Pharmacokinetic/pharmacodynamic evaluation of the antimicrobial therapy of pneumococcal invasive disease in adults in post-PCV13 vaccine period in Madrid, Spain.

The objective of our study was to evaluate by pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the antimicrobials used for the treatment of invasive pneumococcal disease (IPD) in adults, including meningitis, are adequate considering the susceptibility profile of S. pneumoniae in Spain after the implantation of PVC13 vaccine. Pharmacokinetic parameters of benzylpenicillin and cefotaxime were obtained from the literature, and susceptibility data of invasive S. pneumoniae strains recovered in 2017 (post-PCV13 vaccination period) were provided by the Public Health Regional Laboratory of Madrid. We have also studied levofloxacin because it is used to treat pneumococcal pneumonia previously to be diagnosed as bacteremic pneumonia. Monte Carlo simulation was used to estimate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). All doses of benzylpenicillin except 2 mU q6h provide a high probability of treatment success for MIC values ≤ 1 mg/L; 4 mU q4h is even useful for MIC values up to 4 mg/L. This high dose, used for the treatment of meningitis, also provides high probability of treatment success for MIC ≤ 0.5 mg/L. At the susceptibility EUCAST breakpoint (≤ 0.5 mg/L), cefotaxime provides a high rate of PD target achievement, even at the lowest dose (1 g q8h). For meningitis, 2 g q6h ensures probabilities of target attainment ≥90% for MIC up to 1 mg/L. Our study confirms that after the implementation of PCV13 vaccine, the treatment with benzylpenicillin and cefotaxime provides high probability of the therapy success of IPD, including meningitis.

Continuous versus intermittent infusion of cefotaxime in critically ill patients: a randomized controlled trial comparing plasma concentrations.

BACKGROUND: In critical care patients, reaching optimal ß-lactam concentrations poses challenges, as infections are caused more often by microorganisms associated with higher MICs, and critically ill patients typically have an unpredictable pharmacokinetic/pharmacodynamic profile. Conventional intermittent dosing frequently yields inadequate drug concentrations, while continuous dosing might result in better target attainment. Few studies address cefotaxime concentrations in this population. OBJECTIVES: To assess total and unbound serum levels of cefotaxime and an active metabolite, desacetylcefotaxime, in critically ill patients treated with either continuously or intermittently dosed cefotaxime. METHODS: Adult critical care patients with indication for treatment with cefotaxime were randomized to treatment with either intermittent dosing (1 g every 6 h) or continuous dosing (4 g/24 h, after a loading dose of 1 g). We defined a preset target of reaching and maintaining a total cefotaxime concentration of 4 mg/L from 1 h after start of treatment. CCMO trial registration number NL50809.042.14, Clinicaltrials.gov NCT02560207. RESULTS: Twenty-nine and 30 patients, respectively, were included in the continuous dosing group and the intermittent dosing group. A total of 642 samples were available for analysis. In the continuous dosing arm, 89.3% met our preset target, compared with 50% in the intermittent dosing arm. Patients not reaching this target had a significantly higher creatinine clearance on the day of admission. CONCLUSIONS: These results support the application of a continuous dosing strategy of ß-lactams in critical care patients and the practice of therapeutic drug monitoring in a subset of patients with higher renal clearance and need for prolonged treatment for further optimization, where using total cefotaxime concentrations should suffice.

Pediatric acute dacryocystitis due to Eikenella corrodens: A case report.

Eikenella corrodens is a facultatively anaerobic gram-negative rod bacterium in the oropharynx and respiratory tract. It is a member of HACEK (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, E. corrodens, and Kingella kingae) group commonly associated with endocarditis and craniofacial infections. It is usually susceptible to penicillin, second and third-generation cephalosporins, and carbapenem, but has variable susceptibility to first-generation cephalosporin. We herein provide a description of the first case of pediatric acute dacryocystitis caused by E. corrodens. The patient did not respond to oral cephalexin and required surgical drainage followed by intravenous cefotaxime. Also provided is a brief review of the current literature.

Meropenem versus Cefotaxime and Ampicillin as Empirical Antibiotic Treatment in Adult Bacterial Meningitis: a Quality Registry Study, 2008 to 2016.

Cefotaxime, alone or with ampicillin, is frequently used in empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less extensively investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM. The study was based on data from the Swedish quality register for ABM collected between January 2008 and December 2016. Propensity score matching was performed to adjust for baseline differences between the groups. Mortality within 30 days was the primary outcome. The treatment regimens of interest were administered to 623 patients; 328 were given cefotaxime plus ampicillin whereas 295 received meropenem. Using propensity score matching, the 30-day mortality rates were 3.2% in the cefotaxime plus ampicillin group and 3.6% in the meropenem group. For matched cases, the odds ratio (OR) for 30-day mortality for meropenem versus cefotaxime plus ampicillin was 1.15 (confidence interval [CI], 0.41 to 3.22; P = 0.79). The OR for 90-day mortality was 1.47 (CI, 0.62 to 3.52; P = 0.38) and for unfavorable outcome was 1.10 (CI, 0.75 to 1.63; P = 0.62). The findings of our study indicate that meropenem is an effective empirical treatment option for adults with community-acquired ABM. However, to spare carbapenems, guidelines should continue to recommend third-generation cephalosporins as an empirical treatment for the majority of patients with ABM.

Population Pharmacokinetics of Cefotaxime and Dosage Recommendations in Children with Sickle Cell Disease.

The pharmacokinetic profile of most drugs is dependent on the patient's covariates and may be influenced by the disease. Cefotaxime is frequently prescribed in pediatric patients with sickle cell disease (SCD), characterized by vaso-occlusive complications, chronic hemolytic anemia, and a defective immunological function predisposing the individual to severe infection. Data on the impact of the disease on the disposition of cefotaxime are missing. In the present study, our aims were to determine cefotaxime pharmacokinetics when prescribed to children with SCD for suspected or proven bacterial infection, identify significant covariates, and perform Monte Carlo simulations to optimize the drug dosage. Cefotaxime serum concentrations were measured in 78 pediatric SCD patients receiving cefotaxime intravenously at a daily dose of 200 mg/kg of body weight in three or four divided doses over 30 min. A total of 107 concentrations were available for pharmacokinetic analysis. A population pharmacokinetic model was developed with NONMEM software and used for Monte Carlo simulations. Cefotaxime concentrations ranged from 0.05 to 103.7 mg/liter. Cefotaxime pharmacokinetics were best described by a one-compartment model: the median estimated weight-normalized volume of distribution and clearance were 0.42 liter/kg (range, 0.2 to 1.1 liter/kg) and 0.38 liter/h/kg (range, 0.1 to 1.2 liter/h/kg). Cefotaxime clearance increased by 22% in patients with acute chest syndrome. Dosing optimization, performed using EUCAST MIC susceptibility breakpoints, showed that a dose of 100 mg/kg/6 h should be used, depending on the patient's characteristics and clinical presentation, in order to reach a value of the percentage of time that the drug concentration exceeded the MIC under steady-state pharmacokinetic conditions of 80% in 80% of the patients when targeting sensitive Gram-positive cocci and Gram-negative bacilli with MICs of 1 mg/liter or below.

Cephalosporin-resistant Escherichia coli isolated from farm workers and pigs in northern Vietnam.

OBJECTIVE: Antimicrobial-resistant bacteria may be transmitted between farm workers and livestock. This study aimed to determine and compare the prevalence and the genetic determinants of cefotaxime-resistant and ESBL-producing Escherichia coli in faecal isolates from workers and pigs at 100 farms in northern Vietnam. METHODS: Farmers were interviewed about antimicrobial usage in livestock. Escherichia coli isolated on MacConkey agar containing 2 mg/l of cefotaxime (CTX) were tested for susceptibility to different cephalosporins by disc diffusion and screened for occurrence of ESBL-encoding genes by PCR. RESULTS: Antimicrobial usage was widespread and included classes regarded of critical or high importance in human medicine. Dosages were 0.5-2 times higher than recommended, and antimicrobials were often administered right until slaughter. Prevalence of CTX-resistant E. coli was 86% in farm workers and 89% in pigs. In 76% of farms, CTX-resistant E. coli were shared by pigs and farm workers. ESBL-producing E. coli were detected from pigs and workers at 66 and 69 farms, respectively. The ESBL phenotype was mainly mediated by CTX-M and to a lesser extent by TEM. Occurrence of blaCTX-M was similar in E. coli from pigs (66.7%) and humans (68.5%). CONCLUSION: The high occurrence of ESBL-producing E. coli in pig farmers and pigs could present a risk for spillover of these bacteria from pig farms into the community. Genomic studies are needed to elucidate reservoirs and transmission routes of ESBL-producing E. coli at livestock farms.

Severe hemolysis after plasma transfusion in a neonate with necrotizing enterocolitis, Clostridium perfringens infection, and red blood cell T-polyagglutination.

BACKGROUND: Red blood cell (RBC) Thomsen-Friedenreich antigen exposure (T activation) in infants with necrotizing enterocolitis (NEC) has occasionally been associated with posttransfusional intravascular hemolysis thought to be due to anti-T antibodies in the donor plasma. STUDY DESIGN AND METHODS: We describe an infant with NEC and Clostridium perfringens infection complicated by severe hemolysis after plasma transfusion. After this case, infants with confirmed NEC were prospectively evaluated for T activation. We checked for hemolysis in patients with T activation receiving plasma-containing blood products. RESULTS: The infant had received 80 mL of fresh-frozen plasma (FFP). His RBCs displayed strong T activation, and agglutination was observed with four of six ABO-compatible FFP units. A direct antiglobulin test was negative. IgM-class anti-T antibodies were present in small amounts (titer of 8) in the transfused FFP. Anti-T antibodies from the blood donor were not hemolytic in vitro. In the prospective study, T activation was observed in three of 28 infants with NEC (11%). One infant presented moderate T activation and two infants presented very strong T activation but only moderate decreases in sialic acid expression on the RBC membrane. These three infants presented no signs of hemolysis after transfusion with unwashed blood products or FFP. CONCLUSION: Anti-T antibodies are unlikely to be the etiologic factor for the hemolytic reactions observed in infants with NEC and T activation. Massive RBC desialylation and the direct action of bacterial toxins are more probable causes. Strict avoidance of plasma-containing blood products does not seem justified in these infants.

Nanosized Liposomes Containing Bile Salt: A Vesicular Nanocarrier for Enhancing Oral Bioavailability of BCS Class III Drug.

PURPOSE: Liposomes have been studied as a colloidal carrier in drug delivery systems, especially for oral administration. However, their low structural integrity in the gut is still a major shortcoming. Membrane disruptive effects of physiological bile salts in the small intestine result in premature drug release prior to intestinal absorption. Thus, we analyzed the stabilizing effect of sodium deoxycholate when incorporated into nano-sized liposomes. METHOD: Cefotaxime-loaded liposomes were prepared with different sodium deoxycholate concentrations (3.75- 30 mM) by rotary film evaporation followed by nano-size reduction. The physical integrity of liposomes was evaluated by monitoring cefotaxime leakage, particle sizes in different simulated physiological media. The oral bioavailability and pharmacokinetics of cefotaxime was assessed in rats (n = 6 per group) after single dose of drug-encapsulated in liposomes containing bile salt, drug in conventional liposomes, and cefotaxime solution (oral and intravenous). RESULTS: Simulated gastric fluid with low pH showed less effect on the stability of liposomes in comparison to media containing physiological bile salts.  Liposomes containing 15 mM sodium deoxycholate were most stable in size and retained the majority of encapsulated cefotaxime even in fed state of simulated intestinal fluid being the most destructive media. Pharmacokinetics data showed an increase in Cmax and AUC0-inf in the following order: cefotaxime solution < conventional liposomes < liposomes made with bile salts. The total oral bioavailability of cefotaxime in liposomes containing bile salt was found to be 5-times higher compared to cefotaxime solution and twice as much as in conventional liposomes. CONCLUSION: Incorporation of bile salts, initially used as membrane permeation enhancer, also acted as a stabilizer against physiological bile salts. The nano-sized liposomes containing sodium deoxycholate were able to reduce the leakage of encapsulated cefotaxime in the gut due to the improved vesicle stability and to enhance the oral bioavailability of acid-labile drugs up to 5-fold. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Clinical practice audit concerning antimicrobial prophylaxis in paediatric neurosurgery: results from a German paediatric oncology unit.

BACKGROUND: Perioperative antimicrobial prophylaxis (PAP) has been identified as an important target for internal audits, concerning the judicious use of antibiotics. Paediatric oncology patients with brain tumours face an increased risk of surgical site infection (SSI) after neurosurgery and receive routine PAP in this setting. PATIENTS AND METHODS: All patients younger than 18 years admitted to the paediatric oncology centre (POC) with a neurosurgical intervention. Systematic audit of routine clinical data is divided in two groups: retrospective (Jan 01, 2012-March 31, 2014) and prospective (April 01, 2014-March 31, 2015) referring to an internal PAP guideline, invented in Jan. 2014). Surveillance of SSI up to 30 days after the operation with standard criteria (Centres for Disease Control and Prevention, USA). RESULTS: In total, 53 neurosurgical operations were analysed in 33 paediatric oncology patients. Twelve patients received more than one operation. The detailed analysis of PAP revealed prophylactic cefuroxim doses about 30 mg/kg instead of 50 mg/kg and no repeated dosing in operations lasting longer than 4 h. In addition, Cefotaxim, which is not indicated as PAP in neurosurgery, was used instead of Cefuroxim (or Ampicillin-Sulbactam) in 23 % of all cases in the retrospective and 18 % of all cases in the prospective audit. PAP for more than 3 doses (>24 h) was administered in 66 % in the retrospective group and in 60 % in the prospective group (p = n.s.). In both groups, no SSI was detected. DISCUSSION: This first comprehensive audit of PAP in paediatric oncology patients undergoing neurosurgery outlines significant opportunities to improve clinical practice in terms of correct dosing, the correct choice of the antibiotic, a correct timing schedule and a shorter duration of PAP. In addition, our results illustrate in detail the challenges in clinical practice when an evidence-based approach to improve a standard workflow has to be implemented.

Nonchemotherapy drug-induced agranulocytosis in children detected by a prospective pharmacovigilance program.

OBJECTIVES: A prospective evaluation of nonchemotherapy drug-induced agranulocytosis (DIA) cases, which are infrequent in the pediatric population. We characterize agranulocytosis cases and assess lab test differences between drug- and nondrug-induced agranulocytosis. METHODS: Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital we detected pediatric agranulocytosis cases from July 2007 to December 2010. This program estimates the incidence, drug causality, clinical features, outcomes of DIA pediatric cases, and assesses laboratory differences with respect to non-DIA. RESULTS: We detected 662 agranulocytosis in 308 pediatric patients, of which 14 were caused by nonchemotherapy drugs. The incidence rate of DIA for 10,000 pediatric patients was 3.92 (Poisson 95% confidence interval 1.09-8.77); 78.6% of DIA cases occurred in patients younger than 3 years. The final outcome was recovery without sequela in all cases. The pharmacologic group most frequently implicated was antimicrobial drugs (11 drugs), 7 of which were beta-lactams. The drugs most frequently suspected were cefotaxime and vancomycin (3 cases each). We found 3 drugs (cloperastine, codeine, and enoxaparin) not previously described to induce DIA. Automatic linear modeling (n = 56, R2 = 45.2%) showed a significant inverse association with platelets (R2 = 17.5%), hemoglobin, and alanine transaminase, and a direct association with red cell distribution (R2 = 16.2%). A generalized linear model (Type III, n = 1188; DIA, n = 86; likelihood ratio chi-squared = 156.16) retained eosinophils (p <.001), platelets (p <.001), total serum proteins (p <.001), and hemoglobin (p =.039). CONCLUSIONS: We found a higher incidence of DIA in children than previously described. Our findings also suggest an immune-mediated destruction or myeloid toxicity, possibly facilitated by an increase in drug exposure.

Occurrence of conjugative IncF-type plasmids harboring the blaCTX-M-15 gene in Enterobacteriaceae isolates from newborns in Tunisia.

BACKGROUND: CTX-M-15 is the dominant type of extended-spectrum ß-lactamase in clinical isolates. This enzyme constitutes the most widespread enzymes in Tunisia. In this study, we were interested to understand the causes of the evolutionary success of CTX-M-15 in a Tunisian university hospital. METHODS: A total of of 72 cefotaxime-resistant Enterobacteriaceae were isolated from newborn patients at the hospital Taher sfar Mahdia in Tunisia and characterized their genetic support by means of molecular techniques. RESULTS: Isolates were clustered into various clonal groups, although most isolates belonged to sequence types ST39 (Klebsiella pneumoniae) and ST131 (Escherichia coli). F replicons (FIA, FIB, and FII) were the most frequently detected replicon types in our collection (91.66%). CONCLUSION: This is the first report of QnrB- and CTX-M-15-encoding large IncF-type conjugative plasmids in Tunisia.

Efficacy and safety of pharmacological treatments for acute Lyme neuroborreliosis - a systematic review.

BACKGROUND AND PURPOSE: Our aim was to evaluate the available evidence for pharmacological treatment of acute Lyme neuroborreliosis as a basis for evidence-based clinical recommendations in a systematic review. METHODS: A systematic literature search of Medline, EMBASE, the Cochrane Library and three trial registries was performed. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools. The primary outcome was 'residual neurological symptoms' whilst the secondary outcomes were disability, quality of life, pain, fatigue, depression, cognition, sleep, adverse events and cerebrospinal fluid pleocytosis. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: After screening 5779 records, eight RCTs and eight NRS were included. Risk of bias was generally high. No statistically significant difference was found between doxycycline and beta-lactam antibiotics in a meta-analysis regarding residual neurological symptoms at 4-12 months [risk ratio (RR) 1.27, 95% confidence interval (CI) 0.98-1.63, P = 0.07] or adverse events (RR 0.82, 95% CI 0.54-1.25, P = 0.35). Significantly fewer neurological symptoms for cefotaxime compared with penicillin were found (RR 1.81, 95% CI 1.10-2.97, P = 0.02). Adverse events were significantly fewer for penicillin (RR 0.56, 95% CI 0.38-0.84, P = 0.005). CONCLUSIONS: Evidence regarding pharmacological treatment of acute Lyme neuroborreliosis is scarce and therefore insufficient to recommend preference of beta-lactam antibiotics over doxycycline or vice versa. However, due to considerable imprecision, relevant differences between treatments cannot be excluded. No evidence suggesting benefits of extended antibiotic treatments could be identified. Further well-designed trials are needed. Individual treatment decisions should address patients' preferences and individual conditions like prior allergic reactions.

Synergistic effects and antibiofilm properties of chimeric peptides against multidrug-resistant Acinetobacter baumannii strains.

The increasing prevalence of drug-resistant pathogens highlights the need to identify novel antibiotics. Here we investigated the efficacies of four new antimicrobial peptides (AMPs) for potential drug development. The antibacterial activities, synergistic effects, and antibiofilm properties of the four chimeric AMPs were tested against Acinetobacter baumannii, an emerging Gram-negative, nosocomial, drug-resistant pathogen. Nineteen A. baumannii strains resistant to ampicillin, cefotaxime, ciprofloxacin, tobramycin, and erythromycin were isolated at a hospital from patients with cholelithiasis. All four peptides exhibited significant antibacterial effects (MIC=3.12 to 12.5 µM) against all 19 strains, whereas five commercial antibiotics showed little or no activity against the same pathogens. An exception was polymyxin, which was effective against all of the strains tested. Each of the peptides showed synergy against one or more strains when administered in combination with cefotaxime, ciprofloxacin, or erythromycin. The peptides also exhibited an ability to prevent biofilm formation, which was not seen with cefotaxime, ciprofloxacin, or erythromycin, though polymyxin also inhibited biofilm formation. Indeed, when administered in combination with ciprofloxacin, the AMP HPMA exerted a potent synergistic effect against A. baumannii biofilm formation. Collectively, our findings indicate that the AMPs tested have no cytotoxicity but possess potent antibacterial and antibiofilm activities and may act synergistically with commercial antibiotics.

Verified clinical failure with cefotaxime 1g for treatment of gonorrhoea in the Netherlands: a case report.

We describe the first case of treatment failure of gonorrhoea with a third generation cephalosporin, cefotaxime 1g intramuscularly, in the Netherlands. The case was from a high-frequency transmitting population (men having sex with men) and was caused by the internationally spreading multidrug-resistant gonococcal NG-MAST ST1407 clone. The patient was clinically cured after treatment with ceftriaxone 500 mg intramuscularly and this is the only third generation cephalosporin that should be used for first-line empiric treatment of gonorrhoea. Increased awareness of failures with third generation cephalosporins, enhanced monitoring and appropriate verification of treatment failures including more frequent test-of-cures, and strict adherence to regularly updated treatment guidelines are essential globally.

Does selective digestive decontamination prevent ventilator-associated pneumonia in trauma patients?

The incidence of ventilator-associated pneumonia (VAP) is particularly high in patients with trauma. The efficacy and safety of selective digestive decontamination (SDD) was not studied extensively. We aimed in our randomized double-blind, placebo-controlled study to evaluate whether SDD prevents VAP onset in multiple trauma patients. All adult patients admitted in our intensive care unit for multiple trauma with a predicted duration of mechanical ventilation (MV) over 48 hours were included. We included 44 patients who were divided into 4 groups: group A receiving subglottic and gastric treatment suspension (polymyxin E 100 mg, vancomycin 1 g, and amphotericin B 500 mg), group B receiving placebo, group C receiving subglottic placebo and gastric treatment suspension, and group D receiving subglottic treatment suspension and gastric placebo. The suspension was given 4 times a day during 7 consecutive days. To this topical treatment, we associated an intravenous administration of cefotaxime (1 g 3 times a day during 4 consecutive days). The incidence of VAP in the 4 groups was, respectively, 45.5%, 46.2%, 22.2%, and 27.3% (P=0.236). In multivariate analysis, none of the 3 tested regimens was identified as a protective factor against VAP. However, prolonged duration of MV was the only independent factor predicting VAP onset (odds ratio=1.1; 95% confidence interval [1.1-1.4]; P=0.049).

Comparison of two empiric antibiotic regimen in late onset neonatal sepsis--a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of two antibiotic regimens among neonates with late onset sepsis (LOS). METHODS: This randomized controlled trial conducted in a tertiary care teaching hospital, South India, included 90 babies with LOS. Detailed history, examination and appropriate investigations were done for all the babies. Cloxacillin + Amikacin were administered to 40 and Cefotaxime + Gentamicin to 50 babies. Outcomes including mortality, complications and treatment failure were evaluated. Chi-square test was used for categorical variables and Student's unpaired t-test for continuous variables. RESULTS: LOS had a male preponderance, and median time of onset was 13 days. Mortality was more among low birth weight babies irrespective of the antibiotics. Predominant bacteria isolated were coagulase-negative staphylococci (26.67%), Escherichia coli (13.33%) and Streptococcus pneumoniae (13.33%). Complications, mortality and cost were similar in both regimens. CONCLUSION: There was no significant difference between the two antibiotic regimens with regard to outcome of LOS.

Comparison of continuous infusion with intermittent bolus administration of cefotaxime on blood and cavity fluid drug concentrations in neonatal foals.

Healthy neonatal foals were treated with cefotaxime by bolus (40 mg/kg i.v. q6h for 12 doses; n=10) or by infusion (loading dose of 40 mg/kg i.v. followed by continuous infusion of a total daily dose of 160 mg/kg per 24 h for 3 days; n=5). Population pharmacokinetics was determined, and concentrations in cavity fluids were measured at steady state (72 h). Highest measured serum drug concentration in the bolus group was 88.09 µg/mL and minimum drug concentration (C(min)) was 0.78 µg/mL at 6-h postadministration (immediately before each next dose), whereas infusion resulted in a steady-state concentration of 16.10 µg/mL in the infusion group. Mean cefotaxime concentration in joint fluid at 72 h was higher (P=0.051) in the infusion group (5.02 µg/mL) compared to the bolus group (0.78 µg/mL). Drug concentration in CSF at 72 h was not different between groups (P=0.243) and was substantially lower than serum concentrations in either group. Insufficient data on pulmonary epithelial lining fluid were available to compare the methods of administration for cefotaxime in this cavity fluid. Results support continuous drug infusion over bolus dosing in the treatment for neonatal foal septicemia to optimize time that cefotaxime concentration exceeds the minimum inhibitory concentration of common equine pathogens.

Broad-spectrum ß-lactam antibiotics for treating experimental peritonitis in mice due to Klebsiella pneumoniae producing the carbapenemase OXA-48.

A lethal peritonitis model was induced in mice with a Klebsiella pneumoniae isolate producing the carbapenemase OXA-48. Administration of a single dose (up to 100 mg/kg) of the antibiotic piperacillin-tazobactam, imipenem-cilastatin, ertapenem, or cefotaxime had little or no impact on lethality. Ceftazidime had the highest efficacy in vivo, which mirrored its in vitro activity; this was not the case for carbapenems. Therefore, ceftazidime may be recommended for the treatment of infections due to OXA-48 producers if they do not coproduce an extended-spectrum ß-lactamase or a plasmid-mediated AmpC cephalosporinase.

Selective decontamination of the oral and digestive tract in surgical versus non-surgical patients in intensive care in a cluster-randomized trial.

BACKGROUND: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) are effective in improving survival in patients under intensive care. In this study possible differential effects in surgical and non-surgical patients were investigated. METHODS: This was a post hoc subgroup analysis of data from a cluster-randomized multicentre trial comparing three groups (SDD, SOD or standard care) to quantify effects among surgical and non-surgical patients. The primary study outcome was 28-day mortality rate. Duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital length of stay, and bacteraemia rates were secondary outcomes. RESULTS: The subgroup analyses included a total of 2762 surgical and 3165 non-surgical patients. Compared with standard care, adjusted odds ratios (ORs) for mortality were comparable in SDD-treated surgical and non-surgical patients: 0·86 (95 per cent confidence interval 0·69 to 1·09; P = 0·220) and 0·85 (0·70 to 1·03; P = 0·095) respectively. However, duration of mechanical ventilation, ICU stay and hospital stay were significantly reduced in surgical patients who had SDD. SOD did not reduce mortality compared with standard treatment in surgical patients (adjusted OR 0·97, 0·77 to 1·22; P = 0·801); in non-surgical patients it reduced mortality (adjusted OR 0·77, 0·63 to 0·94; P = 0·009) by 16·6 per cent, representing an absolute mortality reduction of 5·5 per cent with number needed to treat of 18. CONCLUSION: Subgroup analysis found similar effects of SDD in reducing mortality in surgical and non-surgical ICU patients, whereas SOD reduced mortality only in non-surgical patients. The hypothesis-generating findings mandate investigation into mechanisms between different ICU populations.