The Antimicrobial Implications of the Pharmacokinetics of Cotrimoxazole in CAPO Patients

1987 ◽  
Vol 7 (2) ◽  
pp. 74-77 ◽  
Author(s):  
Otegbola Ojo ◽  
Colina Jones ◽  
Donald L. Stevens

Cotrimoxazole (TMP/SMX) has been used to treat continuous ambulatory peritoneal dialysis (CAPD) associated peritonitis. It is considered bactericidal for some species. The most common single organism responsible for this type of peritonitis is Staph. epidermidis (SE). When the drug is given orally, the typical ratio of TMP to SMX achieved in the peritoneal fluid is 1:5, which is different from the optimal combination for antimicrobial synergy of 1:19. This study investigated the antimicrobial activity of TMP alone and TMP/SMX by agar dilution at ratios of 1:19, 1:10 and 1:5 against 99 strains of Staphylococcus epidermis (SE). The majority of strains were susceptible to TMP and to all ratios of TMP/SMX by the routine agar dilution methods. We studied the bactericidal activity of TMP/SMX against one strain each of SE and of Staph. aureus (SA) in pooled uninfected spent dialysate by killing curve experiments. TMP at concentrations of 0.5 to 2.0 μg/ml was bacteriostatic. TMP/SMX became slowly bactericidal when 5 % lysed horse blood, a source of thymidine phosphorylase, was added to the dialysate. It is concluded that susceptibility tests of inhibition do not predict bactericidal activity of TMP/SMX in recovered dialysate. Inhibition of TMP/ SMX is most likely due to thymidine present in dialysate. TMP alone was as effective against SE as TMP/ SMX. Until it is shown that bactericidal activity is not required for cure of CAPD-related peritonitis, cotrimoxazole should not be used routinely for its treatment.

2020 ◽  
Author(s):  
Lorena Isbej ◽  
Natacha Oyarzo ◽  
María José Contreras ◽  
Duniel Ortuño ◽  
Marusella Lam ◽  
...  

Abstract Background: The main goal of antimicrobials is to eliminate microorganisms that persists despite mechanical treatment. This is the case of Porphyromonas gingivalis (Pg), frequently isolated in patients with periodontitis. Global antibiotic studies evaluated in randomized clinical trials and in vitro studies have shown mixed results regarding effectiveness and susceptibility, even with different protocols where it is not clear if the laboratory test applied can affect the results. This information is relevant in order to obtain clinical outcomes and prevent antimicrobial resistance for their over-prescription or inadequate choice. The objective of this study was to describe the antimicrobial susceptibility in vitro of Pg to metronidazole, clindamycin, amoxicillin plus clavulanate, moxifloxacin and azithromycin in periodontal patients by three testing protocols.Methods: Microbiological samples were obtained in patients with a diagnosis of generalized moderate or severe periodontitis. They were incubated in anaerobic conditions for up to 7 days, and those morphologically compatible with Pg were isolated and identified by a mass spectrometer (MALDI-TOF MS). The three most frequently protocols for antimicrobials susceptibility tests (Blood agar- McFarland 0.5- Epsilometer test; Brucella blood agar- McFarland 1.0- Epsilometer test; Brucella blood agar- McFarland 0.5-Agar dilution) were applied to the same strain describing their profile and reporting any difference between the tests. The breakpoints considered the guidelines of CLSI and previous publications.Results: 50 patients (25 women, 25 men) with periodontitis between 34-69 years were selected. Finally, 25 Pg positives strains (50%) were recovered for the susceptibility analysis and all of them were highly sensitive to all antibiotics (range 96%-100%). Only one strain was resistant to azithromycin in one protocol, and no differences were found in the susceptibility results between the three tests.Conclusion: The Pg strains were highly susceptible to the five antibiotics evaluated in this population, showed a high level of susceptibility and significant agreement between the three tests applied, therefore the type of laboratory test used had not impacted on clinical interpretation. These findings are positives in terms of susceptibility and would provide several antibiotics treatment alternatives, and its prescription could be the best choice for the patient's specific context.


2010 ◽  
Vol 79 (1) ◽  
pp. 474-485 ◽  
Author(s):  
Robert C. Allen ◽  
Jackson T. Stephens

ABSTRACTMyeloperoxidase (MPO) is reported to selectively bind to bacteria. The present study provides direct evidence of MPO binding selectivity and tests the relationship of selective binding to selective killing. The microbicidal effectiveness of H2O2and of OCl−was compared to that of MPO plus H2O2. Synergistic microbicidal action was investigated by combiningStreptococcus sanguinis, a H2O2-producing microbe showing low MPO binding, with high-MPO-bindingEscherichia coli,Staphylococcus aureus, orPseudomonas aeruginosawithout exogenous H2O2, with and without MPO, and with and without erythrocytes (red blood cells [RBCs]). Selectivity of MPO microbicidal action was conventionally measured as the MPO MIC and minimal bactericidal concentration (MBC) for 82 bacteria includingE. coli,P. aeruginosa,S. aureus,Enterococcus faecalis,Streptococcus pyogenes,Streptococcus agalactiae, and viridans streptococci. Both H2O2and OCl−destroyed RBCs at submicrobicidal concentrations. Nanomolar concentrations of MPO increased H2O2microbicidal action 1,000-fold. Streptococci plus MPO produced potent synergistic microbicidal action against all microbes tested, and RBCs caused only a small decrease in potency without erythrocyte damage. MPO directly killed H2O2-producingS. pyogenesbut was ineffective against non-H2O2-producingE. faecalis. The MPO MICs and MBCs forE. coli,P. aeruginosa, andS. aureuswere significantly lower than those forE. faecalis.The streptococcal studies showed much higher MIC/MBC results, but such testing required lysed horse blood-supplemented medium, thus preventing valid comparison of these results to those for the other microbes.E. faecalisMPO binding is reportedly weak compared to binding ofE. coli,P. aeruginosa, andS. aureusbut strong compared to binding of streptococci. Selective MPO binding results in selective killing.


2000 ◽  
Vol 44 (3) ◽  
pp. 598-601 ◽  
Author(s):  
Ellie Hershberger ◽  
Michael J. Rybak

ABSTRACT We adapted an in vitro pharmacodynamic model of infection to incorporate infected fibrin clots. The bactericidal activities of various fluoroquinolones against two strains of penicillin-resistantStreptococcus pneumoniae were studied over a 48-h period. Bacteria were prepared in Muller-Hinton broth by using colonies from a 24-h tryptic soy agar plus 5% sheep blood plate and were added to a mixture of cryoprecipitate (80%) and thrombin (10%) to achieve approximately 106 CFU of organism per fibrin clot. The fibrin clots were suspended into the models and removed, in triplicate, at various time points over 48 h. Control models were also conducted to characterize the growth of S. pneumoniae in the growth medium without antibiotic. Trovafloxacin, gatifloxacin, clinafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin were administered to simulate their pharmacokinetic profiles in humans. Fibrin clot samples were also plated onto antibiotic-containing tryptic soy agar plus 5% lysed horse blood to detect resistance. The newer fluoroquinolones demonstrated better activity than ciprofloxacin against both isolates. In conclusion, the newer quinolones demonstrated significant activity against penicillin-resistant S. pneumoniae, with standard dosing resulting in area under the concentration-time curve/MIC ratios and peak concentration/MIC ratios that resulted in 99.9% killing against these isolates.


2018 ◽  
Author(s):  
SeungYun Han ◽  
HyunJung Kim ◽  
Jongchan Park ◽  
SangYun Lee ◽  
KyeoReh Lee ◽  
...  

Abstract:Antimicrobial susceptibility test (AST) is widely used to provide the minimum inhibitory concentration of bacteria, and crucial to provide appropriate uses of antibiotics and to address the issue of drug-resistance bacteria. However, ASTs require the time-consuming incubation about 16-20 h for the visual determination of the growth of bacterial colonies, which has been a major obstacle to on-site applications of ASTs. In this study, we propose a rapid and non-invasive method based on laser speckles to evaluate the bacterial growth movements in real time, thus reducing the time for the agar dilution method. With a simple configuration compatible with conventional agar plates, the analysis of laser speckle from samples enables the early detection of the presence of growth as well as its detailed history of the colony-forming movement on agar plates. Using the samples prepared through the same procedure as the agar dilution method, we obtained the AST results at least 4-8 hours earlier than the conventional method without compromising the accuracy. This technique does not require for the use of exogenous agents, but works for most bacteria regardless of their species. Furthermore, the distinctive responses of several species to microbial agents were revealed through the present technique supporting a comprehensive analysis of the effect of the antibiotics. The findings suggest that this new method could be a useful tool for rapid, simple, and low-cost ASTs in addition to providing the historical information of the bacterial growth on agar plates.


1998 ◽  
Vol 36 (2) ◽  
pp. 585-586
Author(s):  
Peter C. Fuchs ◽  
Arthur L. Barry ◽  
Steven D. Brown

A 10-laboratory collaborative effort was designed to generate data to propose quality control limits for susceptibility tests of trovafloxacin. Broth microdilution, agar dilution, and disk diffusion tests were evaluated with eight different control strains. All tests were reproducible, and control limits are proposed.


1998 ◽  
Vol 42 (4) ◽  
pp. 857-861 ◽  
Author(s):  
Dianne B. Hoellman ◽  
Melissa A. Visalli ◽  
Michael R. Jacobs ◽  
Peter C. Appelbaum

ABSTRACT The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, vancomycin, and teicoplanin were tested against 212 Enterococcus faecalis strains (9 β-lactamase producers) by standard agar dilution MIC testing (104 CFU/spot). The MICs at which 50 and 90% of the isolates were inhibited (MIC50s and MIC90s, respectively) were as follows (μg/ml): piperacillin, 4 and 8; piperacillin-tazobactam, 4 and 8; ticarcillin, 64 and 128; ticarcillin-clavulanate, 64 and 128; ampicillin, 2 and 2; ampicillin-sulbactam, 1 and 2; vancomycin, 1 and 4; and teicoplanin, 0.5 and 1. Agar dilution MIC testing of the nine β-lactamase-positive strains with an inoculum of 106 CFU/spot revealed higher β-lactam MICs (piperacillin, 64 to >256 μg/ml; ticarcillin, 128 to >256 μg/ml; and ampicillin, 16 to 128 μg/ml); however, MICs with the addition of inhibitors were similar to those obtained with the lower inoculum. Time-kill studies of 15 strains showed that piperacillin-tazobactam was bactericidal (99.9% killing) for 14 strains after 24 h at four times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Ampicillin gave 99.9% killing of 14 β-lactamase-negative strains after 24 h at eight times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Killing by ticarcillin-clavulanate was slower than that observed for piperacillin-tazobactam, relative to the MIC. For the one β-lactamase-producing strain tested by time-kill analysis with a higher inoculum, addition of the three inhibitors (including sulbactam) to each of the β-lactams resulted in bactericidal activity at 24 h at two times the MIC. For an enzyme-negative strain, addition of inhibitors did not influence kinetics. Kinetics of vancomycin and teicoplanin were significantly slower than those of the β-lactams, with bactericidal activity against 6 strains after 24 h at eight times the MIC, with 90% killing of 12 and 14 strains, respectively, at four times the MIC. Slower-kill kinetics by both glycopeptides were observed at earlier periods.


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