Dose regimen optimization of cephalothin for surgical prophylaxis against Staphylococcus aureus and coagulase negative staphylococci in dogs by pharmacokinetic/pharmacodynamic modeling.

First generation cephalosporins such cephalothin of cefazolin are indicated for antimicrobial prophylaxis for clean and clean contaminated surgical procedures because its antimicrobial spectrum, relative low toxicity and cost. Anesthesia and surgery could alter the pharmacokinetic behavior of different drugs administered perioperative by many mechanisms that affect distribution, metabolism or excretion processes. Intravenous administration of the antimicrobial within 30 and 60 min before incision is recommended in order to reach therapeutic serum and tissue concentrations and redosing is recommended if the duration of the procedure exceeds two half-life of the antimicrobial. To the author's knowledge there are no pharmacokinetic studies of cephalothin in dogs under anesthesia/surgery conditions. The aim of this study was (1) to evaluate the pharmacokinetics of cephalothin in anesthetized dogs undergoing ovariohysterectomy by a nonlinear mixed-effects model and to determine the effect of anesthesia/surgery and other individual covariates on its pharmacokinetic behavior; (2) to determine the MIC and conduct a pharmacodynamic modeling of time kill curves assay of cephalothin against isolates of Staphylococcus spp. isolated from the skin of dogs; (3) to conduct a PK/PD analysis by integration of the obtained nonlinear mixed-effects models in order to evaluate the antimicrobial effect of changing concentrations on simulated bacterial count; and (4) to determine the PK/PD endpoints and PK/PDco values in order to predict the optimal dose regimen of cephalothin for antimicrobial prophylaxis in dogs. Anesthesia/surgery significantly reduced cephalothin clearance by 18.78%. Based on the results of this study, a cephalothin dose regimen of 25 mg/kg q6h by intravenous administration showed to be effective against Staphylococcus spp. isolates with MIC values ≤2 µg/mL and could be recommended for antimicrobial prophylaxis for clean surgery in healthy dogs.

Disc Test for Detecting Staphylococcus aureus Strains Producing Type A and Type C ß-Lactamases.

Staphylococcus aureus can produce ß-lactamases capable of hydrolyzing penicillins and first-generation cephalosporins. The propensity of type A and type C ß-lactamase-producing S. aureus (TAPSA and TCPSA) to hydrolyze cefazolin at a high inoculum is termed the cefazolin inoculum effect (CIE). Strains with a CIE have a theoretical risk of causing treatment failure and are unable to be detected routinely by most laboratories. We developed a high-performing yet straightforward ß-lactamase disc test that identifies and differentiates both TAPSA and TCPSA and is suitable for routine diagnostic laboratory workflows. Clinical isolates of S. aureus resistant to penicillin were identified, and their blaZ genes were sequenced. MICs were determined at low and high inocula (5 × 105 CFU/mL and 5 × 107 CFU/mL), and isolates demonstrating a CIE were characterized. A semimechanistic model was established to describe differential hydrolysis patterns, and candidate models were iteratively assessed using area-under-the-curve analysis from competitor receiver operating characteristic (ROC) curves. Biomarker thresholds were derived from Youdon index-derived optimal cutoff values. Genetic analysis of 99 isolates identified 26 TAPSA isolates and 45 TCPSA isolates. The model best differentiating TAPSA from non-TAPSA utilized cefazolin-to-cephalothin ratio analysis (sensitivity, 96.2%; specificity, 98.6%). The model best differentiating TCPSA from non-TCPSA incorporated cefazolin, cephalothin, and oxacillin (sensitivity, 88.6%; specificity, 96.6%). TAPSA and TCPSA can be differentiated using three antibiotic discs on a single agar plate. The test has potential value in typing the ß-lactamase type from isolates from patients that are candidates for or have failed cefazolin therapy. IMPORTANCE The key significance of this article is that it details a straightforward method of performing a disc test that can differentiate Staphylococcus aureus isolates that are likely to be associated with a cefazolin inoculum effect and theoretical risk of cefazolin treatment failure from isolates that are less likely to be associated with a cefazolin inoculum effect.

Analysis of the Antimicrobial and Anti-Biofilm Activity of Natural Compounds and Their Analogues against Staphylococcus aureus Isolates.

(1) Background: Staphylococcus aureus (S. aureus) is one of the most frequent causes of biofilm-associated infections. With the emergence of antibiotic-resistant, especially methicillin-resistant S. aureus (MRSA), there is an urgent need to discover novel inhibitory compounds against this clinically important pathogen. In this study, we evaluated the antimicrobial and anti-biofilm activity of 11 compounds, including phenyl propenes and phenolic aldehydes, eugenol, ferulic acid, sinapic acid, salicylaldehyde, vanillin, cinnamoyl acid, and aldehydes, against drug-resistant S. aureus isolates. (2) Methods: Thirty-two clinical S. aureus isolates were obtained from Alkhidmat Diagnostic Center and Blood Bank, Karachi, Pakistan, and screened for biofilm-forming potential, and susceptibility/resistance against ciprofloxacin, chloramphenicol, ampicillin, amikacin, cephalothin, clindamycin, streptomycin, and gentamicin using the Kirby-Bauer disk diffusion method. Subsequently, 5 representative clinical isolates were selected and used to test the antimicrobial and anti-biofilm potential of 11 compounds using both qualitative and quantitative assays, followed by qPCR analysis to examine the differences in the expression levels of biofilm-forming genes (ica-A, fnb-B, clf-A and cna) in treated (with natural compounds and their derivatives) and untreated isolates. (3) Results: All isolates were found to be multi-drug resistant and dominant biofilm formers. The individual Minimum Inhibitory Concentration (MIC) of natural compounds and their analogues ranged from 0.75−160 mg/mL. Furthermore, the compounds, Salicylaldehyde (SALI), Vanillin (VAN), α-methyl-trans-cinnamaldehyde (A-MT), and trans-4-nitrocinnamic acid (T4N) exhibited significant (15−92%) biofilm inhibition/reduction percentage capacity at the concentration of 1−10 mg/mL. Gene expression analysis showed that salicylaldehyde, α-methyl-trans-cinnamaldehyde, and α-bromo-trans-cinnamaldehyde resulted in a significant (p < 0.05) downregulation of the expression of ica-A, clf-A, and fnb-A genes compared to the untreated resistant isolate. (4) Conclusions: The natural compounds and their analogues used in this study exhibited significant antimicrobial and anti-biofilm activity against S. aureus. Biofilms persist as the main concern in clinical settings. These compounds may serve as potential candidate drug molecules against biofilm forming S. aureus.

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.

Postoperative Antibiotic Prophylaxis in Reduction Mammaplasty: A Randomized Controlled Trial.

BACKGROUND: Reduction mammaplasty is a well-established procedure. Studies have shown benefits of using antibiotics in this procedure. Nevertheless, there is no solid evidence to support postoperative antibiotic prophylaxis. The authors evaluated the influence of postoperative antibiotic delivery on infection rates after reduction mammaplasty. METHODS: The authors conducted a randomized trial of noninferiority, with two parallel groups, with triple blinding. The participants were 124 women with breast hypertrophy, with reduction mammaplasty already scheduled, selected consecutively. All patients underwent reduction mammaplasty, performed by the same surgical team, using the superomedial pedicle technique for ascending the nipple-areola complex. All patients received cephalothin (1 g) intravenously at the anesthetic induction and every 6 hours for 24 hours. At hospital discharge, they were assigned randomly to either the placebo (n = 62) or antibiotic group (n = 62) and were instructed to take identical capsules containing 500 mg of cephalexin or placebo, respectively, every 6 hours, for 7 days. Patients were assessed weekly, for 4 weeks, regarding the occurrence of surgical-site infection, by a surgeon who was unaware of the allocation. The criteria and definitions of the Centers for Disease Control and Prevention were adopted. RESULTS: There was no statistical difference between groups regarding age, body mass index, or resected breast tissue weight. The overall surgical-site infection rate was 0.81 percent. Only one patient, allocated to the antibiotic, presented infection, classified as superficial incisional (p = 1.00). In the placebo group, surgery time was higher (p = 0.003). CONCLUSION: The maintenance of antibiotics in the postoperative period of reduction mammaplasty did not influence the rates of surgical-site infection. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Theaflavin-3,3´-digallate increases the antibacterial activity of ß-lactam antibiotics by inhibiting metallo-ß-lactamase activity.

Metallo-ß-lactamases (MBLs) are some of the best known ß-lactamases produced by common Gram-positive and Gram-negative pathogens and are crucial factors in the rise of bacterial resistance against ß-lactam antibiotics. Although many types of ß-lactamase inhibitors have been successfully developed and used in clinical settings, no MBL inhibitors have been identified to date. Nitrocefin, checkerboard and time-kill assays were used to examine the enzyme behaviour in vitro. Molecular docking calculation, molecular dynamics simulation, calculation of the binding free energy and ligand-residue interaction decomposition were used for mechanistic research. The behaviour of the enzymes in vivo was investigated by a mouse infection experiment. We showed that theaflavin-3,3´-digallate (TFDG), a natural compound lacking antibacterial activities, can inhibit the hydrolysis of MBLs. In the checkerboard and time-kill assays, we observed a synergistic effect of TFDG with ß-lactam antibiotics against methicillin-resistant Staphylococcus aureus BAA1717. Molecular dynamics simulations were used to identify the mechanism of the inhibition of MBLs by TFDG, and we observed that the hydrolysis activity of the MBLs was restricted by the binding of TFDG to Gln242 and Ser369. Furthermore, the combination of TFDG with ß-lactam antibiotics showed effective protection in a mouse Staphylococcus aureus pneumonia model. These findings suggest that TFDG can effectively inhibit the hydrolysis activity of MBLs and enhance the antibacterial activity of ß-lactam antibiotics against pathogens in vitro and in vivo.

Satisfacción de los pacientes con enfermedad de La Peyronie tras cirugía de placa e injerto de pericardio bovino / Satisfaction of patients with Peyronie's disease after plaque surgery and bovine pericardium graft

Introducción: La cirugía de placa e injerto de pericardio bovino es una herramienta útil en el tratamiento de la enfermedad de La Peyronie. Objetivo: Determinar la satisfacción de los pacientes tras la realización de esta cirugía. Materiales y métodos: Estudio retrospectivo, observacional y descriptivo. Se recabaron los datos de las historias clínicas de los pacientes operados entre 2004 y 2015, y fueron evaluados mediante un cuestionario de satisfacción postoperatoria. Resultados: Se realizaron 28 cirugías. La corrección de la curva se logró en 26 pacientes (95,3%). Un paciente (3,57%) requirió corrección de la curva residual mediante técnica de Yachia, y un paciente (3,57%) presentó una complicación grave consistente en infección protésica y fístula uretrocutánea. Veintiún pacientes (75%) se mostraron satisfechos con la cirugía. Conclusiones: Nuestros resultados muestran un aceptable nivel de satisfacción de nuestros pacientes con un bajo número de complicaciones, aunque se necesitan más trabajos, prospectivos, controlados y aleatorizados

Introduction: Plaque and bovine pericardium graft surgery is a useful tool for treating Peyronie's disease. Objective: To determine patient satisfaction following this operation. Materials and methods: This was a retrospective, observational and descriptive study. We collected data from the medical records of patients who underwent surgery between 2004 and 2015 and were evaluated through a postoperative satisfaction questionnaire. Results: Twenty-eight operations were performed. Curve correction was achieved in 26 patients (95.3%). One patient (3.57%) required residual curve correction using Yachia's technique, and 1 patient (3.57%) had a severe complication consisting of prosthetic infection and urethrocutaneous fistulae. Twenty-one patients (75%) expressed satisfaction with the surgery. Conclusions: Our results show an acceptable level of satisfaction among our patients, with a low number of complications. However, further prospective, controlled and randomised studies are needed

Eficacia del esquema de impregnación vs. esquema de mantenimiento con ceftazidima/cefalotina en pacientes con peritonitis por diálisis / Effectiveness of the scheme reimpregnation maintenance schedule vs. ceftazidime/cephalothin in dialysis patients with peritonitis

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Antibiotics for treating septic abortion.

BACKGROUND: A septic abortion refers to any abortion (spontaneous or induced) complicated by upper genital tract infection including endometritis or parametritis. The mainstay of treatment of septic abortion is antibiotic therapy alone or in combination with evacuation of retained products of conception. Regimens including broad-spectrum antibiotics are routinely recommended for treatment. However, there is no consensus on the most effective antibiotics alone or in combination to treat septic abortion. This review aimed to bridge this gap in knowledge to inform policy and practice. OBJECTIVES: To review the effectiveness of various individual antibiotics or antibiotic regimens in the treatment of septic abortion. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and POPLINE using the following keywords: 'Abortion', 'septic abortion', 'Antibiotics', 'Infected abortion', 'postabortion infection'. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 19 April, 2016. SELECTION CRITERIA: We considered for inclusion randomised controlled trials (RCTs) and non-RCTs that compared antibiotic(s) to another antibiotic(s), irrespective of route of administration, dosage, and duration as well as studies comparing antibiotics alone with antibiotics in combination with other interventions such as dilation and curettage (D&C). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included trials. We resolved disagreements through consultation with a third author. One review author entered extracted data into Review Manager 5.3, and a second review author cross-checked the entry for accuracy. MAIN RESULTS: We included 3 small RCTs involving 233 women that were conducted over 3 decades ago.Clindamycin did not differ significantly from penicillin plus chloramphenicol in reducing fever in all women (mean difference (MD) -12.30, 95% confidence interval (CI) -25.12 to 0.52; women = 77; studies = 1). The evidence for this was of moderate quality. "Response to treatment was evaluated by the patient's 'fever index' expressed in degree-hour and defined as the total quantity of fever under the daily temperature curve with 99°F (37.2°C) as the baseline".There was no difference in duration of hospitalisation between clindamycin and penicillin plus chloramphenicol. The mean duration of hospital stay for women in each group was 5 days (MD 0.00, 95% CI -0.54 to 0.54; women = 77; studies = 1).One study evaluated the effect of penicillin plus chloramphenicol versus cephalothin plus kanamycin before and after D&C. Response to therapy was evaluated by "the time from start of antibiotics until fever lysis and time from D&C until patients become afebrile". Low-quality evidence suggested that the effect of penicillin plus chloramphenicol on fever did not differ from that of cephalothin plus kanamycin (MD -2.30, 95% CI -17.31 to 12.71; women = 56; studies = 1). There was no significant difference between penicillin plus chloramphenicol versus cephalothin plus kanamycin when D&C was performed during antibiotic therapy (MD -1.00, 95% CI -13.84 to 11.84; women = 56; studies = 1). The quality of evidence was low.A study with unclear risk of bias showed that the time for fever resolution (MD -5.03, 95% CI -5.77 to -4.29; women = 100; studies = 1) as well as time for resolution of leukocytosis (MD -4.88, 95% CI -5.98 to -3.78; women = 100; studies = 1) was significantly lower with tetracycline plus enzymes compared with intravenous penicillin G.Treatment failure and adverse events occurred infrequently, and the difference between groups was not statistically significant. AUTHORS' CONCLUSIONS: We found no strong evidence that intravenous clindamycin alone was better than penicillin plus chloramphenicol for treating women with septic abortion. Similarly, available evidence did not suggest that penicillin plus chloramphenicol was better than cephalothin plus kanamycin for the treatment of women with septic abortion. Tetracyline enzyme antibiotic appeared to be more effective than intravenous penicillin G in reducing the time to fever defervescence, but this evidence was provided by only one study at low risk of bias.There is a need for high-quality RCTs providing reliable evidence for treatments of septic abortion with antibiotics that are currently in use. The three included studies were carried out over 30 years ago. There is also a need to include institutions in low-resource settings, such as sub-Saharan Africa, Latin America and the Caribbean, and South Asia, with a high burden of abortion and health systems challenges.

Problemas clínicos en micología médica: problema número 49 / Clinical problems in medical mycology: problem number 49

The case of a 59-year-old female born in Buenos Aires (Argentina) is presented. She had been diagnosed with HIV in 2007 and received highly active antiretroviral therapy until 2011; she also suffered from diabetes type 2. She had received empirical treatment (pyrimethamine-clindamycin) for cerebral toxoplasmosis. Fifteen days later she suffered a drug-induced skin disorder and was treated in the Dermatology Service of the Hospital Muñiz with corticosteroids. After five weeks she was readmitted to the Infectious Disease Unit due to asthenia, weight loss, left hip pain and weakness in all four limbs. Septic arthritis and aseptic hip necrosis were ruled out. Blood cultures were positive for Staphylococcus aureus and Escherichia coli. The patient received intravenous antibiotics, but before being discharged Acinetobacter baumannii was isolated from blood, catheter and urine cultures, and a new series of antibiotics were prescribed. On the 3rd day she presented encephalic facies, changes of behaviour and disorientation, without nuchal rigidity, Kernig and Brudzinski signs or focal signs. An X-ray computed tomography did not show parenchymal lesions. A yeast identified as Candida albicans was isolated in a cerebrospinal fluid culture. The same yeast was recovered in a new cerebrospinal fluid sample. The isolate was susceptible to amphotericin B and susceptible dose dependent to fluconazole. The patient was treated with amphotericin B (0.7 mg/kg plus 800 mg fluconazole daily). Three weeks later, new cerebrospinal fluid cultures were negative. Unfortunately, the patient died soon afterwards (AU)

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Cefalotin as antimicrobial prophylaxis in patients with known intraoperative anaphylaxis to cefazolin.

BACKGROUND: The most common trigger for intraoperative anaphylaxis in Western Australia for the period 2014-5 was an antibiotic used for surgical prophylaxis, cefazolin. In these patients who subsequently present for surgery, alternative cephalosporins are forbidden by current guidelines because of concerns regarding an increased risk of anaphylaxis. However, consideration of the structure-activity relationships relevant to anaphylaxis suggests that cefalotin is a safe alternative because of structural dissimilarities, although there are no pubished clinical data relevant to the perioperative setting. METHODS: Patients diagnosed with intraoperative anaphylaxis to cefazolin at the Western Australian Anaesthetic Allergy Clinic were tested with intradermal cefalotin and, if negative, subsequently challenged i.v. If tolerated, cefalotin was recommended for subsequent surgery, and subjects were followed up to determine the safety of subsequent intraoperative doses. RESULTS: Twenty-one subjects diagnosed with immediate hypersensitivity to cephazolin, including 19 subjects with confirmed anaphylaxis, participated. None tested positive to intradermal cefalotin, and all received a graded i.v. challenge to cefalotin without developing signs or symptoms of anaphylaxis. Three subjects subsequently received intraoperative cefalotin 12-139 days later without adverse events. CONCLUSIONS: A negative intradermal cefalotin skin test has a good negative predictive value in patients who have previously suffered anaphylaxis to cefazolin, allowing the rational and desirable use of this alternative cephalosporin for future surgery and the avoidance of less desirable antimicrobial agents.

Presence of AmpC beta-lactamases, CSA-1, CSA-2, CMA-1, and CMA-2 conferring an unusual resistance phenotype in Cronobacter sakazakii and Cronobacter malonaticus.

Here we describe the presence of two very similar but unusual variants of AmpC cephalosporinase in each Cronobacter sakazakii and C. malonaticus isolates conferring resistance exclusively to first generation cephalosporins. During a survey on the antibiotic resistance patterns of C. sakazakii and C. malonaticus strains isolated from a milk powder production facility, originally two different phenotypes regarding the susceptibility/resistance for the two beta-lactam antibiotics ampicillin (amp) and cephalothin (ceph) were observed: (i) isolates being susceptible for both antibiotics (amp(S)/ceph(S)), and (ii) strains exhibiting susceptibility to ampicillin but resistance to cephalothin (amp(S)/ceph(R)). The latter phenotype (amp(S)/ceph(R)) was observed in the majority of the environmental strains from the facility. Analysis of whole genome sequences of C. sakazakii revealed a gene putatively coding for an AmpC beta-lactamase. Consequently, the ampC genes from both species and both phenotypes were subjected to a cloning approach. Surprisingly, when expressed in Escherichia coli, all transformants exhibited the amp(S)/ceph(R) phenotype regardless of (i) the phenotypic backgrounds or (ii) the AmpC amino acid sequences of the original strains from which the clones were derived. The novel AmpC beta-lactamases were designated CSA-1 and CSA-2 (from C. sakazakii) and CMA-1 and CMA-2 (from C. malonaticus). The observed variations in the minimum inhibitory concentration (MIC) levels for cephalothin (wt compared to transformants) suggest that this feature is a target of a yet unknown regulatory mechanism present in the natural Cronobacter background but absent in the neutral E. coli host.

Bacteriuria amongst pregnant women in the Buea Health District, Cameroon: prevalence, predictors, antibiotic susceptibility patterns and diagnosis.

BACKGROUND: Bacteriuria is associated with significant maternal and foetal risks. However, its prevalence is not known in our community. OBJECTIVES: This study was carried out to determine the prevalence and predictors of bacteriuria in pregnant women of the Buea Health District (BHD) as well as the antibiotic sensitivity patterns of bacterial isolates. It also sought to determine the diagnostic performance of the nitrite and leucocyte esterase tests in detecting bacteriuria in these women. METHODS: An observational analytic cross-sectional study was carried out amongst pregnant women attending selected antenatal care centres in Buea. We recruited 102 consenting pregnant women for the study. Demographic and clinical data were collected using structured questionnaires. Clean catch midstream urine was collected from each participant in sterile leak proof containers. Samples were examined biochemically, microscopically and by culture. Significant bacteriuria was defined as the presence of ≥108 bacteria/L of cultured urine. Identification and susceptibility of isolates was performed using API 20E and ATB UR EU (08) (BioMerieux, Marcy l'Etoile, France). RESULTS: Significant bacteriuria was found in the urine of 24 of the 102 women tested giving a bacteriuria prevalence of 23.5% in pregnant women of the BHD. Asymptomatic bacteriuria was detected in 8(7.8%) of the women. There was no statistically significant predictor of bacteriuria. Escherichia coli were the most isolated (33%) uropathogens and were 100% sensitive to cefixime, cefoxitin and cephalothin. The nitrite and leucocyte esterase tests for determining bacteriuria had sensitivities of 8%, 20.8% and specificities of 98.7% and 80.8% respectively. CONCLUSION: Bacteriuria is frequent in pregnant women in the BHD suggesting the need for routine screening by urine culture. Empiric treatment with cefixime should be instituted until results of urine culture and sensitivity are available. Nitrite and leucocyte esterase tests were not sensitive enough to replace urine culture as screening tests.

Comparación de concentración mínima inhibitoria y concentración plasmática de cefalotina mediante un modelo matemático / Comparison of the minimal inhibitory concentration and the plasma cephalotin concentration through a mathematical model

Introducción: el uso de fármacos fuera de rangos terapéuticos es un problema hospitalario, pues pocas veces se tienen en cuenta parámetros antropométricos del paciente, determinantes en las concentraciones del medicamento. Objetivo: aplicar un modelo matemático basado en parámetros del paciente, para determinar las posibles concentraciones plasmáticas de cefalotina y compárarlas con las concentraciones mínimas inhibitorias de los microrganismos aislados. Métodos: se seleccionó un grupo de pacientes del sexo masculino entre 18 y 50 años de edad con tratamiento profiláctico posquirúrgico con cefalotina. Se recopiló la información: dosis de cefalotina, peso, talla, edad, hematócrito. Se calcularon volumen extracelular, plasmático y sanguíneo según el modelo informado por Hedin. Luego se calculó la concentración plasmática de cefalotina usando el modelo propuesto en el presente estudio y se comparó con la concentración mínima inhibitoria de los microorganismos aislados. Resultados: se analizaron 24 pacientes con promedio de edad 32,6 años ± 8, peso de 69 kg ± 7,51, talla de 168,87 cm ± 7,10. El 56,3 por ciento de los microorganismos presentó resistencia a concentraciones ³ 32 µg/mL. El agente más común fue Escherichia coli de 18 cepas aisladas. La comparación del volumen de distribución y la concentración plasmática de cefalotina calculada con el modelo informado por Hedin y el desarrollado en presente trabajo, no presentó diferencia significativa después de aplicar la prueba t de Student, con p< 0,05. Conclusiones: al comparar las concentraciones teóricas de cefalotina para uso profiláctico posquirúrgico intrahospitalario, calculadas con el modelo planteado, se encontró que estas no permitieron superar la concentración mínima inhibitoria de los microorganismos aislados(AU)

Introduction: the use of drugs out of therapeutic ranges is a hospital problem since the anthropometric parameters of patients, which are determinants in the drug concentrations, are rarely taken into consideration. Objectives: to implement a mathematical model based on the patient's parameters in order to determine the possible plasma cephalotine concentrations and to compare them with the minimum inhibitory concentrations for isolated microorganisms. Methods: a group of male patients aged 18 to 50 years under postsurgical prophylactic treatment with cephalotine was selected. Data was collected on cephalotin dosage, weight, size, age and hematocrit. Extracellular, plasma and blood volumes were estimated by the Hedin's informed model. Additionally, the plasma cephalotin concentration was measured by using the model suggested in this study and then compared with the minimum inhibitory concentration for the isolated microorganisms. Results: twenty four patients aged 32.6 years ± 8, weighing 69 kg ± 7.51, with size of 168.87 cm ± 7.10 were analyzed. Resistance to concentrations equal to or higher than 32 µg/mL was observed in 56.3 percent of microorganisms. The most common agent was Escherichia coli in 18 isolated strains. The comparison of the distribution volume and of the plasma cephalotin concentration estimated with the Hedin's informed model and with the model devised in the present paper did not show significant differences according to Student's t test result, with p< 0.05. Conclusions: the comparison of the theoretical concentrations of cephalotine for in-hospital postsurgical prophylactic use estimated by the model yielded that these concentrations did not allow overcoming the minimum inhibitory concentration for the isolated microorganisms(AU)

Changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization at admission to ICU and the relation to outcome.

OBJECTIVE: To evaluate the changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization in the ICU and their relation to outcome. DESIGN: Prospective observational study. SETTING: ICU of a veterinary university medical center. ANIMALS: Thirty dogs with severe sepsis or septic shock caused by pyometra who underwent surgery and were admitted to the ICU. MEASUREMENTS AND MAIN RESULTS: Severe sepsis was defined as the presence of sepsis and sepsis-induced dysfunction of one or more organs. Septic shock was defined as the presence of severe sepsis plus hypotension not reversed with fluid resuscitation. After the presumptive diagnosis of sepsis secondary to pyometra, blood samples were collected and clinical findings were recorded. Volume resuscitation with 0.9% saline solution and antimicrobial therapy were initiated. Following abdominal ultrasonography and confirmation of increased uterine volume, dogs underwent corrective surgery. After surgery, the animals were admitted to the ICU, where resuscitation was guided by the clinical parameters, central venous oxygen saturation (ScvO(2)), lactate, and base deficit. Between survivors and nonsurvivors it was observed that the ScvO(2), lactate, and base deficit on ICU admission were each related independently to death (P = 0.001, P = 0.030, and P < 0.001, respectively). ScvO(2) and base deficit were found to be the best discriminators between survivors and nonsurvivors as assessed via receiver operator characteristic curve analysis. CONCLUSION: Our study suggests that ScvO(2) and base deficit are useful in predicting the prognosis of dogs with severe sepsis and septic shock; animals with a higher ScvO(2) and lower base deficit at admission to the ICU have a lower probability of death.

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%).

Pyodermatitis-pyostomatitis vegetans: case report and review of medical literature.

Pyodermatitis-pyostomatitis vegetans is a rare inflammatory dermatosis of unknown etiology, with a typical mucocutaneous involvement. We report the case of a woman with pustular and vesicular lesions in the axillae, evolving with vegetating plaques and pustules with annular grouping. The disease progressed with vulvar and inguinal involvement as well as involvement of the oral, nasal and ocular mucous membranes. She started the treatment with prednisone (40 mg/day), with remission of the lesions after one month of use of such medication. Association with inflammatory bowel disease occurs in 70% of the cases. Immunofluorescence, which is typically negative, helps to characterize the disease. A rapid response to systemic steroids is expected.