netilmicin and Acinetobacter-Infections

Single daily dosage of netilmicin is generally accepted in systemic infections, due to biphasic bactericidal activity and prolonged postantibiotic effect of aminoglycosides. Since little is known about the efficacy of single daily intraperitoneal application of netilmicin in the treatment of CAPD-associated peritonitis, we conducted this prospective study. Seven patients with CAPD-associated peritonitis were treated with a single daily dose of netilmicin (loading dose 1.5 mg/kg, followed by 40 mg/21 bag/day). Serum and intraperitoneal levels as well as bactericidal activity of netilmicin against Acinetobacter baumanii, E. coli and Pseudomonas aeruginosa were measured for 48 hours. Serum and peritoneal levels widely varied among the patients due to different interindividual plasma clearance of netilmicin. The intraperitoneal antibacterial action of netilmicin was decreased, more over, substantial differences in the bactericidal activity were found among the patients. However, with high initial netilmicin levels sufficient bactericidal activity was found for Acinetobacter and E. coli, but not for Pseudomonas aeruginosa. Hence, a single daily dosage of netilmicin can be a suitable treatment of CAPD-associated peritonitis, only if the dose is adapted according to the first serum and peritoneal levels. In infections with Pseudomonas aeruginosa higher peritoneal levels of netilmicin and the combination with other antibiotics will be needed for a sufficient peritoneal bactericidal activity.

Topics: Acinetobacter; Acinetobacter Infections; Adult; Aged; Drug Administration Schedule; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Netilmicin; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas Infections

We evaluated aminoglycoside resistance in 87 Acinetobacter baumannii strains isolated from four hospitals located in the North West region of Iran and typed them in sequence groups (SGs) using trilocus sequence-based scheme to compare their clonal relationships with international clones. Resistance toward aminoglycosides was assayed by minimum inhibitory concentration (MIC) and presence of aminoglycoside-modifying enzymes (AMEs), and ArmA-encoding genes were evaluated in different SGs. The majority of isolates belonged to SG1 (39%), SG2 (33.3%), and SG3 (12.6%), whereas the remaining ones were assigned to six novel variants of SGs. MIC determination revealed netilmicin as the most and kanamycin as the least active aminoglycosides against all groups. Among the varied SGs, isolates of SG2 showed more susceptibility toward all tested aminoglycosides. APH(3'')-VIa-encoding gene was predominant in SG1 (47%), SG2 (62%), and SG6-9 (100%). However, AAC(3')-Ia (100%) and ANT(2')-Ia (90.9%) were the dominant AMEs in SG3. There was significant association between harboring of aminoglycoside resistance genes and specific aminoglycosides: gene encoded by APH(3')-VIa was allied to resistance against amikacin and kanamycin, whereas ANT(2')-Ia was related to the resistance toward gentamicin and tobramycin in SG2. In SG1, tobramycin resistance was correlated with harboring of AAC(6')-Ib. Screening of armA demonstrated the presence of this gene in SG1 (58.8%), SG2 (10.3%), as well as SG3 (9%). Our results revealed definite correlation between the phenotypes and genotypes of aminoglycoside resistance in different clonal lineages of A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Clone Cells; Drug Resistance, Bacterial; Gene Expression; Gene Frequency; Genotype; Gentamicins; Hospitals; Humans; Iran; Kanamycin; Methyltransferases; Microbial Sensitivity Tests; Multilocus Sequence Typing; Netilmicin; Phenotype; Phylogeny; Tobramycin

Acinetobacter baumannii coccobacilli are dangerous to patients in intensive care units because of their multidrug resistance to antibiotics, developed mainly in the past decade. This study aimed to examine whether there is a significant correlation between the number of Pro-Ala repeats in the CAP01997 protein, the EmrA homologue of A. baumannii, and resistance to antibiotics. A total of 79 multidrug-resistant A. baumannii strains isolated from patients were analysed. Resistance to antibiotics was determined on Mueller-Hinton agar plates using the Kirby-Bauer disk diffusion method. The number of CCTGCA repeats encoding Pro-Ala repeats in CAP01997 was determined by PCR and capillary electrophoresis. The 3D models of CAP01997 containing Pro-Ala repeats were initially generated using RaptorX Structure Prediction server and were assembled with EasyModeller 4.0. The models were embedded in a model bacterial membrane based on structural information from homologous proteins and were refined using 100-ns molecular dynamics simulations. The results of this research show significant correlation between susceptibility to netilmicin, tobramycin and imipenem and the number of repeated Pro-Ala sequences in the CAP01997 protein, a homologue of the Escherichia coli transporter EmrA. Predicted structures suggest potential mechanisms that confer drug resistance by reshaping the cytoplasmic interface between CAP01997 protein and the critical component of the multidrug efflux pump homologous to EmrB. Based on these results, we can conclude that the CAP01997 protein, an EmrA homologue of A. baumannii, confers resistance to netilmicin, tobramycin and imipenem, depending on the number of Pro-Ala repeats.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Bacterial Proteins; Ceftazidime; Dipeptides; Drug Resistance, Multiple, Bacterial; Humans; Imipenem; Membrane Proteins; Microbial Sensitivity Tests; Models, Molecular; Netilmicin; Tobramycin

To assess the occurrence of the genes of the AdeABC efflux system and their association with antimicrobial resistance in Acinetobacter baumannii.. A set of 116 strains selected for their diversity both in genotypic properties and geographic origin was investigated for the presence of the structural (adeA, adeB and adeC) and regulatory (adeR and adeS) genes of the AdeABC system by PCR, for resistance to 11 antimicrobials by disc diffusion, for MIC of netilmicin and for the presence of aacC2 and aacA4, encoding netilmicin-modifying enzymes.. Ninety-five strains were positive for adeA, adeB, adeR and adeS, 10 were positive for 1 to 3 of these genes and 11 were negative for all genes. The adeC gene was found in 49 strains with one or more of the other genes. Forty-one strains were resistant to a maximum of one agent and 75 strains to two or more agents. Netilmicin MICs showed an almost bimodal distribution with respective peaks of 0.5-1 and 8 mg/L; aacC2 or aacA4 was found in six strains with netilmicin MIC of >or=64 mg/L. All 61 strains with netilmicin MICs >or= 4 mg/L were both adeABRS-positive and resistant to two or more agents, whereas netilmicin MICs

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; ATP-Binding Cassette Transporters; DNA Fingerprinting; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Genotype; Humans; Microbial Sensitivity Tests; Netilmicin; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Cerebral Hemorrhage; Cerebrospinal Fluid; Craniotomy; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Fatal Outcome; Female; Humans; Hydrocephalus; Injections, Spinal; Meningitis, Bacterial; Netilmicin; Ventriculoperitoneal Shunt

The effect of three aminoglycoside antibiotics--netilmicin (CAS 56391-57-2), gentamicin (CAS 1403-66-3) and amikacin (CAS 37517-28-5)--at subinhibitory concentrations (sub-MICs; 1/4 or 1/16 of the MICs) on the cytotoxic activity of Acinetobacter baumannii was studied. The cytotoxic factor was manifested by reduction of the number of isolated rat lung type II cells evaluated by alkaline phosphatase determination. All aminoglycosides at both concentrations studied (with the exception of 1/4 of the MIC of amikacin) did not modify cytotoxic activity of A. baumannii. This activity was partially inhibited only after treatment with amikacin at 1/4 of the MIC. In this case the number of type II cells after incubation with antibiotic treated A. baumannii was higher (71%) as compared to the number of type II cells cultured with untreated A. baumannii (47%).

Topics: Acinetobacter; Acinetobacter Infections; Amikacin; Animals; Anti-Bacterial Agents; Cell Survival; Cells, Cultured; Cytotoxins; Epithelial Cells; Gentamicins; Male; Microbial Sensitivity Tests; Netilmicin; Pulmonary Alveoli; Rats; Rats, Wistar