Clinical implications of cefazolin inoculum effect and ß-lactamase type on methicillin-susceptible Staphylococcus aureus bacteremia.

BACKGROUND: Cefazolin is a common antibiotic for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Type A or C ß-lactamase-producing MSSA frequently shows the cefazolin inoculum effect (CIE). However, the clinical implication of the CIE for MSSA bacteremia is obscure. METHODS: MSSA bacteremic patients treated with cefazolin were included in a retrospective cohort study. The blaZ gene of the isolates was sequenced to identify the type of ß-lactamase. The patients whose isolates showed a ≥4-fold increase in cefazolin, the minimal inhibitory concentration (MIC) at the high inoculum (∼5×10(7) CFU/ml), were assigned to the CIE-positive group and the remainder to the CIE-negative group. Treatment failure was assessed at 12 weeks after cefazolin was initiated. RESULTS: A total of 113 MSSA bacteremic patients were included. Among the 113 isolates, 57.5% showed the CIE and 77.9% carried the blaZ gene; type A ß-lactamase was 15.0% and type C was 40.7%. Persistent bacteremia was more common in the CIE-positive group (9% vs. 0%, p=0.04). Treatment failure rates were higher in the CIE-positive group with high bacterial burden infection, but the difference was not significant (48% vs. 25%, p=0.13). There was no significant difference of failure between groups with high-inoculum MIC ≥16 and ≤1 µg/ml (13% vs. 5%, p=0.31). In the multivariable analysis, underlying cardiovascular diseases, pneumonia, osteoarticular infections, and endocarditis were significant risk factors for treatment failure and the CIE was not significantly associated with treatment failure. CONCLUSION: The CIE might be associated with persistent bacteremia if cefazolin is used for MSSA bacteremia with a high burden of infections. However, the sites of infections are more important factors for the clinical outcome than the CIE.

Metabolic response to Klebsiella pneumoniae infection in an experimental rat model.

Bacteremia, the presence of viable bacteria in the blood stream, is often associated with several clinical conditions. Bacteremia can lead to multiple organ failure if managed incorrectly, which makes providing suitable nutritional support vital for reducing bacteremia-associated mortality. In order to provide such information, we investigated the metabolic consequences of a Klebsiella pneumoniae (K. pneumoniae) infection in vivo by employing a combination of (1)H nuclear magnetic resonance spectroscopy and multivariate data analysis. K. pneumoniae was intravenously infused in rats; urine and plasma samples were collected at different time intervals. We found that K. pneumoniae-induced bacteremia stimulated glycolysis and the tricarboxylic acid cycle and also promoted oxidation of fatty acids and creatine phosphate to facilitate the energy-demanding host response. In addition, K. pneumoniae bacteremia also induced anti-endotoxin, anti-inflammatory and anti-oxidization responses in the host. Furthermore, bacteremia could cause a disturbance in the gut microbiotal functions as suggested by alterations in a range of amines and bacteria-host co-metabolites. Our results suggest that supplementation with glucose and a high-fat and choline-rich diet could ameliorate the burdens associated with bacteremia. Our research provides underlying pathological processes of bacteremia and a better understanding of the clinical and biochemical manifestations of bacteremia.

Beneficial effects of supplementation with branched-chain amino acids on postoperative bacteremia in living donor liver transplant recipients.

The aim of this study was to investigate the effects of preoperative oral supplementation with branched-chain amino acids (BCAAs) on postoperative bacteremia after living donor liver transplantation (LDLT) for chronic liver failure. Two hundred thirty-six patients who underwent adult-to-adult LDLT were evaluated in this retrospective study. The patients were divided into 2 groups: those who received oral supplementation with BCAAs before transplantation (the BCAA group; n = 129) and those who did not (the non-BCAA group; n = 107). Before the LDLT indication was determined, BCAA supplementation was prescribed by a hepatologist to preserve hepatic reserves. The clinical characteristics and the incidence of bacteremia were compared between the 2 groups. As for clinical characteristics, the Child-Pugh scores (P = 0.0003) and the Model for End-Stage Liver Disease scores (P = 0.0008) were significantly higher in the BCAA group versus the non-BCAA group. The incidence of bacteremia for Child-Pugh class C patients was significantly lower in the BCAA group (6/90 or 6.7%) versus the non-BCAA group (11/50 or 22.0%, P = 0.0132). In a multivariate analysis, non-BCAA supplementation was an independent risk factor for bacteremia. In conclusion, preoperative BCAA supplementation might reduce the incidence of bacteremia after LDLT. Nevertheless, this is a preliminary report, and further studies, such as randomized, prospective studies, are necessary to clarify the beneficial effects of BCAA supplementation on postoperative bacteremia after liver transplantation.

Comparative efficacies of amoxicillin, clindamycin, and moxifloxacin in prevention of bacteremia following dental extractions.

We evaluated the efficacies of oral prophylactic treatment with amoxicillin (AMX), clindamycin (CLI), and moxifloxacin (MXF) in the prevention of bacteremia following dental extractions (BDE). Two hundred twenty-one adults who required dental extractions under general anesthesia were randomly assigned to a control group, an AMX group, a CLI group, and an MXF group (the individuals in the drug treatment groups received 2 g, 600 mg, and 400 mg, respectively, 1 to 2 h before anesthesia induction). Venous blood samples were collected from each patient at the baseline and 30 s, 15 min, and 1 h after the dental extractions. The samples were inoculated into BACTEC Plus aerobic and anaerobic blood culture bottles and were processed in a BACTEC 9240 instrument. Subculture and the further identification of the isolated bacteria were performed by conventional microbiological techniques. The prevalences of BDE in the control group, AMX group, CLI group, and MXF group were 96, 46, 85, and 57%, respectively, at 30 s; 64, 11, 70, and 24%, respectively, at 15 min; and 20, 4, 22, and 7%, respectively, at 1 h. Streptococcus spp. were the most frequently identified bacteria in all groups (44 to 68%), with the lowest percentage being detected in the AMX group (44%). AMX and MXF prophylaxis showed high efficacies in reducing the prevalence and duration of BDE, but CLI prophylaxis was noneffective. As a consequence, MXF prophylaxis is a promising antibiotic alternative for the prevention of BDE when beta-lactams are not indicated.

Pharmacokinetics of once-daily amikacin in healthy foals and therapeutic drug monitoring in hospitalized equine neonates.

The objectives of this study were to investigate the pharmacokinetics of once-daily amikacin in healthy neonates, to determine amikacin concentrations in hospitalized foals, and to determine the minimum inhibitory concentrations (MICs) of amikacin against gram-negative isolates from blood cultures in septic foals. Median half-life, clearance, and volume of distribution of amikacin in healthy 2- to 3-day-old foals after administration of an intravenous bolus of amikacin (25 mg/kg) were 5.07 hours (4.86-5.45 hours), 1.82 mL/min/kg (1.35-1.97 mL/min/kg), and 0.785 L/kg (0.638-0.862 L/kg), respectively. Statistically significant (P <.05) decreases in area under the curve (14% decrease), mean residence time (19% decrease), and C24h plasma amikacin concentrations (29% decrease) occurred between days 2-3 and 10-11. Plasma amikacin concentrations in healthy foals at 0.5 hours (C0.5h) were significantly higher (P = .02) than those of hospitalized foals. Sepsis, prematurity, and hypoxemia did not alter amikacin concentrations. The MIC at which 90% of all gram-negative isolates from equine neonatal blood cultures were inhibited by amikacin was 4 microg/mL, suggesting that amikacin C0.5h of 40 microg/mL should be targeted to achieve a maximum serum concentration to MIC ratio of 10:1. The proportion of foals with C0.5h 40 microg/mL was significantly higher (P < .0001) in hospitalized foals receiving a dose of amikacin at 25 mg/kg (22/24 or 92%) than in foals receiving a dose at 21 mg/kg (9/25 or 36%), whereas no difference was found in the proportion of foals with C24h concentrations > or = 3 microg/mL between the 2 groups. An initial dose at 25 mg/kg is recommended for once-daily amikacin in equine neonates.

Acute effects of vitamin A on the kinetics of endotoxin in conscious rabbits.

BACKGROUND: Vitamin A reduces the pathophysiological effects of endotoxin in animals, but the mechanism and the lowest effective dose are not clear. METHODS: An intravenous bolus of endotoxin 20 microg. kg(-1) was given to 30 rabbits. In 10 of them, 1000 IE. kg(-1) retinyl palmitate was injected intravenously 1 h before the endotoxin and in another 10 rabbits 1 h after the endotoxin. A one-compartment open model was fitted to the time-concentration profile of endotoxin in plasma. RESULTS: The half-life of endotoxin was half as long when vitamin A was given for prophylaxis (median 35 min) and for treatment (33 min) than in the controls (67 min; p < 0.004). The plasma concentrations of immunoglobulin G and M endotoxin-core antibodies, the leucocyte count and the acid-base balance did not differ between the groups during the experiment, but the pyrogenic reaction was more pronounced in the controls. CONCLUSION: A fairly low dose of vitamin A reduced the half-life of endotoxin.

Comparative efficacies of levofloxacin and ciprofloxacin against Streptococcus pneumoniae in a mouse model of experimental septicaemia.

The in vivo efficacies of levofloxacin and ciprofloxacin were compared against three clinical isolates of Streptococcus pneumoniae, using a mouse protection model. Two strains (SP 22 and SP 28) were penicillin-sensitive while one strain (SP 46) was penicillin-resistant. Each strain had identical susceptibility to both drugs. Using mice with renal impairment induced by uranyl nitrate injection, the elimination half-life of each antibiotic was prolonged to approximate human pharmacokinetic profiles of the drugs. The dosing regimen of each drug that yielded serum levels in mice which mimic human therapeutic concentrations of the drugs, were designed. One hour after intraperitoneal inoculation with minimum lethal dose of each strain, either levofloxacin at a dosing regimen of 10.6 mg/kg every 8 h or ciprofloxacin at 9.5 mg/kg every 8 h was subcutaneously administered for a total of six or 15 doses. In treatment, monitored daily for 5-8 days, levofloxacin resulted in higher survival compared with ciprofloxacin for the three strains. For example, percent survival following levofloxacin treatment recorded at day 4 postinfection with SP 22, SP 28 and SP 46 were 41, 90 and 30%, respectively, while the corresponding values after ciprofloxacin treatment were 27, 75 and 16%, respectively. However, statistical analysis did not reveal a significant difference (p > 0.05). The lack of significant difference observed in the efficacies of both drugs reflected the comparability of their 24-h AUC/MIC ratios. It is suggested that, with some strains of S. pneumoniae, the efficacy of levofloxacin may be equivalent to that of ciprofloxacin in the treatment of systemic pneumococcal infections caused by susceptible strains of the organism.