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International Journal of Clinical... Feb 2006The purpose of antibiotic treatment in pregnant women is to treat the mother and/or the fetus since it is known that antibiotics administered to the mother cross the... (Review)
Review
BACKGROUND
The purpose of antibiotic treatment in pregnant women is to treat the mother and/or the fetus since it is known that antibiotics administered to the mother cross the placenta and reach the fetus. A comparison of the drug concentration in maternal and fetal plasma gives an indication of the exposure of the fetus to the maternally administered antibiotics.
AIM
The aim of this study was to review the literature pertaining to the placental transfer of antibiotics in man and to classify the antibiotics according to the type of transfer involved. A table has been developed for use by physicians that lists the name of the antibiotic, the drug concentration in the cord and maternal plasma at delivery and the type of transfer involved.
METHODS
An initial medline search was performed with the key words "placental transfer of antibiotics" with the limit of "human". A second medline search was performed with the key words "placental transfer of..." followed by the class names of the antibiotic such as penicillins, cephalosporins, aminoglycosides, tetracyclines and macrolides. The bibliographic search on the placental transfer of antibiotics covered the period up to July 2005.
RESULTS
3 types of placental transfers were identified. A few antibiotics cross the placenta rapidly and equilibrate in the maternal and cord plasma; this type of transfer is termed "complete" and include the antibiotics ampicillin, methicillin, cefmenoxime and cefotiam. Antibiotics which show incomplete transfer to the placenta where concentrations are lower in the cord than maternal plasma are said to have "incomplete" transfer and these include azlocillin, dicloxacillin, piperacillin, sulbenicillin, cefoxitin, amikacin, gentamicin, kanamycin, streptomycin, fosfomycin, thiamphenicol, griseofulvin, vancomycin and colistimethate. Ceftizoxime is the only antibiotic so far known whose concentrations are higher in the cord than maternal plasma. This type of transfer is called "exceeding" transfer.
CONCLUSION
All examined antibiotics cross the human placenta including those with a molecular weight greater than 1000 kDa such as vancomycin and colistimethate but there are 3 distinct types of placental transfer: complete, incomplete and exceeding and most antibiotics exhibit incomplete transfer.
Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Female; Fetal Blood; Humans; Maternal-Fetal Exchange; Placenta; Pregnancy
PubMed: 16502764
DOI: 10.5414/cpp44057 -
Prikladnaia Biokhimiia I Mikrobiologiia 2005An indirect immunoassay for quantitative determination of ampicillin (range, 10-1000 ng/ml) in buffer or milk has been developed. Polyclonal antibodies were obtained...
An indirect immunoassay for quantitative determination of ampicillin (range, 10-1000 ng/ml) in buffer or milk has been developed. Polyclonal antibodies were obtained against ampicillin conjugated with bovine serum albumin; the conjugate was synthesized by direct condensation using carbodiimide. The antibodies were specific for ampicillin and exhibited low cross-reactivity to other penicillins (azlocillin, 17%; penicillin G, 10%; piperacillin, 5%; and carbenicillin, 4%). Matrix effects were minimized by combining the use of a casein-supplemented buffer (content of casein, 1%) with sample dilution. The threshold of ampicillin detection in milk (diluted tenfold) was equal to 5.0 ng/ml (which corresponded to 50 ng/ml of the original sample).
Topics: Ampicillin; Animals; Anti-Bacterial Agents; Antibodies; Antibody Specificity; Buffers; Cattle; Drug Residues; Immunoenzyme Techniques; Milk; Serum Albumin, Bovine
PubMed: 16358758
DOI: No ID Found -
Biophysical Journal Mar 2006To study translocation of beta-lactam antibiotics of different size and charge across the outer bacterial membrane, we combine an analysis of ion currents through single... (Comparative Study)
Comparative Study
To study translocation of beta-lactam antibiotics of different size and charge across the outer bacterial membrane, we combine an analysis of ion currents through single trimeric outer membrane protein F (OmpF) porins in planar lipid bilayers with molecular dynamics simulations. Because the size of penicillin molecules is close to the size of the narrowest part of the OmpF pore, penicillins occlude the pore during their translocation. Favorably interacting penicillins cause time-resolvable transient blockages of the small-ion current through the channel and thereby provide information about their dynamics within the pore. Analyzing these random fluctuations, we find that ampicillin and amoxicillin have a relatively high affinity for OmpF. In contrast, no or only a weak interaction is detected for carbenicillin, azlocillin, and piperacillin. Molecular dynamics simulations suggest a possible pathway of these drugs through the OmpF channel and rationalize our experimental findings. For zwitterionic ampicillin and amoxicillin, we identify a region of binding sites near the narrowest part of the channel pore. Interactions with these sites partially compensate for the entropic cost of drug confinement by the channel. Whereas azlocillin and piperacillin are clearly too big to pass through the channel constriction, dianionic carbenicillin does not find an efficient binding region in the constriction zone. Carbenicillin's favorable interactions are limited to the extracellular vestibule. These observations confirm our earlier suggestion that a set of high-affinity sites at the narrowest part of the OmpF channel improves a drug's ability to cross the membrane via the pore.
Topics: Anti-Bacterial Agents; Computer Simulation; Escherichia coli; Ion Channel Gating; Lipid Bilayers; Membrane Fluidity; Models, Biological; Models, Chemical; Penicillins; Porins; Porosity; Static Electricity; beta-Lactams
PubMed: 16339889
DOI: 10.1529/biophysj.105.075192 -
Revista Panamericana de Salud Publica =... Nov 2004To assess the effectiveness of combined therapy with azlocillin and amikacin in a group of neonates with sepsis caused by multiresistant staphylococci who were... (Comparative Study)
Comparative Study
OBJECTIVE
To assess the effectiveness of combined therapy with azlocillin and amikacin in a group of neonates with sepsis caused by multiresistant staphylococci who were hospitalized in the neonatal intensive care unit of Hospital Ginecobstétrico "America Arias" in Havana, Cuba, from 1998 to 2000.
METHODS
A retrospective study was carried out of the clinical and laboratory results obtained in 15 patients with sepsis caused by multiresistant staphylococci who received combined therapy with azlocillin and amikacin, according to hospital guidelines on the use of antibiotics. We used a broth microdilution method to study the patterns of resistance shown by isolated strains to 10 of the antibiotics in use. In vitro synergy tests, specifically the checkerboard technique with microtitration plates, were used to observe the effects of treatment in 8 patients.
RESULTS
Twelve coagulase-negative staphylococci and three Staphylococcus aureus isolates showed five different patterns of resistance on the basis of their sensitivity to oxacillin, three aminoglycosides, and vancomycin. Six of the synergy tests showed a considerable synergistic effect, with an average three-fold reduction in the minimum inhibitory concentrations (MIC) of the two antibiotics used to treat the patients. No antagonistic effects were noted, and the combined antibiotics showed an overall clinical effectiveness of 91.7%.
CONCLUSIONS
The test showed that the therapeutic combination used was effective, but further studies are needed before conclusive results are obtained.
Topics: Amikacin; Anti-Bacterial Agents; Azlocillin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Microbial Sensitivity Tests; Models, Theoretical; Retrospective Studies; Sepsis; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus
PubMed: 15729980
DOI: 10.1590/s1020-49892004001100004 -
Antimicrobial Agents and Chemotherapy Feb 2005Penicillin-binding proteins (PBPs) catalyze the essential reactions in the biosynthesis of cell wall peptidoglycan from glycopeptide precursors. beta-Lactam antibiotics...
Penicillin-binding proteins (PBPs) catalyze the essential reactions in the biosynthesis of cell wall peptidoglycan from glycopeptide precursors. beta-Lactam antibiotics normally interfere with this process by reacting covalently with the active site serine to form a stable acyl-enzyme. The design of novel beta-lactams active against penicillin-susceptible and penicillin-resistant organisms will require a better understanding of the molecular details of this reaction. To that end, we compared the affinities of different beta-lactam antibiotics to a modified soluble form of a resistant Enterococcus faecium PBP5 (Delta1-36 rPBP5). The soluble protein, Delta1-36 rPBP5, was expressed in Escherichia coli and purified, and the NH(2)-terminal protein sequence was verified by amino acid sequencing. Using beta-lactams with different R1 side chains, we show that azlocillin has greater affinity for Delta1-36 rPBP5 than piperacillin and ampicillin (apparent K(i) = 7 +/- 0.3 microM, compared to 36 +/- 3 and 51 +/- 10 microM, respectively). Azlocillin also exhibits the most rapid acylation rate (apparent k(2) = 15 +/- 4 M(-1) s(-1)). Meropenem demonstrates an affinity for Delta1-36 rPBP5 comparable to that of ampicillin (apparent K(i) = 51 +/- 15 microM) but is slower at acylating (apparent k(2) = 0.14 +/- 0.02 M(-1) s(-1)). This characterization defines important structure-activity relationships for this clinically relevant type II transpeptidase, shows that the rate of formation of the acyl-enzyme is an essential factor determining the efficacy of a beta-lactam, and suggests that the specific side chain interactions of beta-lactams could be modified to improve inactivation of resistant PBPs.
Topics: Acylation; Algorithms; Anti-Bacterial Agents; Azlocillin; Binding Sites; Carbapenems; Drug Resistance, Bacterial; Enterococcus faecium; Kinetics; Meropenem; Models, Molecular; Penicillin G; Penicillin-Binding Proteins; Peptidyl Transferases; Plasmids; Structure-Activity Relationship; Thienamycins
PubMed: 15673741
DOI: 10.1128/AAC.49.2.612-618.2005 -
Antimicrobial Agents and Chemotherapy Dec 2004As part of the SENTRY Antimicrobial Surveillance Program in 2002, five multidrug-resistant Pseudomonas aeruginosa clinical isolates were detected with...
As part of the SENTRY Antimicrobial Surveillance Program in 2002, five multidrug-resistant Pseudomonas aeruginosa clinical isolates were detected with metallo-beta-lactamase (MbetaL) activity. The isolates were recovered from different patients in a medical center located in Dusseldorf, Germany. The resistant determinant was isolated amplifying the region between the integrase and the aacA4 gene cassette. Sequencing revealed a novel MbetaL gene, designated bla(GIM-1). Additional analysis showed that GIM-1, comprising 250 amino acids and with a pI value of 5.4, differs in its primary sequence from that described for IMP, VIM, and SPM-1 enzymes by 39 to 43%, 28 to 31%, and 28%, respectively. The enzyme possesses unique amino acids within the major consensus sequence (HXHXD) of the MbetaL family. Kinetics analysis revealed that GIM-1 has no clear preference for any substrate and did not hydrolyze azlocillin, aztreonam, and the serine-beta-lactamase inhibitors. bla(GIM-1) was found on a 22-kb nontransferable plasmid. The new MbetaL gene was embedded in the first position of a 6-kb class 1 integron, In77, with distinct features, including an aacA4 cassette downstream of the MbetaL gene that appeared to be truncated with bla(GIM-1). The aacA4 was followed by an aadA1 gene cassette that was interrupted by a copy of the IS1394. This integron also carried an oxacillinase gene, bla(OXA-2), before the 3'-CS region. GIM-1 appears to be a unique MbetaL, which is located in a distinct integron structure, and represents the fourth subclass of mobile MbetaL enzymes to be characterized.
Topics: Amino Acid Sequence; Carbapenems; DNA Primers; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Agar Gel; Electrophoresis, Gel, Pulsed-Field; Genes, Bacterial; Integrons; Isoelectric Focusing; Kinetics; Microbial Sensitivity Tests; Molecular Sequence Data; Phenotype; Pseudomonas aeruginosa; Reverse Transcriptase Polymerase Chain Reaction; beta-Lactamases
PubMed: 15561840
DOI: 10.1128/AAC.48.12.4654-4661.2004 -
Naunyn-Schmiedeberg's Archives of... May 2004Although the consumption of tea has been associated with beneficial cardiovascular effects, (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin in this...
Although the consumption of tea has been associated with beneficial cardiovascular effects, (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin in this beverage has shown seemingly contradictory actions on vascular tissues, for example vasorelaxant activity that could contribute favourably to prevention of cardiovascular disease, and contractile activity that could act in the opposite direction. The purpose of the present work was to study the contractile effects of EGCG on isolated rat thoracic aorta rings and its effects on the cytosolic free [Ca(2+)] ([Ca(2+)](i)) measured with fura-2 in cultured rat aortic smooth muscle cell line. In partially depolarised (15 mM KCl) aortic rings EGCG (30-300 microM), (+/-)-BAY K 8644 (0.1 microM) and thapsigargin (1 microM) induced a Ca(2+)-dependent, endothelium-independent contraction associated with [Ca(2+)](i) elevation in RASMC. EGCG enhanced the responses elicited by (+/-)-BAY K 8644 and thapsigargin both in aortic rings and in RASMC. Nifedipine totally inhibited the (+/-)-BAY K 8644-induced contraction, but only partially blocked the contractile responses to EGCG and thapsigargin, while SKF 96365 abolished both responses. The effects of these channel blockers were associated with a decrease in [Ca(2+)](i) in RASMC. Re-introduction of Ca(2+) in the medium after depletion of intracellular Ca(2+) stores with thapsigargin in a Ca(2+)-free solution elicited a contraction of aortic rings and an increase in [Ca(2+)](i) in RASMC. In both cases, this response was partially sensitive to nifedipine, abolished by SKF 96365 and clearly enhanced by EGCG. These results suggest that EGCG induces a transient endothelium-independent contraction in the rat aorta, probably by increasing smooth vascular cell membrane permeability to Ca(2+) through both non-specific and dihydropyridine-sensitive Ca(2+) channels.
Topics: Animals; Antioxidants; Aorta; Azlocillin; Calcium; Catechin; Drug Synergism; Imidazolidines; Male; Muscle, Smooth, Vascular; Rats; Rats, Inbred WKY; Thapsigargin; Vasoconstriction; Vasodilator Agents
PubMed: 15083267
DOI: 10.1007/s00210-004-0923-8 -
Journal of Microbiological Methods Feb 2004C(18)-carboxypropylbetaine (CB-18) specimen processing has enhanced the diagnosis of mycobacterioses by smear, culture, and nucleic acid amplification. However, toxic...
Characterization of the susceptibility of mycobacteria in BACTEC 12B media containing PANTA that had been supplemented with ceftazidime, and characterization of the individual components of PANTA in the presence of C18-carboxypropylbetaine.
C(18)-carboxypropylbetaine (CB-18) specimen processing has enhanced the diagnosis of mycobacterioses by smear, culture, and nucleic acid amplification. However, toxic side effects of CB-18 in liquid culture, especially in the presence of antibiotics, have been reported. The interaction of CB-18 at 20-25 microg/ml with the individual components of the antibiotic supplement PANTA that had been fortified with ceftazidime (PANTA-caz) was characterized in BACTEC 12B cultures using four mycobacterial isolates. When the Mycobacterium tuberculosis isolate ATCC 27294 was examined CB-18 plus PANTA-caz did not significantly alter the time-to-positive (i.e., time to a growth index (GI) of 15 (GI(15))), but did significantly increase the time to a GI of 500 (GI(500)) by approximately 8.5 days. This result could be attributed primarily to nalidixic acid, but also to ceftazidime to a lesser degree. Statistically significant increases in GI(15) of 12.5 days and GI(500) of 16.5 days were observed in the presence of CB-18 plus PANTA-caz with the Mycobacterium avium isolate ATCC 25291. These increases were due exclusively to trimethoprim. Statistically significant increases of approximately 2.5 and 9 days in GI(15) and GI(500), respectively, were observed with Mycobacterium kansasii ATCC 12478 in CB-18 plus PANTA-caz. The presence of nalidixic acid and ceftazidime were responsible for these alterations. When the behavior of the Mycobacterium fortuitum isolate ATCC 6841 was investigated in CB-18 plus PANTA-caz, significant increases in GI(15) of 8.5 days and GI(500) of 13 days were observed. The additive effects of nalidixic acid and azlocillin were responsible for these results. No single component of the PANTA-caz formulation was responsible for the interaction between CB-18 and PANTA-caz, although nalidixic acid contributed to these effects most often. These findings are consistent with the previous recommendation that CB-18 specimen processing follow a dilution-based format to ensure that the concentration of CB-18 carried-over into liquid media falls below 5-10 microg/ml.
Topics: Anti-Bacterial Agents; Azlocillin; Bacteriological Techniques; Betaine; Ceftazidime; Culture Media; Mycobacterium; Nalidixic Acid; Polymyxin B; Trimethoprim
PubMed: 14744453
DOI: 10.1016/j.mimet.2003.10.020 -
Journal of Chemotherapy (Florence,... Oct 2003The natural susceptibility of 20 Ewingella americana strains to 72 antibiotics was examined. MIC values were determined using a microdilution procedure in...
The natural susceptibility of 20 Ewingella americana strains to 72 antibiotics was examined. MIC values were determined using a microdilution procedure in cation-adjusted Mueller-Hinton broth. Evaluation of natural antibiotic susceptibility was performed applying the German standard (where applicable). Beta-lactamases were examined with a conventional nitrocefin colony testing procedure, activity and induction assays, and SDS-PAGE. Ewingella strains were naturally resistant or of intermediate susceptibility to cefaclor, loracarbef, cefazoline, cefuroxime, cefoxitin, benzylpenicillin, oxacillin, fosfomycin, erythromycin, roxithromycin, clarithromycin, lincosamides, dalfopristin-quinupristin, ketolides, linezolid, glycopeptides, fusidic acid and rifampicin. Uniform natural sensitivity was found with acylureidopenicillins except for azlocillin, ticarcillin, several cephalosporins, carbapenems, aztreonam, tetracyclines, aminoglycosides, quinolones, azithromycin, folate-pathway inhibitors and chloramphenicol. Strains of E. americana were naturally sensitive or of intermediate susceptibility to aminopenicillins (with and without beta-lactamase inhibitors), azlocillin and nitrofurantoin. All ewingellae yielded beta-lactamases; testing of representative strains revealed that these enzymes belong to Ambler class C. Inducibility of beta-lactamase was shown for E. americana ATCC 33852T, CCUG 35675 and CCUG 42782. The present study describes a database concerning the natural susceptibility of E. americana strains to a range of antibiotics, which can be applied to validate forthcoming antibiotic susceptibility tests of these bacteria. It enlarges the number of Enterobacteriaceae expressing naturally-occurring AmpC beta-lactamases.
Topics: Databases, Factual; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Microbial Sensitivity Tests
PubMed: 14598935
DOI: 10.1179/joc.2003.15.5.428 -
Letters in Applied Microbiology 2003The study evaluated the efficacy of four Mycobacterium avium subsp. paratuberculosis (MAP) culture media in suppressing commonly used starter cultures and typical...
AIMS
The study evaluated the efficacy of four Mycobacterium avium subsp. paratuberculosis (MAP) culture media in suppressing commonly used starter cultures and typical nonstarter microflora present during the manufacture and ripening of Cheddar cheese, with a view to identify a suitable medium for the enumeration of MAP during laboratory-scale Cheddar production.
METHODS AND RESULTS
Four Cheddar starter cultures and Cheddar cheese manufactured with these starters were inoculated onto Herrold's egg yolk medium (HEYM); HEYM supplemented with vancomycin, amphotericin B and nalidixic acid (HEYM/VAN); Middlebrook 7H10 agar containing polymyxin, amphotericin B, nalidixic acid, trimethoprim and azlocillin (PANTA) antibiotic supplement; and BACTEC 12B radiometric medium with and without a preliminary decontamination step (0.75% w/v hexadecylpyridinium chloride (HPC), 5 h). The inclusion of a decontamination step inhibited all Cheddar cheese starter and nonstarter micro-organisms. The medium 7H10/PANTA and to a lesser extent HEYM/VAN were effective inhibitors of cheese microflora when no decontamination step was employed.
CONCLUSIONS
Middlebrook 7H10 medium, supplemented with PANTA antibiotics, suppressed all micro-organisms associated with ripening Cheddar cheese manufactured with pasteurized milk.
SIGNIFICANCE AND IMPACT OF THE STUDY
A MAP culture medium has been identified, which may be used to enumerate this bacterium during the laboratory manufacture and ripening of Cheddar cheese and hence facilitate further research into the persistence of this pathogen in the product.
Topics: Animals; Bacteriological Techniques; Cheese; Colony Count, Microbial; Culture Media; Mycobacterium avium subsp. paratuberculosis
PubMed: 12969490
DOI: 10.1046/j.1472-765x.2003.01392.x