scholarly journals Pharmacodynamic properties of BAY 12-8039 on gram-positive and gram-negative organisms as demonstrated by studies of time-kill kinetics and postantibiotic effect.

1997 ◽  
Vol 41 (6) ◽  
pp. 1377-1379 ◽  
Author(s):  
F J Boswell ◽  
J M Andrews ◽  
R Wise
Keyword(s):  
Streptococcus Pyogenes ◽  
Coli Strain ◽  
Postantibiotic Effect ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Marked Activity ◽  
Gram Negative Organisms ◽  
Time Kill ◽  
Kinetics Of

Time-kill kinetics of BAY 12-8039 were studied at two inocula against three strains each of Bacteroides fragilis, Escherichia coli, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The postantibiotic effects of BAY 12-8039 were studied on three strains each of E. coli, S. aureus, H. influenzae, Streptococcus pyogenes, and Streptococcus pneumoniae. The pharmacodynamic data demonstrated that BAY 12-8039 has marked activity against gram-positive and gram-negative organisms (under both anaerobic and aerobic conditions) and anaerobes. BAY 12-8039 also exhibited a postantibiotic effect of >1 h for all strains except one E. coli strain.

scholarly journals Gepotidacin (GSK2140944) In Vitro Activity against Gram-Positive and Gram-Negative Bacteria

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
R. K. Flamm ◽  
D. J. Farrell ◽  
P. R. Rhomberg ◽  
N. E. Scangarella-Oman ◽  
H. S. Sader
Keyword(s):  
Postantibiotic Effect ◽  
Gram Positive ◽  
Bacterial Dna ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Time Kill ◽  
Synergy Testing ◽  
Potential Use

ABSTRACT Gepotidacin is a first-in-class, novel triazaacenaphthylene antibiotic that inhibits bacterial DNA replication and has in vitro activity against susceptible and drug-resistant pathogens. Reference in vitro methods were used to investigate the MICs and minimum bactericidal concentrations (MBCs) of gepotidacin and comparator agents for Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli. Gepotidacin in vitro activity was also evaluated by using time-kill kinetics and broth microdilution checkerboard methods for synergy testing and for postantibiotic and subinhibitory effects. The MIC90 of gepotidacin for 50 S. aureus (including methicillin-resistant S. aureus [MRSA]) and 50 S. pneumoniae (including penicillin-nonsusceptible) isolates was 0.5 μg/ml, and for E. coli (n = 25 isolates), it was 4 μg/ml. Gepotidacin was bactericidal against S. aureus, S. pneumoniae, and E. coli, with MBC/MIC ratios of ≤4 against 98, 98, and 88% of the isolates tested, respectively. Time-kill curves indicated that the bactericidal activity of gepotidacin was observed at 4× or 10× MIC at 24 h for all of the isolates. S. aureus regrowth was observed in the presence of gepotidacin, and the resulting gepotidacin MICs were 2- to 128-fold higher than the baseline gepotidacin MICs. Checkerboard analysis of gepotidacin combined with other antimicrobials demonstrated no occurrences of antagonism with agents from multiple antimicrobial classes. The most common interaction when testing gepotidacin was indifference (fractional inhibitory concentration index of >0.5 to ≤4; 82.7% for Gram-positive isolates and 82.6% for Gram-negative isolates). The postantibiotic effect (PAE) of gepotidacin was short when it was tested against S. aureus (≤0.6 h against MRSA and MSSA), and the PAE–sub-MIC effect (SME) was extended (>8 h; three isolates at 0.5× MIC). The PAE of levofloxacin was modest (0.0 to 2.4 h), and the PAE-SME observed varied from 1.2 to >9 h at 0.5× MIC. These in vitro data indicate that gepotidacin is a bactericidal agent that exhibits a modest PAE and an extended PAE-SME against Gram-positive and -negative bacteria and merits further study for potential use in treating infections caused by these pathogens.

P1173PERITONEAL DIALYSIS INFECTIONS IN MALTA - TRENDS OVER ELEVEN YEARS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Angela Borg Cauchi ◽  
Maria Angela Gauci ◽  
Theresia Dalli ◽  
James Gauci ◽  
James Farrugia ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Coagulase Negative Staphylococcus ◽  
Distributed Data ◽  
Dialysis Modality ◽  
Gram Positive ◽  
Gram Negative ◽  
Male Predominance ◽  
E Coli ◽  
Number Of Patients ◽  
Gram Negative Organisms

Abstract Background and Aims Infections related to peritoneal dialysis (PD) are still a cause of morbidity and mortality. We describe an overview of PD peritonitis and catheter-related infections (CRI) in Malta over a period of eleven years. We also describe trends in dialysis modality over the years. Method All patients undergoing PD in Malta during 2008 and 2018 were analysed. Data from 2008-2012 was retrospective, shown as mean, that from 2013-2018 prospective. International Society for Peritoneal Dialysis (ISPD) definitions were used. Results for categorical responses were summarized using absolute numbers and percentages. Medians (range) were used to describe continuous non-normally distributed data. Results The total number of patients undergoing PD from 2008 till 2018 were 137 (2008-2012), 91, 80, 126, 117, 102, 103 respectively. There was an overall male predominance of 63.5% (61-67). Patient years at risk were 85.80, 85.25, 89.71, 83.70, 79.69, 72.88 since 2013 respectively. The overall incidence of diabetes mellitus was 45.3% (41.8-50), cardiovascular disease 34.2% (33.8-35), hypertension 79.3% (73.8-84.6). PD was used in 50% of dialysis modality prior to 2012, 39% in 2018. Initially 51% used Automated PD (APD), with 21% assisted PD, in 2018 39% used APD, with 6% assisted PD. PD peritonitis rates from 2008 were 0.38, 0.31, 0.35, 0.46, 0.43, 0.57, 0.54, 0.43, 0.39, 0.40, 0.46 episodes/patient year respectively There was marked dominance of Gram-positive peritonitis, mainly Staphylococcal, with a reduction of coagulase-negative-Staphylococcus from 0.26 episodes/patient in 2013 to 0.03 in 2017, 0.11 in 2018. Methicillin-resistant S. aureus (MRSA) peritonitis decreased from 0.03 episodes/patient to nil in 2016, 2017, 0.01 episodes/patient in 2018. Amongst Gram-negative peritonitis, Pseudomonas rates decreased from 0.06 to 0.03 episodes/patient in 2018, nil in 2016. Escherichia coli rates decreased from 0.02 episodes/patient to nil in the last three years. Fungal rates from 0.03 to 0.01 episodes/patient/year, with nil in 2016, 2017. Catheter-related infection rates were 0.39 (2008-2012), 0.35, 0.91, 0.37, 0.38, 0.25, 0.50 episodes/patient/year respectively. There was a higher incidence of recurrent infections in 2014, none in 2015 and 2016. Gram-negative organisms accounted for 57% of all CRI, predominantly Pseudomonas at 0.12 (2008-2012), 0.06, 0.09, 0.09, 0.14, 0.03, 017 episodes/patient/year respectively. Gram-positive CRI were mostly Staphylococcus aureus, peaking in 2014 at 0.38 episodes/patient/year. MRSA rates declined from 0.15 to 0.01 episodes/patient/year in 2018. Conclusion PD peritonitis rates in Malta between 2008 and 2018 were below the ISPD recommended threshold. There were no episodes of MRSA in 2016, 2017, no Pseudomonas in 2016, no E coli in the last three years and no fungal PD peritonitis in 2016, 2017. CRI rates also declined, with an overall predominance of Gram-negative infections.

Activity of Telithromycin (HMR 3647) against Anaerobic Bacteria Compared to Those of Eight Other Agents by Time-Kill Methodology

1999 ◽  
Vol 43 (8) ◽  
pp. 2027-2031 ◽  
Author(s):  
Kim L. Credito ◽  
Lois M. Ednie ◽  
Michael R. Jacobs ◽  
Peter C. Appelbaum
Keyword(s):  
Propionibacterium Acnes ◽  
Anaerobic Bacteria ◽  
Bacteroides Fragilis ◽  
Bacteroides Thetaiotaomicron ◽  
Gram Positive ◽  
Gram Negative ◽  
Amoxicillin Clavulanate ◽  
Erythromycin A ◽  
Time Kill ◽  
Kinetics Of

ABSTRACT Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition of Oxyrase in order to prevent the introduction of CO2. Macrolide-azalide-ketolide MICs were 0.004 to 32.0 μg/ml. Of the latter group, telithromycin had the lowest MICs, especially against non-Bacteroides fragilis group strains, followed by azithromycin, clarithromycin, erythromycin A, and roxithromycin. Clindamycin was active (MIC ≤ 2.0 μg/ml) against all anaerobes except Peptostreptococcus magnus and Bacteroides thetaiotaomicron, while pristinamycin MICs were 0.06 to 4.0 μg/ml. Amoxicillin-clavulanate had MICs of ≤1.0 μg/ml, while metronidazole was active (MICs, 0.03 to 2.0 μg/ml) against all exceptPropionibacterium acnes. After 48 h at twice the MIC, telithromycin was bactericidal (≥99.9% killing) against 6 strains, with 99% killing of 9 strains and 90% killing of 10 strains. After 24 h at twice the MIC, 90, 99, and 99.9% killing of nine, six, and three strains, respectively, occurred. Lower rates of killing were seen at earlier times. Similar kill kinetics relative to the MIC were seen with other macrolides. After 48 h at the MIC, clindamycin was bactericidal against 8 strains, with 99 and 90% killing of 9 and 10 strains, respectively. After 24 h, 90% killing of 10 strains occurred at the MIC. The kinetics of clindamycin were similar to those of pristinamycin. After 48 h at the MIC, amoxicillin-clavulanate showed 99.9% killing of seven strains, with 99% killing of eight strains and 90% killing of nine strains. At four times the MIC, metronidazole was bactericidal against 8 of 10 strains tested after 48 h and against all 10 strains after 24 h; after 12 h, 99% killing of all 10 strains occurred.

scholarly journals What an Escherichia coli Mutant Can Teach Us About the Antibacterial Effect of Chlorophyllin

2019 ◽  
Vol 7 (2) ◽  
pp. 59 ◽  
Author(s):  
Marcus Krüger ◽  
Peter Richter ◽  
Sebastian Strauch ◽  
Adeel Nasir ◽  
Andreas Burkovski ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Outer Membrane ◽  
High Sensitivity ◽  
Coli Strain ◽  
Photodynamic Treatment ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Gram Positive Bacteria ◽  
Bacterial Model

Due to the increasing development of antibiotic resistances in recent years, scientists search intensely for new methods to control bacteria. Photodynamic treatment with porphyrins such as chlorophyll derivatives is one of the most promising methods to handle bacterial infestation, but their use is dependent on illumination and they seem to be more effective against Gram-positive bacteria than against Gram-negatives. In this study, we tested chlorophyllin against three bacterial model strains, the Gram-positive Bacillus subtilis 168, the Gram-negative Escherichia coli DH5α and E. coli strain NR698 which has a deficient outer membrane, simulating a Gram-negative “without” its outer membrane. Illuminated with a standardized light intensity of 12 mW/cm2, B. subtilis showed high sensitivity already at low chlorophyllin concentrations (≤105 cfu/mL: ≤0.1 mg/L, 106–108 cfu/mL: 0.5 mg/L), whereas E. coli DH5α was less sensitive (≤105 cfu/mL: 2.5 mg/L, 106 cfu/mL: 5 mg/L, 107–108 cfu/mL: ineffective at ≤25 mg/L chlorophyllin). E. coli NR698 was almost as sensitive as B. subtilis against chlorophyllin, pointing out that the outer membrane plays a significant role in protection against photodynamic chlorophyllin impacts. Interestingly, E. coli NR698 and B. subtilis can also be inactivated by chlorophyllin in darkness, indicating a second, light-independent mode of action. Thus, chlorophyllin seems to be more than a photosensitizer, and a promising substance for the control of bacteria, which deserves further investigation.

Pivmecillinam in the Treatment of Childhood Pyelonephritis

1983 ◽  
Vol 11 (2) ◽  
pp. 113-115 ◽  
Author(s):  
Ingemar Helin
Keyword(s):  
Urinary Tract Infection ◽  
Body Weight ◽  
Urinary Tract ◽  
Upper Urinary Tract ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Gram Negative Organisms ◽  
A Prospective Study ◽  
Klebsiella Spp

In a prospective study, twenty children with a mean age of 4 years were treated with pivmecillinam, 25 mg to 40 mg per kilogram body-weight and day, for acute pyelonephritis. Urine cultures yielded growth of E. coli in sixteen instances, Klebsiella spp. in two, S. saprophyticus in one and a mixed Gram-positive flora in one patient. All children fulfilled the diagnostic criteria for upper urinary tract infection. In all cases where Gram-negative pathogens were responsible, the infections were eradicated. One reinfection was registered in a child with a concomitantly discovered congenital urological malformation. Pivmecillinam also cured one patient infected with S. saprophyticus but was ineffective in the case of mixed Gram-positive flora. It is concluded that pivmecillinam is a valuable new drug for the management of pyelonephritis in children, as most of these infections are caused by Gram-negative organisms.

scholarly journals In-vitro activity of tigecycline and comparator agents against common pathogens: Indian experience

2019 ◽  
Vol 13 (03) ◽  
pp. 245-250 ◽  
Author(s):  
Balaji Veeraraghavan ◽  
Aruna Poojary ◽  
Chaitra Shankar ◽  
Anurag Kumar Bari ◽  
Seema Kukreja ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Test Study ◽  
Gram Negative Organisms ◽  
Potential Reserve ◽  
Klebsiella Spp

Introduction: Tigecycline Evaluation and Surveillance Trail (TEST) study is an on-going global surveillance. The study was performed to determine the susceptibility of common pathogens to tigecycline and comparator antibiotics by broth microdilution (BMD) at two tertiary care centres in India from 2015 to 2017. Methodology: Total of 989 isolates collected from various clinical specimens between January 2015 and September 2017 from two centres in India were included. BMD was performed to determine the minimum inhibitory concentration (MIC) for tigecycline and comparator antibiotics. Results: Among Gram-negative bacteria, susceptibility to tigecycline was lowest among Klebsiella spp. being 84% while others such as E. coli, Enterobacter spp., Serratia spp. and H. influenzae showed susceptibility of 98%, 95%, 98% and 100% respectively. Overall, 99 isolates among Enterobacteriaceae (E. coli, Klebsiella spp. and Enterobacter spp.) were ESBL producers, susceptible to tigecycline. Among the 101 meropenem resistant Enterobacteriaceae, 85 were susceptible to tigecycline (84%). Among the Gram-positive bacteria, S. aureus and Enterococcus spp. were 99% and 98% susceptible to tigecycline respectively. Among 68 MRSA isolates in the study, 66 (97%) were susceptible to tigecycline. Seven vancomycin resistant E. faecalis were isolated and all were susceptible to tigecycline. Conclusion: Tigecycline has retained activity over both Gram-positive and Gram-negative organisms with MIC values comparable to global reports. About 98% of the MDR Gram-positive and Gram-negative bacteria in the study are susceptible to tigecycline. With increased incidence of extensively drug resistant organisms, tigecycline is a potential reserve drug.

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