meropenem and Infant--Premature--Diseases

Prolonged infusion of meropenem has been suggested in studies with population pharmacokinetic modeling but has not been tested in neonates. We compared the steady-state pharmacokinetics (PK) of meropenem given as a short (30-min) or prolonged (4-h) infusion to very-low-birth-weight (gestational age, <32 weeks; birth weight, <1,200 g) neonates to define the appropriate dosing regimen for a phase 3 efficacy study. Short (n = 9) or prolonged (n = 10) infusions of meropenem were given at a dose of 20 mg/kg every 12 h. Immediately before and 0.5, 1.5, 4, 8, and 12 h after the 4th to 7th doses of meropenem, blood samples were collected. Meropenem concentrations were measured by ultrahigh-performance liquid chromatography. PK analysis was performed with WinNonlin software, and modeling was performed with NONMEM software. A short infusion resulted in a higher mean drug concentration in serum (C(max)) than a prolonged infusion (89 versus 54 mg/liter). In all but two patients in the prolonged-infusion group, the free serum drug concentration was above the MIC (2 mg/liter) 100% of the time. Meropenem clearance (CL) was not influenced by postnatal or postmenstrual age. In population PK analysis, a one-compartment model provided the best fit and the steady-state distribution volume (V(ss)) was scaled with body weight and CL with a published renal maturation function. The covariates serum creatinine and postnatal and gestational ages did not improve the model fit. The final parameter estimates were a V(ss) of 0.301 liter/kg and a CL of 0.061 liter/h/kg. Meropenem infusions of 30 min are acceptable as they balance a reasonably high C(max) with convenience of dosing. In very-low-birth-weight neonates, no dosing adjustment is needed over the first month of life.

Topics: Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Creatinine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Enterocolitis, Necrotizing; Female; Gram-Negative Bacteria; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Infusions, Intravenous; Male; Meropenem; Models, Statistical; Pneumonia; Sepsis; Software; Thienamycins

Meropenem was used in the treatment of 15 newborns (8 preterm) with sepsis, pneumonia or meningitis by intravenous infusion of 15-20 mg/kg daily divided to 3 equal doses. Clinical improvement was achieved in all the cases. No side effects were recorded.

Topics: Bacterial Infections; Dose-Response Relationship, Drug; Humans; Infant, Newborn; Infant, Premature, Diseases; Meningitis, Bacterial; Meropenem; Pneumonia, Bacterial; Sepsis; Thienamycins

Shunt infections are seen in 3% to 20% of patients who have cerebrospinal fluid (CSF) shunts. Although the staphylococcal species are the most common cause of shunt-related infections, Gram-negative bacteria are increasingly reported with higher mortality rates. Tigecycline, a glycylcycline, is not approved for children. But in the era of nosocomial infections due to multidrug-resistant pathogens, it can be the life-saving option. We report an infant with ventriculoperitoneal shunt-related meningitis treated with a tigecycline combination regimen. A 5-month-old boy who had a ventriculoperitoneal shunt was admitted with meningitis. Extended spectrum β-lactamase-producing Klebsiella pneumoniae grew in the CSF. At the end of the fourth week of intravenous meropenem plus gentamicin therapy, carbapenem-resistant K pneumoniae grew in the CSF (mean inhibitory concentration value for meropenem >4 μg/mL, by E-test). The infected shunt was removed, and an external ventricular drainage catheter was inserted. With permission, intravenous tigecycline (1.2 mg/kg per dose twice a day) and intrathecal amikacin were added to the meropenem. Intrathecal amikacin could be given for only 7 days. On the sixth day of tigecycline treatment, the CSF was sterilized. Antibiotic therapy was given and consisted of a total of 60 days of meropenem and 20 days of tigecycline therapy. Because no available efficacy and safety data from randomized-controlled studies exist, tigecycline must be used only as salvage therapy, in combination with other drugs, for critically ill children who have no alternative treatment options.

Topics: Amikacin; Drug Therapy, Combination; Humans; Hydrocephalus; Infant; Infant, Premature, Diseases; Infusions, Intravenous; Injections, Spinal; Klebsiella Infections; Klebsiella pneumoniae; Male; Meningitis, Bacterial; Meropenem; Microbial Sensitivity Tests; Minocycline; Off-Label Use; Salvage Therapy; Thienamycins; Tigecycline; Ventriculoperitoneal Shunt

Topics: Amikacin; Facial Dermatoses; Fatal Outcome; Female; Gangrene; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Meropenem; Necrosis; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Skin Diseases, Bacterial; Skin Ulcer; Thienamycins

Listeria monocytogenes, although an uncommon cause of illness in the general population, is an important pathogen in pregnants, neonates, elderly and immunocompromised patients. Neonatal listeriosis is classified as early (< 5 days) and late (? 5 days) according to the onset of the symptoms and findings of the infection. The most encountered serotypes in early neonatal listeriosis are 1a and 1b, while serotype 4a is more prevalent in the late form. In this report, a neonatal L.monocytogenes meningitis case developed in a female infant born after 36 weeks of gestation from a 29 years old mother, was presented. The newborn was hospitalized in intensive care unit because of low birth weight (1740 g) and prematurity. Due to the worsening of her general condition (feedings difficulty, tachypnea, high fever and bulging fontanel) on the 11th day, blood and cerebrospinal fluid (CSF) cultures were done. CSF culture yielded catalase positive, oxidase negative, gram-positive bacilli on the 4th day of cultivation. The isolate was identified as Listeria monocytogenes and found susceptible to all tested antibiotics (erythromycin, gentamicin, penicillin, trimethoprim sulphamethoxazole, vancomycin, teicoplanin) by automated identification and antibiogram system (VITEC 2, bioMérieux, France). The empirical treatment initiated with vancomycin and meropenem was changed to ampicillin and gentamicin and clinical and microbiological response was obtained. The isolate was serotyped as type 1/2b. No data related to maternal infection or environmental contamination were obtained from the studies investigating the origin of infection. There have been no reported cases of neonatal Listeria meningitis from Turkey in the avaliable literature. This was the first case of neonatal Listeria meningitis in our country and it was presented to withdraw attention to L.monocytogenes serotype 1/2b which was a rare cause of late onset neonatal listeriosis.

Topics: Ampicillin; Anti-Bacterial Agents; Cerebrospinal Fluid; Drug Therapy, Combination; Female; Gentamicins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Listeria monocytogenes; Meningitis, Listeria; Meropenem; Microbial Sensitivity Tests; Serotyping; Thienamycins; Vancomycin

We describe what we believe to be the first case of neonatal sepsis caused by CTX-M-producing Escherichia coli, in a low-weight preterm infant, born to a colonized mother who had received antibiotic treatment antepartum. Increased dissemination of extended-spectrum beta-lactamase-producing E. coli in the community should be borne in mind for empirical therapy of sepsis in high-risk newborns.

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Infectious Disease Transmission, Vertical; Male; Meropenem; Pregnancy; Pregnancy Complications, Infectious; Sepsis; Thienamycins