Effect Of Beta-lactam Antibiotics Research Articles

Acute kidney injury induced by beta-lactam antibiotics in children: A scoping review

Antibiotics are the agents that cause Acute Kidney Injuries (AKI) in children. A recent study has shown the incidence of nephrotoxicity by antibiotics reaches 16% in children. Beta-lactam types are not widely known for their nephrotoxic effect. This study aims to examine beta-lactam antibiotics' role in inducing children's renal failure. This search for a scoping review on the effect of beta-lactam antibiotics in children was carried out in December-January 2022-2023. We used some search engines with the year of publication 2012-2022 then extracted. The keyword combinations used are: “beta-lactams” OR “β-lactams” AND “acute renal failure” OR “acute renal injury” OR “nephrotoxic” OR “nephrotoxicity” AND “children” OR “pediatric” OR “neonate” NOT “adult”. Studies were excluded if the: (i) adult; (ii) were a review, systematic review, or meta-analysis; (iii) written in a language other than English; (iv) not available in full text; (v) have kidney disease before (vi) in vitro or in vivo. The article selection process was based on PRISMA-ScR. From 4032 articles that met the search criteria, 3 studies met the inclusion criteria. The result shows that beta-lactam increases the risk of acute renal injury in children. This review emphasizes the importance of choosing kidney-safe antibiotics for children.

АНАЛИЗ ДИНАМИКИ РАСПРОСТРАНЕННОСТИ ВОЗБУДИТЕЛЕЙ ИНФЕКЦИОННО-ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЙ ЧЕЛЮСТНО-ЛИЦЕВОЙ ОБЛАСТИ И ИЗМЕНЕНИЯ ИХ ЧУВСТВИТЕЛЬНОСТИ К АНТИБИОТИКАМ

To date, the issue of prevention and treatment of infectious and inflammatory diseases of the maxillofacial region is one of the leading unsolved problems among dental diseases. This pathology has a significant prevalence in the Republic of Belarus and in the world as a whole. The atypical clinical course of these diseases is observed with increasing frequency. There is a need for further study of the etiology and pathogenesis of inflammatory diseases of the maxillofacial region. The purpose of this study was to analyze the dynamics of pathogens prevalence of infectious and inflammatory diseases of the maxillofacial region and the changes in their sensitivity to antibiotics for 2001 and 2015-2020. The results of a bacteriological study of 1209 patients with infectious and inflammatory diseases of the maxillofacial region of odontogenic etiology undergoing inpatient treatment at the dental department of the Vitebsk Regional Clinical Hospital were analyzed. It has been found that over the last 19 years, a shift towards an increase in the number of methicillin-resistant isolates was revealed, which may indicate a decline in the effectiveness of beta-lactam antibiotics as starting empirical antibiotic therapy. The sensitivity of S.aureus and S.epidermidis isolates to cephalosporins, fluoroquinolones, lincosamides tends to decrease, the sensitivity of staphylococci to vancomycin and linezolid remains unchanged for the studied period. Streptococci have demonstrated an increase in their sensitivity to penicillins up to 100%, which indicates the rare use of these antibacterial drugs in dental hospitals. When comparing antibiotic resistance of Streptococcus spp. a tendency to the decreased sensitivity of isolates to cephalosporins of the third generation was revealed.

Влияние бета-лактамных антибиотиков на микроскопические параметры в Allium-тесте

The work examines the effect of beta-lactam antibiotics (cefotaxime, ampicillin, augmentin) on the pathology of mitosis in the Allium–test. Research methods: Allium–test, cytogenetic analysis, statistical analysis. It was established that the use of individual tested beta-lactam antibiotics increases the percentage of pathological mitoses in the cell by 1.8–3.3 times compared with the value in the control. With the combined use of cefotaxime and Augmentin, synergism appeared, as a result, the value of mitosis pathology turned out to be at the level of the number in the control; minimally represented pathologies indicating damage to the mitotic apparatus. It was revealed that all three beta-lactam antibiotics tested had a pronounced statmokinetic effect. At the same time, with the joint use of cefotaxime and Augmentin, k-mitosis was not registered in dividing cells. Comparison of the spectrum of pathological mitoses in the variants of the experiment showed that the pathology ‘chromosome runaway/backlog’ in anaphase of mitosis dominates in all variants. An increase in the concentration of Augmentin and ampicillin caused the suppression of pathological processes in onion meristematic cells, a decrease in PM values was observed. An increase in Augmentin concentration does not affect the composition and spectrum of pathological mitoses; ampicillin has a decrease in the level of most of the recorded pathologies of mitosis.

Imipenem-associated seizure in a patient operated for left-sided colon tumor /Sol kolon tumoru nedeniyle opere edilen hastada imipenem iliskili nobet

Although the pathophysiology of drug-associated seizures involves many factors, it mainly depends on the culprit drug and case-specific factors. There is usually no previous history of epilepsy in these patients, and epileptic seizures are due to lowering in epileptic threshold by the culprit drug. Epileptic seizures usually do not recur when the culprit agent is discontinued. Convulsion is a rare side effect of beta-lactam antibiotics. The neurotoxic side effects of carbapenem group antibiotics are thought to occur through an interaction with amino butyric acid receptors. Meropenem and imipenem are also a carbapenem group antibiotic. A 61-year-old man who developed a postoperative wound infection after being operated for left colon tumor had Klebsiella Pneumoniae proliferation in culture antibiogram and was put on imipenem/cilastatin treatment. He developed seizures with tonic-clonic convulsions on the fourth day of treatment, and the seizures were attributed to the imipenem/cilastatin treatment. No other pathology suggestive of seizure etiology could be found in his examinations. His antibiotic regimen was changed to a different one and he was discharged in good health on the 11th day of his hospital admission.

Epidemiological investigation of "beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR)"

Mu3 strain with heterogeneous intermediated-resistance to vancomycin (hetero-VISA) reported in 1997, also have possessed a character of an antagonistic effect of beta-lactam antibiotics and vancomycin. Mu3 is only strain which satisfies the definition of hetero-VISA in Japan. But, MRSA with antagonistic effects of beta-lactam antibiotics and vancomycin, was reported by many institutions. To separate hetero-VISA, we called "beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR)". But the detection rate of clinical isolated BIVR in Japan is unknown, we reported on the detection method and the epidemiological investigation for BIVR. Mu 3 agar containing 4 micrograms/mL of vancomycin is used to detect BIVR. Mu3 strains were spread on the agar, BIVR can grow around the paper disc impregnated with ceftizoxime or grow on the whole surface on Mu 3 agar after incubation. The detection rate of BIVR was 45 in 717 (6.3%) clinical isolated strains. In detected strains as BIVR, the number of strains with grown on the whole surface of Mu3 agar showing a high resistance to vancomycin were 10 strains (1.4%). Besides, from 106 strains of blood isolates MRSA, BIVR were detected 16 strains (15.1%), from 611 strains of non-blood isolates MRSA, BIVR were detected 29 strains (4.7%) (P < 0.0001). In BIVR strains grown on the whole surface of Mu3 agar, the number of BIVR strains isolated from blood were 8 in 106 (7.5%), from non-blood were 2 in 611 (0.3%) (P < 0.0001). On one side, hetero-VISA were not detected from all of BIVR growing on the whole surface of Mu3 agar. As a result, detection method and the definition of BIVR were quite different from those of hetero-VISA. An existence of BIVR in Japan was confirmed, we thought that the high detection rate of BIVR isolated from blood compared with that of non-blood showed the pathogenecity of BIVR which contribute to MRSA infections.

The mechanism of resistance of Pseudomonas aeruginosa to beta-lactam antibiotics and clinical significance.

To study the resistant mechanism and clinical significance of pseudomonas aeruginosa to beta-lactam antibiotics, the outer membrane permeability rate of 30 P. aeruginosa strains to 5 beta-lactam antibiotics was measured and their production of beta-lactamase and the beta-lactamase genes they carried detected. Furthermore, the relationship between the permeability, beta-lactamase and the clinical effects of beta-lactam antibiotics was observed. By using 14C-penicillin and liquid-scintillant isotope assay, the affinity of penicillin binding proteins (PBPS) was measured and their roles in the resistant mechanism studied. It was revealed that the permeability rate was higher in sensitive strains than in resistant ones (P < 0.05). All strains harbored 1-4 beta-lactamase genes and produced beta-lactamase. Higher permeability rate and higher degree of stability to beta-lactamase indicated better clinical therapeutic effects. The affinity of PBPs changed little without regard to the permeability and beta-lactamase. These results suggested that the permeability of outer membrane and beta-lactamase, but not PBPs, played important roles in the resistant mechanism of P. aeruginosa to beta-lactam antibiotics and affected the clinical therapeutic effectiveness of some patients.

Dual mechanisms of GABAa response inhibition by β‐lactam antibiotics in the pyramidal neurones of the rat cerebral cortex

1. The effects of beta-lactam antibiotics on the gamma-aminobutyric acid (GABA)-induced Cl- current were investigated in pyramidal neurones freshly dissociated from the rat frontal cortex by the use of a nystatin-perforated patch recording mode under voltage-clamp conditions. 2. The GABA-induced inward current increased in a concentration-dependent manner with an EC50 of 6.7 x 10(-6) M at a holding potential of -40 mV. The GABA response was accompanied by an increase in the membrane conductance and reversed at near the Cl- equilibrium potential. 3. All beta-lactams (penicillin, imipenem, aztreonam and cefotiam) inhibited the 10(-5) M GABA-induced response in a concentration-dependent manner with an IC50 and Hill coefficient of 1.3 x 10(-3) M and 0.64 for penicillin, 9.6 x 10(-4) M and 0.83 for imipenem, 2.5 x 10(-3) M and 9.99 for aztreonam, and 2.9 x 10(-4) M and 1.03 for cefotiam. 4. Imipenem inhibited the GABA-response competitively while penicillin inhibited the same response in a noncompetitive fashion. 5. The inhibitory action of imipenem showed no voltage-dependency, whereas the effect of penicillin was voltage-dependent. 6. It is thus proposed that some classes of beta-lactams, including imipenem may have a mechanism that is different from penicillin and competitively affects the GABAA receptor.

Antibiotic-induced release of endotoxin: a reappraisal.

A three- to 20-fold increase in the total concentration of endotoxin occurs as a consequence of antibiotic action on gram-negative bacteria both in vitro and in vivo. There is considerable overlap between the effect of beta-lactam antibiotics and non-beta-lactam antibiotics. Moreover, there is an unexplained delay between the lethal activity of antibiotics and the release of endotoxin. Hence, the mechanism whereby antibiotic action leads to the release of endotoxin is unclear, and mechanisms other than bacterial lysis warrant consideration. The evidence that the release of endotoxin has clinical importance is conflicting, and the issue is unresolved. However, nonlytic release may have implications for the therapeutic efficacy of antiendotoxin immunotherapy. Although frequently cited in the context of the antibiotic-induced release of endotoxin, a number of important differences pertain to conditions, such as the Jarisch-Herxheimer reaction and the tumor lysis syndrome, for which there is clear evidence of an initial deterioration with effective therapy.

In Vitro Susceptibility vs. In Vivo Efficacy of Various Antimicrobial Agents against the Bacteroides fragilis Group

In vitro susceptibility testing is only one step in the evaluation of the potential efficacy of antimicrobial agents against the Bacteroides fragilis group. An assessment of in vivo efficacy, with a consideration of the factors that can best be studied in an infected host, is also an integral part of this process. Abscess models in rodents have been used to correlate in vitro activity with in vivo efficacy against this group of microorganisms. For metronidazole, clindamycin, moxalactam, and cefoxitin, the correlation was strong; for chloramphenicol and carbenicillin, it was not. In vivo studies of mixed infection with the B. fragilis group and Escherichia coli showed that cefoxitin and imipenem were effective; in contrast, cefotetan was not effective against resistant strains. Only strains susceptible to ceftizoxime in the agar dilution test were also affected by this drug in vivo. The so-called inoculum effect noted with ceftizoxime may explain this finding. In vivo elimination of encapsulated organisms of the B. fragilis group was found to be more difficult than elimination of unencapsulated isolates. The beta-lactamase produced by Bacteroides species can protect the enzyme-producing organism as well as its partners in mixed infections from the effects of beta-lactam antibiotics. These data illustrate the complexity and difficulties encountered when in vitro activity is correlated with in vivo efficacy.

A prospective study of neutropenia induced by high doses of β-lactam antibiotics

A prospective study on the effect of beta-lactam antibiotics on granulopoiesis was carried out in 29 consecutive patients with bacterial endocarditis. Fourteen patients received a high dose of benzylpenicillin, up to 18 g/day, but in only three of them could the treatment be fulfilled as planned, for a mean time of 25 days. In 11 benzylpenicillin treated patients treatment had to be discontinued because of fever, rash or neutropenia. Neutropenia appeared in seven patients after 14-24 (mean 22) days. No superinfection occurred during the neutropenic phase which lasted 2-12 days. Patients with neutropenia differed significantly from others in having a lowered pretreatment neutrophil count (3.2 vs 10.4). In 15 patients treated with other beta-lactams, three cases of fever and rash and one case of neutropenia were seen in patients treated with cloxacillin 12 g daily. It was concluded that a daily dose of 18 g of benzylpenicillin is too high for longer treatment periods and that patients with initial low counts of neutrophils have an increased risk of developing neutropenia.

Vitamin K-reversible hypoprothrombinemia in rats. I. Sex differences in the development of hypoprothrombinemia and the effects of beta-lactam antibiotics.

Male and female rats were fed an ordinary diet which contained about 500 ng vitamin K/g or a vitamin K-deficient diet containing less than 5 ng vitamin K/g. Hypoprothrombinemic changes such as prolongation of the prothrombin time (PT) and activated partial thromboplastin time (APTT) were detected in male rats within 4-6 days after feeding of the vitamin K deficient diet. Blood clotting factor VII and descarboxy prothrombin (PIVKA) levels changed rapidly, with maximum alteration at 2-4 days. Similar changes in factor VII and PIVKA levels were observed in female rats, but they appeared only after feeding of the K deficient diet for a long period. PT and APTT in female rats showed slight or no alteration even after 10 day feeding of the K-deficient diet. These results indicate that male rats are more susceptible to vitamin K deficiency than female rats. Administration of latamoxef led to a dose-dependent development of hypoprothrombinemia in vitamin K-deficient female rats. The hypoprothrombinemia in vitamin K-deficient female rats was caused by beta-lactam antibiotics with N-methyltetrazolethiol, thiadiazolethiol and methyl-thiadiazolethiol as the 3'-position substituent of the cephem nucleus.

Effects of beta-lactam antibiotics on the acetaldehyde-metabolizing system in germ-free rats.

Effects of several beta-lactam antibiotics on the acetaldehyde-metabolizing system were studied using germ-free rats. Administration of cefamandole (CMD) to the rats caused a decrease in liver mitochondrial low Km aldehyde dehydrogenase activity and an increase in blood acetaldehyde level during ethanol metabolism, similar to the case in conventional rats. Oral administration of CMD produced a pronounced increase in blood acetaldehyde level compared to the subcutaneous administration of the antibiotic. When the animals were given various beta-lactam antibiotics subcutaneously, only the antibiotics having an N-methyltetrazolylthiomethyl group at the 3-position of the cephalosporin nucleus exhibited the disulfiram-like effects on the acetaldehyde-metabolizing system. The results indicate that intestinal bacteria do no participate in the development of the disulfiram-like reaction of several beta-lactam antibiotics.

Effect of beta-lactam antibiotics on a human myeloid cell line: investigation of potential in vivo correlates in the mouse.

Effect of beta-lactam antibiotics on a human myeloid cell line: investigation of potential in vivo correlates in the mouse.

Effects of beta-lactam antibiotics on eukaryotic cells.

A symposium on effects of beta-lactam antibiotics on eukaryotic cells was held as part of the 9th International Congress of Infectious and Parasitic Diseases (Munich, Germany, July 1986). This symposium provided an opportunity to review recent work on the effect of beta-lactam structures on mammalian cells in culture and to speculate on possible clinical implications. This paper is a comment on the subject matter covered by the symposium papers which follow.

Interaction of beta-lactam antibiotics with the bactericidal activity of leukocytes against Escherichia coli.

The effect of beta-lactam antibiotics on phagocytosis and intracellular killing of four isogenic Escherichia coli strains differing in their 0- and K antigens was studied by adopting the rat polyvinyl-sponge model. The penicillins mezlocillin, ticarcillin and piperacillin rendered all four isogenic E. coli strains more susceptible to intraleukocyte killing; the cefalosporins tested exhibited inhomogenous effects; lamoxactam was marginally effective, whereas cefoxitin was completely ineffective; cefotaxime caused an increase in intracellular killing of the capsule-defective mutant only. The beta-lactam promoted increase in intracellular killing could be inhibited by alpha-methylmannoside but not by alpha-methylglucoside. Free-flow electrophoretic separation of mezlocillin-treated bacteria and guinea pig erythrocytes revealed that co-migration of E. coli and erythrocytes respectively could be inhibited by alpha-methylmannoside but not by alpha-methylglucoside. These data indicate that mezlocillin interferes with the mannose sensitive adhesins of E. coli.

Effect of beta-lactam antibiotics on migration and bactericidal activity of human phagocytes.

The effect of beta-lactam antibiotics upon some functions of human phagocytes was examined. Penicillins (carbenicillin and piperacillin), thienamycin, and cephalosporins (cefotetan, ceftazidime, and moxalactam) had no effect on either the random or directional migration or on the bactericidal activity of neutrophils and monocytes against Staphylococcus aureus. On the contrary, cefoperazone at therapeutic levels was shown to inhibit neutrophil chemotaxis.

Effects of beta-lactam antibiotics on peptidoglycan synthesis in growing Neisseria gonorrhoeae, including changes in the degree of O-acetylation.

Low concentrations of beta-lactam antibiotics caused an increased uptake of radioactive glucosamine into the sodium dodecyl sulfate-insoluble peptidoglycan of growing Neisseria gonorrhoeae. There was no appreciable change in the (small) amount of sodium dodecyl sulfate-soluble polymer present in the cultures. The sodium dodecyl sulfate-insoluble product in control cells was only partially dissolved by egg-white lysozyme (about 40%), but could all be released by the Chalaropsis B muramidase. In cells exposed to beta-lactams the proportion of labeled peptidoglycan susceptible to lysozyme increased to 60%. Examination of the Chalaropsis B digests by thin-layer chromatography showed that they contained disaccharide-peptide monomers with and without O-acetylation and bis-disaccharide-peptide dimers with one or two O-acetyl groups, or with none. beta-Lactam antibiotics caused a decrease in the degree of O-acetylation but did not greatly affect the amount of peptidoglycan cross-linking. They also had the effect of enlarging the bacteria and conserving and thickening the septa that could be observed in thin sections under the electron microscope. The relationship between these results and the effects of beta-lactams on in vitro synthesis of peptidoglycan by ether-treated N. gonorrhoeae is discussed.

Effect of beta-lactam antibiotics on bacterial cell growth rate.

The effect of penicillins and cephalosporins on the rate of growth of individual cells of Escherichia coli on agar was determined by measurement of cell length using photomicrographs taken at frequent intervals. When exposed to cephalexin or carbenicillin at twice the minimum inhibitory concentration cell division was inhibited but growth in length proceeded at a uniform exponential rate until abruptly terminated by lysis. The rate of growth of such filamentous cells did not differ significantly from that of normal cells grown in the absence of antibiotic. In contrast, exposure to cephaloridine and amoxycillin at twice the minimum inhibitory concentration resulted in a marked diminution in the rate of cell growth, and lysis occurred very much sooner. At concentrations greatly in excess of the minimum inhibitory concentration (greater than 100-fold) cephalexin also resulted in a diminution in the rate of cell growth and this was accompanied by earlier lysis. The significance of these findings is discussed in relation to the mode of action of beta-lactam antibiotics.

In vitro studies on bacterial colonization. The effects of beta-lactam antibiotics on the growth of Escherichia coli and Pseudomonas aeruginosa in mixed culture.

Many cases of Pseudomonas aeruginosa infection are considered to be secondary superinfections, resulting from bacterial colonization. Such cases of superinfection with P. aeruginosa developing after administration of cephalosporin or penicillin are offering serious clinical problems. To make a fundamental analysis of the development of such superinfections, attempts were made to compare the growth patterns of Escherichia coli and P. aeruginosa in pure and mixed cultures and to determine the effects of cephalothin, cefazolin, cephalexin, and ampicillin on the growth patterns. In mixed cultures, the growth of P. aeruginosa was markedly inhibited by E. coli. The higher the concentration of each of the cephalosporins and ampicillin added to the mixed culture, the smaller the population of E. coli sensitive to these agents. When the population of E. coli became smaller than that of P. aeruginosa, which is resistant to these agents, the latter was restored to the same population level as that in pure cultures. Experimental bacterial colonization, by which the predominant population of E. coli was replaced by that of P. aeruginosa in mixed culture, was brought about more efficiently with the cephalosporins than with ampicillin. This might be accounted for by the difference in minimal inhibitory concentration for P. aeruginosa between ampicillin and the other three agents.

Suppression of lytic effect of beta lactams on Escherichia coli and other bacteria.

Growth of E. coli at pH 5 protected the bacteria against the lytic effect of beta lactam antibiotics typically observed when the cells are grown at pH 7 or 7.5, i.e., the pH values routinely used in laboratory experiments. In contrast, the typical effects of beta lactam antibiotics on cellular shape and elongation and cell division appeared to be similar in cultures grown under neutral and acid pH conditions. The pH-dependent antibiotic tolerance can also be demonstrated with pneumococci, staphylococci, streptococci, and Bacillus subtilis. We suggest that the mechanism of the pH-dependent antibiotic tolerance may involve either the production of a more stable plasma membrane or the suppression of the activity of a murein hydrolase(s) that catalyzes the antibiotic-induced lysis; at least a fraction of these enzyme molecules may be localized at the cell surface and be accessible to experimental manipulation.