Combinations Of Beta-lactam Antibiotics Research Articles

Tuberculosis and beta-lactam antibiotics.

Tuberculosis (TB) is one of the oldest health problems in the world and it remains unresolved. Multidrug-resistant-TB and extensively resistant-TB are a serious problem for control programs. The evaluation of available antibiotics has gained importance in recent years for the treatment of resistant TB. Beta-lactam antibiotics inhibit cell wall biosynthesis in the bacteria; the presence of beta-lactamase enzyme in TB bacilli raises the question of whether this group of antibiotics can be used in treatment. As a result, it has been reported that the combination of beta-lactam antibiotics with beta-lactamase is effective against Mycobacterium tuberculosis both in vitro and in vivo. The aim of this article is to review and discuss up-to-date knowledge and future perspective on beta-lactam antibiotics and TB.

Community-acquired pneumonia in adult HIV-infected patients: course, treatment, and prevention

This is a review of published data on community-acquired pneumonia (CAP) in adult HIV-infected patients. Morbidity of bacterial pneumonia in HIV-infected patients is 5- to 10-fold higher than that in general population. Wide use of antiretroviral therapy (ARVT) is associated with a reduction in morbidity of CAP in HIV-infected patients, but this reduction is not as significant as for other opportunistic infections. The most important risk factors for CAP are drug abuse, tobacco smoking, HIV-associated immunosuppression, hepatic cirrhosis, not to be treated with ARVT or ARVT withdrawal. Severe, complicated and invasive course of CAP and poor outcomes are seen more often in HIV-infected patients compared to general population. Bacterial pneumonia should be differed from pneumonia caused by Pneumocystis and from tuberculosis, especially in endemic countries and in patients with insidious onset of the disease. The standard therapy of CAP is applied in all patients independently of HIV status. However, administration of fluoroquinolones is restricted in regions with high prevalence of multi-drug resistant tuberculosis in HIV-infected patients before tuberculosis is excluded. Several studies have demonstrated that, in case of false initial diagnosis, 10-day monotherapy with a fluoroquinolone could form the resistance of Mycobacteria tuberculosis against this drug; this significantly complicates further treatment of tuberculosis and increases the treatment cost. Beta-lactams are not effective against tuberculosis; in 2016, WHO excluded macrolides from the list of medications for therapy of tuberculosis due to their low activity against M. tuberculosis. Therefore, empirical therapy of CAP in HIV-infected patients should be started with combination of beta-lactam antibiotic and newer macrolide. A strong protective effect of PPV23 vaccine against CAP was confirmed in HIV-infected patients, but the highest protective efficacy was seen in patients with relatively preserved immunity compared to patients with CD4 < 200 cells × µL -1 .

Synergistic Effect of Combined Antibiotics against Some Selected Multidrug Resistant Human Pathogenic Bacteria Isolated from Poultry Droppings in Akure, Nigeria

Antibiotic resistant bacteria pass between humans, between animals and between humans and animals in both directions, the use of antibiotics in poultry has contributed to multiple antibiotic resistant in pathogenic bacteria and use of two antibiotics might prevent the emergence of resistance to either. In this study, synergistic effect of combined antibiotics against multidrug resistant human pathogenic bacterial isolates from poultry droppings in Akure, Nigeria was examined. Collection of samples, isolation and identification of bacteria were carried out using standard microbiological method, antibiotic sensitivity test was performed by disc diffusion method and zone of inhibition was used to interpret the sensitivity test as resistant, susceptible or intermediate while combined effects of two antibiotics were investigated by macrobroth dilution and checkerboard assay methods while the synergetic effects of combined antibiotics were calculated using Fractional Inhibitory Concentration (FIC) and percentage synergistic interaction was calculated. All the ten (10) species of bacterial isolates were multidrug resistant and are less resistant to ofloxacin. The highest percentage synergistic interactions observed were Ofloxacin + Amoxicillin (90%), Ciprofloxacin + Amoxicillin (90%), Tetracycline + Amoxicillin (70%), Tetracycline + Augmentin (80%), Cotrimoxazol + Amoxicillin (50%), Cotrimoxazol + Augmentin (70%), Chloramphenicol + Amoxicillin (70%) and Chloramphenicol + Augmentin (80%). Poultry droppings is a potential source of human pathogenic bacteria, high frequency of multiple antibiotic resistance bacteria observed in this study is of great treat to man as this may cause the treatment of infection caused by these bacteria to be difficult. Combination of beta-lactam antibiotic with fluoroqunolones, tetracycline, Chloramphenicol and Cotrimoxazole was synergetic and this will reduce dose related toxicity and prevent resistance to single antibiotic.

Preventive Antibiotics for Infections in Acute Stroke

To provide a systematic overview and meta-analysis of randomized clinical trials evaluating preventive antibiotics in patients with acute stroke. The MEDLINE (1966-February 2009) and Cochrane databases and reference lists of retrieved articles. Randomized controlled trials on preventive antibiotic treatment in stroke. For inclusion, at least case fatality or infection rate had to be recorded. Each study was scored for methodological key issues and appraised by the Jadad scale. We extracted the data using a predetermined protocol and included all patients who were randomized or who started therapy in an intent-to-treat analysis. We identified 4 randomized clinical trials including 426 patients; 94% had ischemic stroke. Study interventions were fluoroquinolones in 2 and tetracycline or a combination of beta-lactam antibiotic with beta-lactamase inhibitor in 1. Therapy was started within 24 hours of stroke onset. Duration of therapy varied between 3 and 5 days. The methodological quality ranged from 2 to 5 on the Jadad scale, and studies were subject to potential bias. The proportion of patients with infection was significantly smaller in the antibiotic group than in the placebo/control group (32 of 136 [23.5%] vs 53 of 139 [38.1%] patients). The pooled odds ratio for infection was 0.44 (95% confidence interval, 0.23-0.86). Ten of 210 patients (4.8%) in the antibiotic group died, compared with 13 of 216 (6.0%) in the placebo/control group. The pooled odds ratio for mortality was 0.63 (95% confidence interval, 0.22-1.78). No major harm or toxicity was reported. In adults with acute stroke, preventive antibiotics reduced the risk of infection, but did not reduce mortality. The observed effect warrants evaluation of preventive antibiotics in large stroke trials.

Antagonism between penicillin and erythromycin against Streptococcus pneumoniae in vitro and in vivo

The combination of beta-lactam antibiotics and macrolides is often recommended for the initial empirical treatment of acute pneumonia in order to obtain activity against the most important pathogens. Theoretically, this combination may be inexpedient, as the bacteriostatic agent may antagonize the effect of the bactericidal agent. In this study, the possible interaction between penicillin and erythromycin was investigated in vitro and in vivo against four clinical isolates of Streptococcus pneumoniae with MICs of penicillin ranging from 0.016 to 0.5 mg/L and of erythromycin from 0. 25 to >128 mg/L. In vitro time-kill curves were generated with clinically relevant concentrations of penicillin (10 mg/L) and erythromycin (1 mg/L), either individually or in combination. Antagonism between penicillin and erythromycin was observed for the four isolates. In vivo interaction was investigated in the mouse peritonitis model. After intraperitoneal inoculation, penicillin and erythromycin were given either individually or in combination. For two of the four isolates, mortality was significantly higher in the groups treated with the combination of penicillin and erythromycin than in the groups treated with penicillin alone [32/36 (86%) vs. 3/12 (25%), P<0.05; and 24/36 (67%) vs. 3/12 (25%), P<0.05, respectively]. Using the mouse peritonitis model, in vivo time-kill curves showed that there was antagonism between erythromycin and penicillin for the examined isolate. The antagonism demonstrated in vitro and in vivo between penicillin and erythromycin suggests that ss-lactam antibiotics and macrolides should not be administered together unless pneumococcal infection is ruled out.

Endocarditis caused by Kingella denitrificans

We report the case of a 48-year-old man with native valve endocarditis caused by Kingella denitrificans. He was successfully treated with a combination of beta-lactam antibiotics and aminoglycosides, after which he underwent valve replacement surgery. This case represents the first report in the literature of elective native valve replacement. Previously reported cases are discussed together with management options, including suggestions for the treatment of patients with beta-lactam allergy and those infected with beta-lactamase producing strains.

Lysis of nongrowing Escherichia coli by combinations of beta-lactam antibiotics and inhibitors of ribosome function

It is generally assumed that only actively growing bacteria are killed by inhibitors of peptidoglycan synthesis. Several exceptional examples are described here. As expected, ampicillin did not lyse nongrowing, amino acid-deprived cultures of relA+ strains of Escherichia coli, but the subsequent addition of several ribosome inhibitors (chloramphenicol, tetracycline, gentamicin, and kanamycin) caused various degrees of lysis in such ampicillin-treated cultures. Of the antibiotics tested, only streptomycin was ineffective in this regard. Peptidoglycan synthesis has been shown to be inhibited in amino acid-deprived relA+ bacteria by the stringent control mechanism (E. E. Ishiguro and W. D. Ramey, J. Bacteriol. 127:1119-1126, 1976), and the ribosome inhibitors tested here relaxed peptidoglycan synthesis to various degrees under these conditions. The relative lysis-inducing activities of the ribosome inhibitors on ampicillin-treated, amino acid-deprived bacteria were directly correlated to their relative activities as stringent control antagonists. This phenomenon was not dependent on amino acid deprivation. Cultures treated with growth inhibitory levels of the various ribosome inhibitors alone were lysed by ampicillin, apparently because peptidoglycan synthesis continues uninhibited when growth is arrested by treatment with ribosome inhibitors. These results indicate that autolysis can be triggered by the inhibition of peptidoglycan synthesis occurring in the absence of wall expansion; i.e., active cell growth is unnecessary.

Management of infections caused by gram-negative bacilli: the role of antimicrobial combinations.

Treatment with antimicrobial combinations is generally used to provide broad-spectrum coverage and/or to enhance antimicrobial activity (synergism). Extensive in vitro documentation of synergism exists for many such combinations, but an obvious benefit has been difficult to demonstrate clinically. Several types of therapeutically useful combinations often result in synergism; these combinations include a cell wall-active agent with an aminoglycosidic aminocyclitol, a beta-lactamase inhibitor with a beta-lactam antibiotic, and agents that inhibit sequential steps in a metabolic pathway. Combinations of beta-lactam antibiotics may be synergistic by means of several mechanisms, but such combinations have significant potential for antagonism when used against gram-negative bacilli and, thus, must be evaluated closely before clinical use.

Amdinocillin pharmacokinetics: Simultaneous administration with cephalothin and cerebrospinal fluid penetration

In the treatment of serious infections, combinations of beta-lactam antibiotics are being utilized in order to avoid aminoglycoside toxicity and to achieve antibacterial synergy. The pharmacokinetic disposition of amdinocillin and cephalothin was determined, when administered alone or in combination to healthy volunteers, as well as the penetration of amdinocillin into human cerebrospinal fluid. Six subjects received, on separate occasions, single intravenous doses of amdinocillin 10 mg/kg, cephalothin 15 mg/kg, or a combination of the two in the same doses. The elimination half-lives of amdinocillin and cephalothin are increased when these drugs are given simultaneously, compared with when they are administered alone. However, no significant differences were observed. When they were given in combination, no significant changes in plasma clearance, renal clearance, or steady-state volume of distribution were found. Eight patients undergoing lumbar puncture for various neurologic disorders without inflamed meninges received a single dose of 10 mg/kg amdinocillin intravenously. One to two hours later, simultaneous plasma and cerebrospinal fluid samples were obtained. The concentration of amdinocillin in the cerebrospinal fluid ranged from approximately 1 to 10 percent of concomitant plasma concentrations. Thus, amdinocillin penetrates in the cerebrospinal fluid in marginal amounts in the absence of meningeal inflammation.