Effect of alternative antibiotics in treatment of cefotaxime resistant spontaneous bacterial peritonitis

AIM:To evaluate effective alternative antibiotics in treatment of cefotaxime-resistant spontaneous bacterial peritonitis.METHODS:One hundred cirrhotic patients with spontaneous bacterial peritonitis [ascitic fluid polymorphonuclear cell count(PMNLs) ≥ 250 cells/mm 3 at admission] were empirically treated with cefotaxime sodium 2 g/12 h and volume expansion by intravenous human albumin.All patients were subjected to history taking,complete examination,laboratory tests(including a complete blood cell count,prothrombin time,biochemical tests of liver and kidney function,and fresh urine sediment),chest X-ray,a diagnostic abdominal paracentesis,and the sample subjected to total and differential cell count,chemical examination,aerobic and anaerobic cultures.Patients were divided after 2 d by a second ascitic PMNL count into group Ⅰ;patients sensitive to cefotaxime(n = 81),group Ⅱ(n = 19);cases resistant to cefotaxime(less than 25% decrease in ascitic PMNL count).Patients of group Ⅱ were randomly assigned into meropenem(n = 11) or levofloxacin(n = 8) subgroups.All patients performed an end of treatment ascitic PMNL count.Patients were considered improved when:PMNLs decreased to < 250 cells/mm 3,no growth in previously positive culture cases,and improved clinical manifestations with at least 5 d of antibiotic therapy.RESULTS:Age,sex,and Child classes showed no significant difference between group Ⅰ and group Ⅱ.Fever and abdominal pain were the most frequent manifestations and were reported in 82.7% and 80.2% of patients in group Ⅰ and in 94.7% and 84.2% of patients in group Ⅱ,respectively.Patients in group Ⅱ had a more severe ascitic inflammatory response than group Ⅰ and this was demonstrated by more ascitic lactate dehydrogenase(LDH) [median:540 IU/L(range:150-1200 IU/L) vs median:240 IU/L(range:180-500 IU/L),P = 0.000] and PMNL [median:15 000 cell/mm 3(range:957-23 822 cell/mm 3) vs 3400 cell/mm 3(range:695-26 400 cell/mm 3),P = 0.000] counts.Ascitic fluid culture was positive in 32% of cases.Cefotaxime failed in 19% of patients;of these patients,11(100%) responded to meropenem and 6(75%) responded to levofloxacin.Two patients with failed levofloxacin therapy were treated according to the in vitro culture and sensitivity(one case was treated with vancomycin and one case was treated with ampicillin/sulbactam).In group Ⅱ the meropenem subgroup had higher LDH(range:108-860 IU/L vs 120-491 IU/L,P = 0.042) and PMNL counts(range:957-23 822 cell/mm 3 vs 957-15 222 cell/mm 3,P = 0.000) at initiation of the alternative antibiotic therapy;there was no significant difference in the studied parameters between patients responsive to meropenem and patients responsive to levofloxacin at the end of therapy(mean ± SD:316.01 ± 104.03PMNLs/mm 3 vs 265.63 ± 69.61 PMNLs/mm 3,P = 0.307).The isolated organisms found in group Ⅱ were;enterococci,acinetobacter,expanded-spectrum β-lactamase producing Escherichia coli,β-lactamase producing Enterobacter and Staphylococcus aureus.CONCLUSION:Empirical treatment with cefotaxime is effective in 81% of cases;meropenem is effective in cefotaxime-resistant cases.

In vitro interference of cefotaxime at subinhibitory concentrations on biofilm formation by nontypeable Haemophilus influenzae

Objective:To investigate the in vitro interference of cefotaxime at subinhibitory concentrations [sub-minimal inhibitory concentrations(MIC)] on biofilm formation by nontypeable Haemophilus influenzae(NTHi).Methods:The interference of subinhibitory concentrations of cefotaxime on biofilm formation of the clinical strong-biofilm forming isolates of NTHi was evaluated by a microtiter plate biofilm formation assay.The effect of sub-MIC cefotaxime on bacterial cell-surface hydrophobicity was determined using a standard microbial adhesion to n-hexadecane test.Additionally,the effects on bacterial adherence to human fibronectin and expression of bacterial adhesins were also investigated.Results:Subinhibitory concentrations of cefotaxime,both at 0.1× and 0.5× MIC levels,efficiently reduced the NTHi biofilm formation,and this effect was independent of decreasing bacterial viability.Sub-MIC cefotaxime also decreased bacterial cell-surface hydrophobicity and reduced adherence to human fibronectin.Inhibition in the P2 and P6 gene expressions upon exposure to sub-MIC cefotaxime was also noted.Conclusions:Taken together,our results indicate that sub-MIC cefotaxime interferes with the formation of NTHi biofilm,and this effect is feasibly related to the interference with cell-surface hydrophobicity,fibronectin-binding activity as well as alteration of the P2 and P6 gene expression.The findings of the present study therefore provide a rationale for the use of subinhibitory concentrations of cefotaxime for treatment of NTHi-related diseases.

Study on the effects of cefotaxime on intracellular Ca^(2+) in human peripheral lymphocytes by fluoremetry

Characteristic of Fura-2-Ca^2＋ interaction was studied based on the fluorescence technique. The apparent dissociation constants （Kd） of the Fura-2-Ca^2＋ complex were determined at different temperature. The effect of cefotaxime （CEFA） on intracellular Ca^2＋ concentration （[Ca^2＋]i） was discussed by using a ratiometric fluorescence dye Fura-2 as a probe. The basal [Ca^2＋]i in resting human peripheral lymphocytes was 100 4- 7 nmol/L but after treatment with cefotaxime, the changes of [Ca^2＋]i were observed in different conditions. In the concentration range of 1-30 μmol/L of cefotaxime [Ca^2＋]i increased, as a result of releasing intracellular Ca^2＋ stores. Higher concentration of cefotaxime （50-500 μmol/L） stimulated to decrease of [Ca^2＋]i.

The Stimulatory Effects of the Antimicrobial Agents Bavistin, Cefotaxime and Kanamycin on <i>In Vitro</i>Plant Regeneration of <i>Centella asiatica</i>(L.)—An Important Antijaundice Medicinal Plant

Antimicrobial agents such as bavistin, cefotaxime and kanamycin were evaluated for their effects on the rapid shoot regeneration from nodal explants of Centella asiatica (L.). Filter sterilized bavistin (250 mg/L) was augmented alone and in combination with cytokinins such as BAP and TDZ into the media to trace the effect on regeneration. On this basis, the potential use of bavistin (150 mg/L) along with BAP (2.0 mg/L) was evaluated which showed the maximum shoot number (6.6) and shoot length (4.4 cm) respectively. Cefotaxime at the concentration of 100 μM/L was found to be effective to obtain the maximum shoot number formation (5.8) with the regeneration frequency (90%). Kanamycin at the concentration of 80 μM/L induced maximum shoot regeneration (5.12). Kanamycin at 100 μM/L or at higher concentrations reduced the shoot regeneration. The best rooting response was noticed when in vitro regenerated microshoots were transferred to the rooting medim which was supplemented with IBA (2.0 mg/L). This combination generates 90% of regeneration frequency and maximum number of roots per shoot (14.2) and high root length (4.2 cm). The rooted plants were acclimatized and transferred to field for survivalance. The addition of antibiotics was found to be more effective and safer for using since their effects on regeneration were found to be negligible.

Complexity of Gold(Ⅲ)Ion With Cefotaxime and Cefepime Drugs:Spectroscopic,Antimicrobial and Antitumor Discussions

The availability of chemical and biological data presented in this paper is the basis for understanding not only the current state of anti-cancer drugs based on gold(Ⅲ),but also the rationale for strategies for future drug design.New Au(Ⅲ)nanosized complexes of cefotaxime(ceph-3)and cefepime(ceph-4)ligands as a 3rd and 4th of cephalosporin generation drugs were synthesized.Gold(Ⅲ)complexes were discussed based on the elemental,molar conductance,thermal and magnetic moment measurements as well as spectral(FTIR,1HNMR,UV-Vis,and XRD)techniques.FT-IR spectra revealed that the ceph-3 and ceph-4 ligands reacted as a bidentate ligands through carboxylate oxygen andβ-lactam oxygen groups.The analytical analysis confirm that the molar ratio is 1∶1(Au 3+/ceph)with general formula[Au(L)(Cl)2]where L=ceph-3 or ceph-4.The structures of Au(Ⅲ)complexes were presence as a square planar geometry.X-ray diffraction patterns referred to a crystalline nature for all synthesized complexes.TEM analyses confirmed that the synthetic gold(Ⅲ)complexes have a nanosized particles.In vitro antimicrobial activities of Au(Ⅲ)complexes were evaluated towards two types of bacteria(G+&G-).The antitumor activities of gold(Ⅲ)complexes are appraised against breast(MCF-7)and colorectal adenocarcinoma(Caco-2)cell lines,which means that the two complexes may consider promising anticancer drugs.

第三代半合成头孢菌素:Cefoperazone、Cefotaxime和Moxalactam

近年来半合成头孢菌素获得迅速的发展,并根据抗菌谱的范围已进入第四世代的研究。抗菌谱与头孢噻嗯相似的称为第一代;第二代抗菌谱除包括第一代范围外扩大至对第一代无效的肠杆菌属、吲哚阳性变形菌属、嗜血流感杆菌和某些拟杆菌属等;第三代活力更高,抗菌谱更广,并包括绿脓杆菌。目前正在发展药物动力学性能更优的第四代。本文就第三代中几个较成熟的半合成头孢菌素概述于下。头孢氧哌唑(Cefoperazone,T-1551)

Synthesis and Characterization of Schiff Base Metal Complexes Derived from Cefotaxime with 1<i>H</i>-indole-2,3-dione (Isatin) and 4-N,N-dimethyl-aminobenzaldehyde

This work involved the synthesis of two Schiff base derivatives of cefotaxime antibiotic (CFX) namely: [sodium3-(acetoxymethyl)-7-((Z)-2-(methoxyimino)-2-(2-((E)-2–oxoindolin-3-ylide-neamino) thiazol-4-yl)acetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate]. (0.5) Methanol (LI) and [sodium3-(acetoxymethyl)-7-((2Z)-2-(2-(4-dimethylamino) benzylideneamino) thiazol-4-yl)-2-(methoxyimino)acetamido)-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylate]. (0.5) Methanol (LII) from the condensation reaction of the antibiotic with 1H-Indole-2,3-dione(isatin) and -N, N-dimethyl amino benzaldehyde respectively. Metal complexes of the two Schiff base ligands with Co(II), Ni(II), Cu(II), Cd(II), Pd(II) and Pt(IV) ions were prepared by reacting each ligand with the metal salts in refluxing ethanol. The chemical structures of the two ligands as well as the stereo-chemical structures and geometries of the studied metal complexes were suggested depending the results obtained from CHN and TG analysis, NMR, FTIR, and atomic absorption spectrophotometry, electronic spectra, magnetic moments and conductivity measurements. The mole ratio of the ligands to the metal ion was 1:1 with tridentate bonding behaviors of the coordinating ligands with the metal ions.

Antibiosis of Cefotaxime/Clindamycin and Lactobacillus acidophilus on Related Bacteria to Diabetic Foot Ulcer

Diabetic foot complications are very common and represent a serious health problem in Mexico because of their high frequency, high costs and difficulties in handling. The treatment of choice to inhibit bacteria related to diabetic foot ulcer consists mainly of the use of cefotaxime however the problem with this treatment (antibiotics) is not always effective due to the pathophysiological condition of the patient, together with the resistance bacteria develop to the drugs. OMS has suggested the use of probiotics for research directed to the development of microbial interference therapies. This project used the Lyophilized conditioned medium with probiotics, extracellulars of probiotics, because there are reports in which wound healing in mice is observed employing probiotics. The objective of this study was to evaluate the biological activity of cefotaxime, clindamycin and thelyophilized conditioned media Lactobacillus acidophilus (LCMLa) on bacterias isolated from diabetic foot ulcer, this bioassay was performed by the turbidimetric method. The macroscopic analysis of the colonies was carried out and the morphological analysis of the bacteria was carried out using the atomic force microscope;in addition, the type of Gram and oxygen requirements for its growth were determined. From the diabetic foot ulcers, three strains were isolated, of which strain 1 and 3 whose morphology corresponds to a bacillus, was susceptible to cefotaxime and to the lyophilized conditioned medium of L. acidophilus. The potential of microbial interference that exhibits L. acidophilus on bacteria related to diabetic foot ulcer is demonstrated.

Nano-Coupling of Cephalosporin Antibiotics with Fe<SUB>3</SUB>O<SUB>4</SUB>Nanoparticles: Trojan Horse Approach in Antimicrobial Chemotherapy of Infections Caused by <i>Klebsiella spp</i>.

In the present study we had an aim to develop the methods of functionalizing the surface of magnetite nanoparticles with cefotaxime and ceftriaxone antibiotics. The quantitative analysis of the nanostructured cephalosporins was determined by Atom Absorbance Spectroscopy (AAS) and based on the Lambert-Beer law. The engineered nanostructures were tested on gram-negative microorganisms Klebsiella spp., of Enterobacteriaceae, and gram-positive bacteria Staphylococcus aureus, each having multi-drug resistance properties.

Development of Sanitation Protocol for Leaf Explants of <i>B. huillensis</i>for <i>in Vitro</i>Culture

Brachylaena huillensis (Silver Oak) is a multipurpose timber tree species in the family of Asteraceae. There has been a very high demand for B. huillensis wood and its products leading to overexploitation. B. huillensis regenerates through seedlings. However, it produces seeds with poor germination. Seeds are also difficult to be collected because of small size. Many are eaten by insects and currently there is a lack of seed bank. The facts that have hindered and rendered the natural regeneration of the tree species were uncertain. The present investigation was carried out to develop sanitation protocol of B. huillensis using leaves as explants. Juvenile leaves from the tips of B. huillensis naturally growing seedlings were collected from Bombo West Forest Reserve in Tanzania. The leaves were washed and immersed in NaOCL containing various concentrations levels and two drops of tween 20. There was significant difference between the concentrations levels employed. However, the best results were obtained when leaf explants were immersed in 1.5% v/v NaOCL for ten minutes and later in ethanol for ten seconds and cultured on woody plant media medium containing antifungal (cefotaxime). Genuinely, the protocol is vital and so opens up the way for other subsequent stages for in vitro propagation of B. huillensis.

Genetic Transformation of <i>Citrus sinensis</i>L. with an <i>antisense ACC oxidase</i>Gene

This work was carried out to optimize the conditions for highly effective embryogenic callus induction from mature seeds, plantlet regeneration and genetic transformation of Citrus sinensis L. by Agrobacterium tumefaciens strain EHA105 (pCAMBIA 1305.1). Embryogenic calli could be successfully induced from mature seeds employing the MT medium supplemented with 500 mg/l malt extract. The percentage of embryogenic callus induction was 85. With the same medium, the high proliferation rate of embryogenic callus was achieved. The liquid MT medium containing 500 mg/l malt extract in combination with 50 mg/l lactose could be used as the embryoid development medium. Somatic embryos, however, could be regenerated with normal shoots and roots in the MS medium, with the regeneration percentage of 60. The delivery of an antisense ACC oxidase gene into the species C. sinensis mediated by Agrobacterium tumefaciens strain EHA 105 was successful by co-cultivating explants with the strain EHA 105 for 10 min, following that by eliminating the bacterium with 200 mg/l cefotaxime, and subsequently selecting transformed embryoid with 20 mg/l hygromycin. Verified histochemically by GUS assay, putative transformants showed the percentage of gus gene expression of 100. Molecular analysis using PCR confirmed the integration of the antisense ACC oxidase gene into plant genome.

Antibacterial activity of Valeriana jatamansi against extended-spectrum β-lactamase producing Gram-negative bacteria causing urinary tract infections

Objective:To find out the antibacterial activity of Valeriana jatamansi(V.jatamansi)rhizomes against the extended-spectrumβ-lactamases(ESBLs)producing isolates of Enterobacteriaceae family.Methods:Confirmation of ESBLs producing Escherichia coli,Enterobacter aerogenes,Klebsiella pneumoniae and Hafnia alvei isolated from urinary tract infections was performed by double disc diffusion assay.Antimicrobial susceptibility of all ESBLs producing isolates was determined by disc diffusion method following guidelines of Clinical and Laboratory Standards Institute.Successive extraction of rhizomes of V.jatamansi was performed with hexane,chloroform and methanol using Soxhelt apparatus.These extracts were tested against the ESBLs producing isolates using well diffusion method.Results:Hexane extract showed significant results as compared to chloroform and methanol extracts with the maximum zone of inhibition(21 mm)while ciprofloxacin and amikacin were used as standard drugs.Conclusions:Findings of the study suggested that hexane extract of V.jatamansi can be used in combination with other antibiotics as alternative treatment for urinary tract infections caused by ESBLs producing strains of Enterobacteriaceae.