibioticoprofilaxia nos diferentes tipos de parto / Antibiotic prophylaxis in different types of delivery

A antibioticoprofilaxia durante o ciclo gravídico-puerperal é claramente distinta do uso de antibióticos para tratamento de infecções estabelecidas e, frequentemente, é prescrita em bases empíricas. Devido ao uso disseminado dos antibióticos e à emergência de cepas resistentes, associada ao aumento da virulência bacteriana, os autores realizaram uma revisão sistemática com o objetivo de analisar as indicações da profilaxia antibiótica nos diferentes tipos de parto

The use of prophylactic antibiotics during pregnancy and the puerperium is clearly different from the use of antibiotics in the treatment of established infections and is frequently prescribed on empiric basis. Because of the widespread use of antibiotics and the emergence of resistant strains of common bacteria, associated with the increased bacterial virulence, the authors carried out a systematic review in order to analyze the administration of prophylactic antibiotics in different types of delivery

Increased incidence of postoperative infections during prophylaxis with cephalothin compared to doxycycline in intestinal surgery.

BACKGROUND: The antibiotics used for prophylaxis during surgery may influence the rate of surgical site infections. Tetracyclines are attractive having a long half-life and few side effects when used in a single dose regimen. We studied the rate of surgical site infections during changing regimens of antibiotic prophylaxis in medium and major size surgery. METHODS: Prospective registration of surgical site infection following intestinal resections and hysterectomies was performed. Possible confounding procedure and patient related factors were registered. The study included 1541 procedures and 1489 controls. The registration included time periods when the regimen was changed from doxycycline to cephalothin and back again. RESULTS: The SSI in the colorectal department increased from 19% to 30% (p=0.002) when doxycycline was substituted with cephalothin and decreased to 17% when we changed back to doxycycline (p=0.005). In the gynaecology department the surgical site infection rate did not increase significantly. Subgroup analysis showed major changes in infections in rectal resections from 20% to 35% (p=0.02) and back to 12% (p=0.003). CONCLUSION: Doxycycline combined with metronidazole, is an attractive candidate for antibiotic prophylaxis in medium and major size intestinal surgery.

[Comparison between two antibiotic schemes in relation to surgical site infection in children: a randomized clinical trial].

BACKGROUND: There are few randomized clinical trials that prove the effectiveness of antibiotic prophylaxis (AP) to prevent pediatric surgical site infections (SSI). We undertook this study to determine the effectiveness of AP vs. traditional scheme of antibiotics. METHODS: We carried out a randomized clinical trial at the General Surgery Department of a Tertiary Care Children's Hospital in Mexico City. There were 187 consecutive patients, age 18 years or less, with clean or clean-contaminated procedures performed between January 2005 and December 2006. Exclusion criteria included previous scar on operated site, receiving antibiotics, or no informed consent. Cefalotin or clindamycin plus amikacin was administered 2 h before incision, continued for just 24 h in the experimental group (EG) vs. cefalotin or clindamycin plus amikacin administered just before, during or after incision and continuing for 5 days (control group, CG). RESULTS: Sixteen patients were excluded. EG included 26 clean and 54 clean-contaminated procedures, and in the CG there were 27 and 64 procedures, respectively. EG had a lower incidence of SSI (1/80 [1.2 %] vs. 10/91 [10.9 %], RR 9.7, (95% CI: 1.2-77.9, p = 0.009). The difference is based mainly on the clean-contaminated procedures. CONCLUSIONS: AP administered 2 h before incision and continuing for 24 h significantly decreases the risk of SSI compared to CG in clean-contaminated procedures.

Protective effect of topical antibiotics in breast augmentation.

BACKGROUND: Previous studies indicate that antibacterial lavage and/or use of topical antibiotics may reduce infection in breast implant surgery and perhaps also reduce occurrence of capsular contracture. A retrospective analysis was performed to evaluate this effect. METHODS: The study participants included all women (n = 436) who underwent breast augmentation during two different time periods: 2000 to 2002 (n = 218) and 2005 to 2007 (n = 218). During the first period (2000 to 2002), cephalothin (Keflin), was added to the saline/epinephrine solution, which was used to irrigate the implant pocket and filled into the outer lumen of the saline/gel implants. In the second period (2005 to 2007), only saline/epinephrine was used. All women were operated on at the same clinic and by the same surgeon. Recorded postoperative complications included occurrence of infection, seroma, and capsular contracture. RESULTS: Medical records were identified for 414 women (94.9 percent): 2000 to 2002 (n = 203) and 2005 to 2007 (n = 211); 99.8 percent of all implants were placed in the submuscular position and 99.8 percent of all incisions were periareolar. Frequency of infection in the 2005 to 2007 cohort (12.8 percent) exceeded substantially the frequency among the 2000 to 2002 cohort (6.7 percent; p = 0.044), as did the frequency of seroma (7.6 percent versus 2.9 percent, respectively; p = 0.036). There was no significant difference in development of capsular contraction between the two groups (8.1 percent versus 5.9 percent; p = 0.393). CONCLUSION: The authors' data support the use of topical antibiotics in cosmetic breast surgery, because significant increases of both infections and seroma were seen in patients not treated with topical antibiotics compared with a cohort of similar patients where topical antibiotics were used.

Comparación de dos esquemas antibióticos en infección de sitio quirúrgico en niños / Comparison between two antibiotic schemes in relation to surgical site infection in children: a randomized clinical trial

Introducción: Hay pocos estudios controlados que prueben la efectividad de la profilaxis antibiótica para prevenir infección de sitio quirúrgico en niños. El objetivo de esta investigación es determinar la efectividad de la profilaxis antibiótica contra esquema tradicional de antibióticos. Material y métodos: Ensayo clínico controlado llevado a cabo en el Departamento de Cirugía General en hospital pediátrico de tercer nivel, de 187 casos consecutivos menores de 18 años, con herida limpia o limpia-contaminada, entre enero de 2005 y diciembre de 2006. Se excluyeron los pacientes con cicatriz previa, quienes habían recibido antibióticos o que no proporcionaron su consentimiento informado. A un grupo (experimental) se administró cefalotina o clindamicina más amikacina dos horas antes de la incisión y por 24 horas y a otro se le administraron los mismos antibióticos durante o después de incisión y por cinco días. Se determinó el número de infecciones de sitio quirúrgico en procedimientos limpios y limpios contaminados. Resultados: Se excluyeron 16 pacientes. El grupo experimental incluyó 26 procedimientos limpios y 54 limpios contaminados y el grupo control, 27 y 64, respectivamente. El grupo experimental tuvo menos incidencia de infección de sitio quirúrgico (1 de 80 [1.2 %] contra 10 de 91 [10.9 %]), RR = 9.7, IC 95 % = 1.2-77.9, p = 0.009. Dicha diferencia basada en los procedimientos limpios contaminados. Conclusiones: La profilaxis antibiótica administrada dos horas antes de incidir y por 24 horas disminuyó significativamente la incidencia de infección de sitio quirúrgico en heridas limpias contaminadas.

BACKGROUND: There are few randomized clinical trials that prove the effectiveness of antibiotic prophylaxis (AP) to prevent pediatric surgical site infections (SSI). We undertook this study to determine the effectiveness of AP vs. traditional scheme of antibiotics. METHODS: We carried out a randomized clinical trial at the General Surgery Department of a Tertiary Care Children's Hospital in Mexico City. There were 187 consecutive patients, age 18 years or less, with clean or clean-contaminated procedures performed between January 2005 and December 2006. Exclusion criteria included previous scar on operated site, receiving antibiotics, or no informed consent. Cefalotin or clindamycin plus amikacin was administered 2 h before incision, continued for just 24 h in the experimental group (EG) vs. cefalotin or clindamycin plus amikacin administered just before, during or after incision and continuing for 5 days (control group, CG). RESULTS: Sixteen patients were excluded. EG included 26 clean and 54 clean-contaminated procedures, and in the CG there were 27 and 64 procedures, respectively. EG had a lower incidence of SSI (1/80 [1.2 %] vs. 10/91 [10.9 %], RR 9.7, (95% CI: 1.2-77.9, p = 0.009). The difference is based mainly on the clean-contaminated procedures. CONCLUSIONS: AP administered 2 h before incision and continuing for 24 h significantly decreases the risk of SSI compared to CG in clean-contaminated procedures.

Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release.

The possibility to fast-load biomimetic hydroxyapatite coatings on surgical implant with the antibiotics Amoxicillin, Gentamicin sulfate, Tobramycin and Cephalothin has been investigated in order to develop a multifunctional implant device offering sustained local anti-bacterial treatment and giving the surgeon the possibility to choose which antibiotics to incorporate in the implant at the site of surgery. Physical vapor deposition was used to coat titanium surfaces with an adhesion enhancing gradient layer of titanium oxide having an amorphous oxygen poor composition at the interface and a crystalline bioactive anatase TiO(2) composition at the surface. Hydroxyapatite (HA) was biomimetically grown on the bioactive TiO(2) to serve as a combined bone in-growth promoter and drug delivery vehicle. The coating was characterized using scanning and transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The antibiotics were loaded into the HA coatings via soaking and the subsequent release and antibacterial effect were analyzed using UV spectroscopy and examination of inhibition zones in a Staphylococcus aureus containing agar. It was found that a short drug loading time of 15 min ensured antibacterial effects after 24 h for all antibiotics under study. It was further found that the release processes of Cephalothin and Amoxicillin consisted of an initial rapid drug release that varied unpredictably in amount followed by a reproducible and sustained release process with a release rate independent of the drug loading times under study. Thus, implants that have been fast-loaded with drugs could be stored for ~10 min in a simulated body fluid after loading to ensure reproducibility in the subsequent release process. Calculated release rates and measurements of drug amounts remaining in the samples after 22 h of release indicated that a therapeutically relevant dose could be achieved close to the implant surface for about 2 days. Concluding, the present study provides an outline for the development of a fast-loading slow-release surgical implant kit where the implant and the drug are separated when delivered to the surgeon, thus constituting a flexible solution for the surgeon by offering the choice of quick addition of antibiotics to the implant coating based on the patient need.

Inadequate antimicrobial prophylaxis during surgery: a study of beta-lactam levels during burn debridement.

OBJECTIVES: To determine how long single-dose prophylactic antibiotic regimens for burns surgery maintained plasma concentrations above the MICs for target organisms during surgery. PATIENTS AND METHODS: We monitored antibiotic plasma concentrations in 12 patients (mean +/- SD 43 +/- 12% total burn surface area) throughout debridement surgery after administration of the standard prophylactic antibiotic dosing regimens of either 1 g of intravenous cefalotin or 4.5 g of intravenous piperacillin/tazobactam. RESULTS: The eschar debridement and grafting procedures ranged in duration from 2.25 to over 8.5 h. The duration of total plasma cefalotin concentration above an MIC of 0.2 mg/L for Staphylococcus aureus was 6.49 +/- 2.85 h, whereas the mean duration of total plasma piperacillin concentration above an MIC of 64 mg/L for Pseudomonas aeruginosa was only 1.15 +/- 0.59 h. None of the patients dosed with piperacillin/tazobactam was adequately protected for the duration of their surgery and adequate prophylaxis was only evident in four of the nine patients administered cefalotin. CONCLUSIONS: These results suggest a need to review antibiotic prophylaxis dosage regimens for burns surgery and the adoption of regimens that will minimize the risk of infection in this high-risk patient group. It is suggested that the antibiotic prophylaxis guideline for burn debridement surgery be modified to include re-dosing or a continuous infusion of beta-lactam antibiotics.

Randomized controlled trial on prevention of postcesarean infection using penicillin and cephalothin in Brazil.

BACKGROUND: There is a need to assess the effects of different antibiotic administration models on infectious complications among women from low-income populations who undergo cesarean delivery, and the cost benefit. DESIGN: Randomized, blinded controlled clinical trial study of a single preoperative dose of cephalothin, versus a postcesarean scheme for infection prophylaxis, versus no antibiotics. METHODS: The setting was a tertiary Brazilian center with 1,500 deliveries annually. Pregnant women (n = 600) with an indication for emergency or elective cesarean section were randomly allocated consecutively to one of three groups and treated as follows: Group 1 (n = 200), no antibiotics; Group 2 (n = 200), the standard antibiotics scheme followed at this center; Group 3 (n = 200), a single dose of intravenous cephalothin 2 g, intraoperatively. MAIN OUTCOME MEASUREMENTS: Prevalences of wound infection, puerperal and postcesarean infections, and costs of antibiotics used. RESULTS: Antibiotics reduced the incidence of puerperal infection, but did not change the percentages of wound and postcesarean infections and no use of antibiotics increased the puerperal infection risk sixfold. Cephalothin reduced the relative risk of puerperal infection by 89% (95% confidence interval: 7-87%). Penicillin reduced it by 78%, but this was not statistically significant. No deaths occurred. The costs of the two schemes were similar (almost US 1.00 dollars). CONCLUSIONS. Prophylactic cephalothin use was associated with decreased postcesarean puerperal infection and presented a cost benefit.