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PubMed1977

Binding of thienamycin and clavulanic acid to the penicillin-binding proteins of Escherichia coli K-12.

Thienamycin and clavulanic acid are new beta-lactam derivatives with structures markedly different from those of penicillins or cephalosporins. Both derivatives had the same general mode of action as typical beta-lactam antibiotics since they bound to precisely the same proteins as [(14)C]benzylpenicillin. Thienamycin showed high affinity for penicillin-binding proteins 1, 2, 4, 5, and 6 and a lower affinity for protein 3. Protein 2 had the highest affinity for thienamycin, and concentrations from the minimal morphological change concentration (0.1 mug/ml) up to about 0.6 mug/ml resulted in the conversion of Escherichia coli KN126 into large osmotically stable round cells. Above a concentration of 0.6 mug/ml, rapid cell lysis occurred with the release of the cell contents as spheroplasts. Clavulanic acid showed good affinity for penicillin-binding protein 2, moderate affinity for proteins 1, 4, 5, and 6, and low affinity for protein 3. Protein 2 had the highest affinity for clavulanic acid, and concentrations from the minimal morphological change concentration (30 mug/ml) up to about 50 mug/ml produced a mixture of slightly elongated, swollen, bulging, and lemon-shaped cells. Above a concentration of 50 mug/ml, rapid lysis occurred with production of spheroplasts. The properties of thienamycin and clavulanic acid were compared with those of the penicillins, cephalosporins, and amidinopenicillanic acids.

Anti-Bacterial Agents↗
PubMed1979

Thienamycin: new beta-lactam antibiotic with potent broad-spectrum activity.

Thienamycin, a new beta-lactam antibiotic, exhibited potent, broad-spectrum activity in vitro against gram-negative bacilli and gram-positive cocci, including many isolates resistant to currently available antibiotics. All isolates were inhibited at concentrations less than or equal to 25 mug/ml, with the exception of 12% of isolates of Enterobacter spp. and 3% of isolates of Serratia marcescens. Its activity decreased with an increase in inoculum concentration of from 10(5) to 10(7) cells per ml.

Amoxicillin↗
PubMed1978

beta-lactamase insensitive or inhibitory beta-lactams: two approaches to the challenge of ampicillin-resistant E. coli.

The rising incidence of Gram-negative bacteria resistant to ampicillin in hospitals has brought about a need to develop novel beta-lactam antibiotics. This challenge is being met in two ways. First, attempts have been made to develop compounds insensitive to beta-lactamase hydrolysis. This has proved difficult in the penicillin series, but cefuroxime and cefoxitin are cephalosporin derivatives with the necessary properties. The second approach has been to discover novel beta-lactam nuclei capable of inhibiting beta-lactamases. So far this had led to the production of the clavulins and the olivacins, the latter class of molecules being closely related chemically to thienamycin.

Amidohydrolases↗
PubMed1979

Antibiotic susceptibility of anaerobic bacteria with special reference to Bacteroides fragilis.

It was shown that recent Swedish clinical isolates of anaerobic bacteria are susceptible to many antibiotics by the agar dilution method with the exception of the Bacteroides group versus beta-lactam antibiotics or tetracyclines. Strains of B. fragilis were inhibited by 4--greater than 128 micrograms benzylpenicillin or cephalothin/ml, 1.0--64 micrograms cefoxitin/ml, 0.064--2 micrograms clindamycin or metronidazole/ml, 2--8 micrograms chloramphenicol/ml, 2--16 micrograms fusidic acid/ml and 0.032--32 micrograms doxycycline/ml. Resistance to beta-lactam antibiotics was partly due to the production of beta-lactamase. Growth of beta-lactamase producing strains in the presence of enzyme inhibitors such as clavulanic acid or CP-45899 together with cephaloridine lowered the MIC's manyfold. Cefoxitin with relative resistance to beta-lactamases inhibited the majority of the strains at 8 micrograms/ml. Cefoxitin-resistant strains (MIC greater than or equal to 16 micrograms/ml) were also resistant to the new cephalosporins BL-S786 and HR-756 as well as to the new cefamycins A, B, CL619-183, CS-1170 and Sq-14359 and to thienamycin. Cefamycin CL619-183, only showed a slightly higher in vitro activity than cefoxitin. Resistance to the cefamycins could not be correlated to the production of beta-lactamases.

Anti-Bacterial Agents↗
PubMed2026

Burkholderia arboris bacteremia initially identified as Burkholderia cepacia complex: a genome-based case report.

We report a bloodstream Burkholderia arboris isolate from a 75-year-old man without cystic fibrosis. The organism was recovered from both aerobic bottles of two separately collected blood-culture sets and was initially assigned to the Burkholderia cepacia complex (Bcc) by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Whole-genome sequencing yielded three circular chromosomes and one circular plasmid. DFAST_QC identified B. arboris as the only type-strain match above the species threshold, with an average nucleotide identity of 99.48%; the next-highest match was B. seminalis at 93.33%. Multilocus sequence typing identified ST-2575, and ResFinder detected no acquired antimicrobial resistance genes. The patient improved after 14 days of meropenem therapy without recurrent B. arboris bacteremia. This report adds a clinically supported bloodstream infection, a complete genome resource, and detailed susceptibility data, while illustrating the importance of up-to-date reference genomes for species-level interpretation of unusual Bcc isolates.

Humans↗
PubMed2026

Evaluation of sequential phage-antibiotic therapy reveals enhanced biofilm control with meropenem and colistin in clinical MDR hypervirulent Klebsiella pneumoniae strain.

AIMS: The convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae (MDR-HvKp) has narrowed treatment options. Despite growing interest in phage-antibiotic synergy, this study evaluates the underexplored combinatorial effects of phage and antibiotics, including drug-specific interactions and sequence dependency, against the biofilm-forming MDR-HvKp clinical strain. METHODS AND RESULTS: A T5-like Klebsiella bacteriophage, Round, within the genus Webervirus, was therapeutically and genomically characterized. A biofilm-forming clinical strain, Kleb_134, was used to evaluate in vitro phage-antibiotic interactions with meropenem, colistin, and tigecycline in planktonic and biofilm models.In planktonic assays, phage combinations with meropenem and colistin resulted in a multi-log CFU reduction compared to monotherapies, whereas reduced efficacy was observed with tigecycline. In biofilm assays, pre-phage treatment followed by antibiotic exposure demonstrated the strongest biofilm reduction. Drug-specific and sequence-dependent effects were evident. Meropenem-phage combinations reduced biofilm biomass by 2.85-fold (high phage titre) and 3.8-fold (low phage titre), while colistin-phage combinations achieved reductions of 8.4-fold (high phage titre) and 2.8-fold (low phage titre). CONCLUSIONS: Sequential phage-antibiotic treatment was effective against MDR-HvKp biofilms, with pre-phage exposure enhancing antibiotic access through biofilm disruption. The bacteriostatic nature of tigecycline reduced efficacy by affecting phage replication. These findings highlight the importance of treatment sequence and antibiotic selection, and extend existing knowledge in optimizing therapeutic outcomes in MDR-HvKp infections.

Biofilms↗