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Background and Aims: Ampicillin is 1 of the most commonly used antibiotics for treatment of early onset sepsis, but its pharmacokinetics (PK) is poorly characterized. We aimed to define the dose of ampicillin for late preterm and term neonates by evaluating its PK in serum, cerebrospinal (CSF), and epithelial lining fluid., Methods: A prospective study included neonates receiving ampicillin for suspected or proven early onset sepsis and pneumonia. PK samples were collected at steady state, at predose and 5 minutes, 1 hour, 3 hours, 8 hours, and 12 hours after ampicillin 3-minute infusion. Ampicillin concentrations were measured by ultra-high-performance liquid chromatography. Noncompartmental anaysis (NCA) and population pharmacokinetic (pop-PK) modeling were performed and probability of therapeutic target attainment was simulated., Results: In 14 neonates (GA of 32-42 wks; mean BW 2873 g), PK parameters (mean ± SD) in NCA were the following: half-life 7.21 ± 7.97 hours; volume of distribution (Vd) 1.07 ± 0.51 L; clearance (CL) 0.20 ± 0.13 L/h; 24-hour area under the concentration-time curve 348.92 ± 114.86 mg*h/L. In pop-PK analysis, a 2-compartmental model described the data most adequately with the final parameter estimates of CL 15.15 (CV 40.47%) L/h/70kg; central Vd 24.87 (CV 37.91%) L/70kg; intercompartmental CL 0.39 (CV 868.56) L/h and peripheral Vd 1.039 (CV 69.32%) L. Peutic target attainment simulations demonstrated that a dosage of 50 mg/kg q 12 hours attained 100% fT > MIC 0.25 mg/L, group B streptococcal breakpoint., Conclusions: We recommend ampicillin dosage 50 mg/kg q 12 hours for neonates with gestational age ≥32 weeks during the first week of life., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study was to compare the in vitro activity of ampicillin and moxifloxacin against six isolates selected from 154 invasive clinical isolates of Listeria monocytogenes and evaluate their intra- and extracellular activities with achievable central nervous system concentrations obtained using Monte Carlo simulations with conventional and unconventional dosages., Methodology: The MICs and minimal bactericidal concentrations (MBCs) of ampicillin and moxifloxacin were determined by using the broth microdilution method. The intra- and extracellular activities were compared using time-kill curves and inhibition of intracellular growth assays., Results: The MICs50/90 of ampicillin were 0.125/0.5 mg l-1 and the MBC50/90 was ≥16 mg l-1, while the moxifloxacin MICs50/90 were 0.25/0.5 mg l-1 and the MBC50/90 was 0.5 mg l-1. Ampicillin did not show any extracellular bactericidal activity at 24 h, although bactericidal activity was detected at 48 h. For moxifloxacin, the bactericidal effect was evident after 6 h of incubation. Both antibiotics achieved significant reductions in intracellular inoculum after 1-24 h of incubation; however, moxifloxacin becomes bactericidal more rapidly, producing a much greater reduction in the inoculum in the first hour than ampicillin. There were no differences among the MIC and MBC values of moxifloxacin and ampicillin among the strains belonging to different serotypes and/or epidemic clones. This fact was also found in the intra- and extracellular studies., Conclusion: The results of this study demonstrated the faster bactericidal activity of moxifloxacin at achievable central nervous system concentrations against intra- and extracellular forms of L. monocytogenes in comparison with ampicillin.

Chronic ethanol consumption is known to downregulate expression of the major glutamate transporter 1 (GLT-1), which increases extracellular glutamate concentrations in subregions of the mesocorticolimbic reward pathway. While β-lactam antibiotics were initially identified as potent upregulators of GLT-1 expression, only ceftriaxone has been extensively studied in various drug addiction models. Therefore, in this study, adult male alcohol-preferring (P) rats exposed chronically to ethanol were treated with other β-lactam antibiotics, ampicillin, cefazolin or cefoperazone (100mg/kg) once daily for five consecutive days to assess their effects on ethanol consumption. The results demonstrated that each compound significantly reduced ethanol intake compared to the saline-treated control group. Importantly, each compound significantly upregulated both GLT-1 and pAKT expressions in the nucleus accumbens and prefrontal cortex compared to saline-treated control group. In addition, only cefoperazone significantly inhibited hepatic aldehyde dehydrogenase-2 enzyme activity. Moreover, these β-lactams exerted only a transient effect on sucrose drinking, suggesting specificity for chronically inhibiting ethanol reward in adult male P rats. Cerebrospinal fluid concentrations of ampicillin, cefazolin or cefoperazone have been confirmed using high-performance liquid chromatography. These findings demonstrate that multiple β-lactam antibiotics demonstrate efficacy in reducing alcohol consumption and appear to be potential therapeutic compounds for treating alcohol abuse and/or dependence. In addition, these results suggest that pAKT may be an important player in this effect, possibly through increased transcription of GLT-1., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

The susceptibilities of 171 bacteria which caused meningitis in 200 children were tested for their susceptibility as minimal inhibitory concentrations (MICs) for the antibiotics used in therapy. These antibiotics were chloramphenicol, ampicillin, cefotaxime and ceftriaxone. The MICs were compared to the minimal concentrations of the drugs seen in the cerebrospinal fluid (CSF) samples. The minimal bacteriostatic capacity (lowest concentration in CSF/MIC) of both cephalosporins was superior to that of chloramphenicol and ampicillin. The correlation of the finding with the speed of liquor sterilization in the treatment groups is discussed.

We examined the influence of several pharmacokinetic parameters on cure rates in rabbits with experimental pneumococcal meningitis. When the duration of treatment was kept constant, cure rates improved as the individual dose of ampicillin was increased. On the other hand, when four doses of ampicillin at 60 mg/kg of body weight, producing peak concentrations in cerebrospinal fluid (CSF) of approximately 40 times the MBC, were administered at intervals of 24 instead of 4 h and the duration of therapy was thus prolonged from 12 to 72 h, cure rates also increased (85 versus 25%; P less than 0.01). These high cure rates were achieved even though bacterial titers in CSF 24 h after the first dose had reached levels similar to those present at the beginning of therapy. Cure in these animals was explained by the fact that the second ampicillin dose reduced bacterial titers in CSF significantly more than did the first dose (5.2 versus 2.5 log10 CFU/ml; P less than 0.02). The clinical relevance of these observations remains to be determined.

The concentration of antibiotic in cerebrospinal fluid was measured during treatment of seven children with infected ventricular shunts. Antibiotics were administered via the ventricular shunt or through an external ventricular drain. 53 CSF samples were obtained 7-19 h after antibiotic administration. Wide variation in cerebrospinal fluid antibiotic concentration occurred from patient to patient following either route of administration. For optimal management of shunt infections, we recommend periodic assessment of antibiotic concentration or activity in ventricular fluid and determination of the minimum inhibitory concentration of antibiotic required for each pathogen.

The penetration of antibiotics into the cerebrospinal fluid (CSF) is governed by several factors, including lipid solubility, degree of ionization, pH gradient, serum protein binding, molecular weight and structure and, above all, degree of meningeal inflammation. The distribution within, and elimination from the subarachnoid spaces depend upon the physiology of the CSF and the route of administration of the drug. CSF penetration studies carried out in patients or volunteers with various groups of antibiotics and antibacterial agents have shown that, except for chloramphenicol and co-trimixazole, passage through the blood-brain barrier is generally poor. However, when the meninges are inflamed therapeutically active concentrations of penicillins and of some cephalosporins can be measured in the CSF.