scholarly journals In Vitro Activities of Oral β-Lactams at Concentrations Achieved in Humans against Penicillin-Susceptible and -Resistant Pneumococci and Potential to Select Resistance

1998 ◽  
Vol 42 (8) ◽  
pp. 1973-1979 ◽  
Author(s):  
Christine E. Thorburn ◽  
Sarah J. Knott ◽  
David I. Edwards
Keyword(s):  
Streptococcus Pneumoniae ◽  
Bactericidal Effect ◽  
Penicillin G ◽  
Cross Resistance ◽  
Dosing Interval ◽  
Middle Ear Fluid ◽  
Amoxicillin Clavulanate ◽  
Time Kill ◽  
Repeated Subculture

ABSTRACT The β-lactam susceptibilities of 65 strains ofStreptococcus pneumoniae for which penicillin MICs covered a broad range were assessed. The order of potency was amoxicillin (AMX) = amoxicillin-clavulanate (AMC) > penicillin G > cefpodoxime (CPO) > cefuroxime (CXM) > cefprozil > cefaclor > loracarbef > cefixime. No decrease in susceptibility was seen following repeated subculture of two penicillin-susceptible strains of S. pneumoniae in AMX, AMC, cefaclor, or loracarbef, whereas repeated exposure to CPO and CXM resulted in 4- to 32-fold decreases in susceptibility for both strains. When one of these strains was exposed to concentrations of CPO, CXM, AMX, and AMC achieved in the serum of humans following the administration of an oral dose, all agents were rapidly bactericidal, with no decrease in susceptibility up to 72 h. This was consistent with antibiotic concentrations exceeding the MICs for 100% of the dosing interval. For a penicillin-resistant strain, MICs were exceeded for 29% of the 12-h dosing interval for 500 mg of AMX, 42% of the interval for AMC with 875 mg of AMX and 125 mg of clavulanate (875/125 mg of AMC) 21% of the interval for 500 mg of CXM, and 0% of the interval for 200 mg of CPO. Consequently, only 875/125 mg of AMC produced a sustained bactericidal effect. A four- to eightfold reduction in susceptibility to CPO and CXM and cross-resistance with cefotaxime, but not penicillin or AMC, were selected following exposure to simulated serum CPO and CXM concentrations. In addition, AMX and AMC were the only agents which consistently produced a >99% reduction in bacterial numbers in time-kill studies using concentrations of antibiotic achieved in middle ear fluid for all three strains of penicillin-resistant S. pneumoniae tested.

scholarly journals Comparison of the In Vitro Efficacies of Moxifloxacin and Amoxicillin against Listeria monocytogenes

2008 ◽  
Vol 52 (5) ◽  
pp. 1697-1702 ◽  
Author(s):  
S. Grayo ◽  
O. Join-Lambert ◽  
M. C. Desroches ◽  
A. Le Monnier
Keyword(s):  
Listeria Monocytogenes ◽  
Bactericidal Effect ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Gram Positive Bacteria ◽  
Severe Infections ◽  
Potential Alternative ◽  
Kill Curve ◽  
Time Kill

ABSTRACT Listeria monocytogenes is a facultative intracellular bacterium that causes severe infections associated with a high mortality rate. Moxifloxacin presents extended activity against gram-positive bacteria and has recently been suggested to be a potential alternative in the treatment of listeriosis. We evaluated the in vitro efficacy of moxifloxacin against L. monocytogenes using a combination of epidemiological and experimental approaches. The median MIC of moxifloxacin for a large collection of L. monocytogenes strains of various origins (human, food, and environment) was 0.5 μg/ml (MIC range, 0.064 to 1 μg/ml). No differences were observed, irrespective of the origin of the strains. Moreover, no cross-resistance with fluoroquinolones was detected in strains that have been reported to be resistant to ciprofloxacin. The in vitro activities of moxifloxacin and amoxicillin were compared by time-kill curve and inhibition of intracellular growth experiments by using a model of bone marrow-derived mouse macrophages infected by L. monocytogenes EGDe. Both moxifloxacin and amoxicillin were bactericidal in broth against extracellular forms of L. monocytogenes. However, moxifloxacin acted much more rapidly, beginning to exert its effects in the first 3 h and achieving complete broth sterilization within 24 h of incubation. Moxifloxacin has a rapid bactericidal effect against intracellular reservoirs of bacteria, whereas amoxicillin is only bacteriostatic and appears to prevent cellular lysis and the subsequent bacterial spreading to adjacent cells. No resistant bacteria were selected during the in vitro experiments. Taken together, our results suggest that moxifloxacin is an interesting alternative to the reference treatment, combining rapid and bactericidal activity, even against intracellular bacteria.

scholarly journals In Vitro Bactericidal Activities of ABT-773 against ermB Strains of Streptococcus pneumoniae

2003 ◽  
Vol 47 (3) ◽  
pp. 1132-1134 ◽  
Author(s):  
Melinda M. Neuhauser ◽  
Jennifer L. Prause ◽  
Larry H. Danziger ◽  
Susan L. Pendland
Keyword(s):  
Streptococcus Pneumoniae ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Mueller Hinton ◽  
Amoxicillin Clavulanate ◽  
Horse Blood ◽  
Bactericidal Activities ◽  
Time Kill ◽  
Mueller Hinton Broth

ABSTRACT The bactericidal activities of ABT-773, a new ketolide, were compared to those of cefuroxime and amoxicillin-clavulanate against 10 strains of Streptococcus pneumoniae containing the ermB gene. MICs and time-kill curves were determined in duplicate per NCCLS guidelines with cation-adjusted Mueller-Hinton broth with 3% lysed horse blood. Viable counts were done at 0, 2, 6, and 24 h. Antibiotic concentrations tested were two and eight times the MIC. ABT-773 MICs ranged from 0.008 to 1.0 μg/ml. Bactericidal activity was observed with ABT-773 at eight times the MIC against 4 of 10 strains at 24 h compared to 10 of 10 strains with the beta-lactam antibiotics.

scholarly journals THE RATE OF BACTERICIDAL ACTION OF PENICILLIN IN VITRO AS A FUNCTION OF ITS CONCENTRATION, AND ITS PARADOXICALLY REDUCED ACTIVITY AT HIGH CONCENTRATIONS AGAINST CERTAIN ORGANISMS

1948 ◽  
Vol 88 (1) ◽  
pp. 99-131 ◽  
Author(s):  
Harry Eagle ◽  
A. D. Musselman
Keyword(s):  
Bacterial Species ◽  
Fold Increase ◽  
Bactericidal Effect ◽  
Penicillin G ◽  
Bacterial Suspension ◽  
Maximal Effect ◽  
Maximal Rate ◽  
Effective Level ◽  
High Concentrations

1. The concentrations of penicillin G which (a) reduced the net rate of multiplication, (b) exerted a net bactericidal effect, and (c) killed the organisms at a maximal rate, have been defined for a total of 41 strains of α- and ß-hemolytic streptococci, Staphylococcus aureus and Staphylococcus albus, Diplococcus pneumoniae, and the Reiter treponoma. 2. The concentration which killed the organisms at a maximal rate was 2 to 20 times the minimal effective level ("sensitivity" as ordinarily defined). With some organisms, even a 32,000-fold increase beyond this maximally effective level did not further increase the rate of its bactericidal effect. However, with approximately half the strains here studied (all 4 strains of group B ß-hemolytic streptococci, 4 of 5 group C strains, 5 of 7 strains of Streptococcus fecalis, 2 of 4 other α-hemolytic streptococci, and 4 of 9 strains of staphylococci), when the concentration of penicillin was increased beyond that optimal level, the rate at which the organisms died was paradoxically reduced rather than increased, so that the maximal effect was obtained only within a relatively narrow optimal zone. 3. There were marked differences between bacterial species, and occasionally between different strains of the same species, not only with respect to the effective concentrations of penicillin, but also with respect to the maximal rate at which they could be killed by the drug in any concentration. Although there was a rough correlation between these two factors, there were many exceptions; individual strains affected only by high concentrations of penicillin might nevertheless be killed rapidly, while strains sensitive to minute concentrations might be killed only slowly. 4. Within the same bacterial suspension, individual organisms varied only to a minor degree with respect to the effective concentrations of penicillin. They varied strikingly, however, in their resistance to penicillin as measured by the times required to kill varying proportions of the cells.

scholarly journals Antimicrobial Properties of 8-Hydroxyserrulat-14-en-19-oic Acid for Treatment of Implant-Associated Infections

2012 ◽  
Vol 57 (1) ◽  
pp. 333-342 ◽  
Author(s):  
Justyna Nowakowska ◽  
Hans J. Griesser ◽  
Marcus Textor ◽  
Regine Landmann ◽  
Nina Khanna
Keyword(s):  
Structural Changes ◽  
Treatment Options ◽  
Antimicrobial Properties ◽  
Bactericidal Effect ◽  
Mouse Tissue ◽  
Logarithmic Phase ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Time Kill

ABSTRACTTreatment options are limited for implant-associated infections (IAI) that are mainly caused by biofilm-forming staphylococci. We report here on the activity of the serrulatane compound 8-hydroxyserrulat-14-en-19-oic acid (EN4), a diterpene isolated from the Australian plantEremophila neglecta. EN4 elicited antimicrobial activity toward various Gram-positive bacteria but not to Gram-negative bacteria. It showed a similar bactericidal effect against logarithmic-phase, stationary-phase, and adherentStaphylococcus epidermidis, as well as against methicillin-susceptible and methicillin-resistantS. aureuswith MICs of 25 to 50 μg/ml and MBCs of 50 to 100 μg/ml. The bactericidal activity of EN4 was similar againstS. epidermidisand its Δicamutant, which is unable to produce polysaccharide intercellular adhesin-mediated biofilm. In time-kill studies, EN4 exhibited a rapid and concentration-dependent killing of staphylococci, reducing bacterial counts by >3 log10CFU/ml within 5 min at concentrations of >50 μg/ml. Investigation of the mode of action of EN4 revealed membranolytic properties and a general inhibition of macromolecular biosynthesis, suggesting a multitarget activity.In vitro-tested cytotoxicity on eukaryotic cells was time and concentration dependent in the range of the MBCs. EN4 was then tested in a mouse tissue cage model, where it showed neither bactericidal nor cytotoxic effects, indicating an inhibition of its activity. Inhibition assays revealed that this was caused by interactions with albumin. Overall, these findings suggest that, upon structural changes, EN4 might be a promising pharmacophore for the development of new antimicrobials to treat IAI.

scholarly journals 1582. Delafloxacin Activity Against Drug-Resistant Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis from US Medical Centers (2014–2018)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S577-S578
Author(s):  
Dee Shortridge ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Robert K Flamm
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Moraxella Catarrhalis ◽  
Active Agent ◽  
The United States ◽  
Multidrug Resistant ◽  
In Vitro Susceptibility ◽  
Amoxicillin Clavulanate ◽  
Tract Infections

Abstract Background Delafloxacin (DLX) is an anionic fluoroquinolone (FQ) antimicrobial that was approved in 2017 by the United States (US) Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections. DLX recently successfully completed a clinical trial for the treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from US hospitals participating in the SENTRY Program during 2014–2018. Methods A total of 1,975 SPN, 1,128 HI, 684 MC, and 43 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014–2018 from US hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and CLSI (2019) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin, and tetracycline; other SPN phenotypes were LEV-NS or penicillin (PEN)-NS. β-Lactamase (BL) presence was determined for HI, HP, and MC. Results The activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were similar when tested against the MDR or PEN-NS for SPN phenotypes. LEV-NS isolates had DLX MIC50/90 results of 0.12/0.25 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 2 HP isolates were BL-positive. Conclusion DLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. DLX had excellent activity against LEV-NS SPN. These data support the continued study of DLX as a potential treatment for CABP. Disclosures All authors: No reported disclosures.

scholarly journals β-Lactamase Production in Prevotella intermedia,Prevotella nigrescens, and Prevotella pallensGenotypes and In Vitro Susceptibilities to Selected Antimicrobial Agents

1999 ◽  
Vol 43 (10) ◽  
pp. 2383-2388 ◽  
Author(s):  
Jaana Mättö ◽  
Sirkka Asikainen ◽  
Marja-Liisa Väisänen ◽  
Birgitta Von Troil-Lindén ◽  
Eija Könönen ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
The United States ◽  
Penicillin G ◽  
Prevotella Intermedia ◽  
Geographic Locations ◽  
Prevotella Nigrescens ◽  
Amoxicillin Clavulanate ◽  
Arbitrarily Primed Pcr ◽  
Negative Population

ABSTRACT The present study investigated the β-lactamase production of 73Prevotella intermedia, 84 Prevotella nigrescens, and 14 Prevotella pallens isolates and their in vitro susceptibilities to six antimicrobial agents. TheP. intermedia and P. nigrescens isolates were recovered from oral and extraoral samples obtained from subjects in two geographic locations from 1985 to 1995. The clonality of the β-lactamase-positive and β-lactamase-negative isolates and the clustering of the genotypes were studied by arbitrarily primed-PCR fingerprinting. β-Lactamase production was detected in 29% ofP. intermedia isolates, 29% of P. nigrescensisolates, and 57% of P. pallens isolates. No difference in the frequencies of β-lactamase production by P. intermedia and P. nigrescens between isolates from oral and extraoral sites, between isolates obtained at different time periods, or between P. intermedia isolates from different geographic locations was observed. However, the P. nigrescens isolates from the United States were significantly more frequently (P = 0.015) β-lactamase positive than those from Finland. No association between the genotypes and β-lactamase production or between the genotypes and the sources of the isolates was found. The penicillin G MICs at which 90% of the isolates were inhibited were 8 μg/ml for P. intermedia, 8 μg/ml for P. nigrescens, and 16 μg/ml for P. pallens. For the β-lactamase-negative isolates, the corresponding values were 0.031, 0.031, and 0.125 μg/ml, and for the β-lactamase-positive isolates, the corresponding values were 16, 8, and 32 μg/ml. All isolates were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, azithromycin, and trovafloxacin. The MICs of amoxicillin-clavulanate and cefoxitin were relatively higher for the β-lactamase-positive population than for the β-lactamase-negative population.

scholarly journals In Vitro Activities of Garenoxacin (BMS-284756) against Streptococcus pneumoniae, Viridans Group Streptococci, and Enterococcus faecalis Compared to Those of Six Other Quinolones

2003 ◽  
Vol 47 (11) ◽  
pp. 3542-3547 ◽  
Author(s):  
Patrick Grohs ◽  
Serge Houssaye ◽  
Agnès Aubert ◽  
Laurent Gutmann ◽  
Emmanuelle Varon
Keyword(s):  
Streptococcus Pneumoniae ◽  
Enterococcus Faecalis ◽  
Bactericidal Effect ◽  
Clinical Isolates ◽  
Active Efflux ◽  
Resistant Strains ◽  
Different Strains ◽  
Viridans Group Streptococci ◽  
Derivatives Of

ABSTRACT The activity of garenoxacin, a new quinolone, was determined in comparison with other quinolones against different strains of S. pneumoniae, viridans group streptococci (VGS), and Enterococcus faecalis. Strains were quinolone-susceptible clinical isolates and quinolone-resistant strains with defined mechanisms of resistance obtained from either clinical isolates or derivatives of S. pneumoniae R6. Clinical quinolone-susceptible strains of S. pneumoniae, VGS and E. faecalis showed garenoxacin MICs within a range of 0.03 μg/ml to 0.25 μg/ml. Garenoxacin MICs increased two- to eightfold when one mutation was present in the ParC quinolone resistance-determining region (QRDR), fourfold when one mutation was present in the GyrA QRDR (S. pneumoniae), 8- to 64-fold when two or three mutations were associated in ParC and GyrA QRDR, and 2,048-fold when two mutations were present in both the GyrA and ParC QRDRs (Streptococcus pneumoniae). Increased active efflux had a moderate effect on garenoxacin MICs for S. pneumoniae and VGS. Against S. pneumoniae, garenoxacin behaved like moxifloxacin and sparfloxacin, being more affected by a single gyrA mutation than by a single parC mutation. Although garenoxacin was generally two- to fourfold more active than moxifloxacin against the different wild-type or mutant strains of S. pneumoniae, VGS, and E. faecalis, it was two- to fourfold less active than gemifloxacin. At four times the respective MIC for each strain, the bactericidal effect of garenoxacin, observed at 6 h for S. pneumoniae and at 24 h for S. oralis and E. faecalis, was not influenced by the presence of mutation either in the ParC or in both the ParC and GyrA QRDRs.

scholarly journals Activities of Newer Fluoroquinolones against Ciprofloxacin-Resistant Streptococcus pneumoniae

2001 ◽  
Vol 45 (6) ◽  
pp. 1654-1659 ◽  
Author(s):  
Elizabeth A. Coyle ◽  
Glenn W. Kaatz ◽  
Michael J. Rybak
Keyword(s):  
Streptococcus Pneumoniae ◽  
Efflux Pump ◽  
Specific Area ◽  
Cross Resistance ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Time Curve ◽  
Ciprofloxacin Resistance ◽  
Derivatives Of

ABSTRACT The incidence of ciprofloxacin resistance in Streptococcus pneumoniae is low but steadily increasing, which raises concerns regarding the clinical impact of potential cross-resistance with newer fluoroquinolones. To investigate this problem, we utilized an in vitro pharmacodynamic model and compared the activities of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin to that of ciprofloxacin against two laboratory-derived, ciprofloxacin-resistant derivatives of S. pneumoniae (strains R919 and R921). Ciprofloxacin resistance in these strains involved the activity of a multidrug efflux pump and possibly, for R919, a mutation resulting in an amino acid substitution in GyrA. Gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin achieved 99.9% killing of both R919 and R921 in ≤28 h. With respect to levofloxacin, significant regrowth of both mutants was observed at 48 h (P < 0.05). For gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin, regrowth was minimal at 48 h, with each maintaining 99.9% killing against both mutants. No killing of either R919 or R921 was observed with exposure to ciprofloxacin. During model experiments, resistance to gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin did not develop but the MICs of ciprofloxacin and levofloxacin increased 1 to 2 dilutions for both R919 and R921. Although specific area under the concentration-time curve from 0 to 24 h (AUC0–24)/MIC and maximum concentration of drug in serum (C max)/MIC ratios have not been defined for the fluoroquinolones with respect to gram-positive organisms, our study revealed that significant regrowth and/or resistance was associated with AUC0–24/MIC ratios of ≤31.7 and C max/MIC ratios of ≤3.1. It is evident that the newer fluoroquinolones tested possess improved activity against S. pneumoniae, including strains for which ciprofloxacin MICs were elevated.

scholarly journals In vitro selection of mutants of Streptococcus pneumoniae resistant to macrolides and linezolid: relationship with susceptibility to penicillin G or macrolides

2005 ◽  
Vol 56 (4) ◽  
pp. 633-642 ◽  
Author(s):  
H. Carsenti-Dellamonica ◽  
M. Galimand ◽  
F. Vandenbos ◽  
C. Pradier ◽  
P. M. Roger ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
In Vitro Selection ◽  
Penicillin G ◽  
Selection Of

scholarly journals Pulmonary Damage and Bacterial Load in Assessment of the Efficacy of Simulated Human Treatment-Like Amoxicillin (2,000 Milligrams) Therapy of Experimental Pneumococcal Pneumonia Caused by Strains for Which Amoxicillin MICs Differ

2005 ◽  
Vol 49 (3) ◽  
pp. 996-1001 ◽  
Author(s):  
Matilde Gracia ◽  
Carmina Martínez-Marín ◽  
Lorena Huelves ◽  
Maria J. Giménez ◽  
Lorenzo Aguilar ◽  
...  
Keyword(s):  
Bacterial Load ◽  
In Vitro Study ◽  
In Vivo Model ◽  
Lung Weight ◽  
End Points ◽  
Dosing Interval ◽  
Pulmonary Damage ◽  
Amoxicillin Clavulanate

ABSTRACT An experimental rat pneumonia model using two amoxicillin-susceptible (MICs, ≤0.015 and 2 μg/ml) and two non-amoxicillin-susceptible (MIC, 4 μg/ml) Streptococcus pneumoniae strains was developed for testing the efficacy of amoxicillin administered to simulate human serum kinetics after treatment with amoxicillin-clavulanate (2,000 and 125 mg, respectively, twice a day, for 2.5 days). The end points for efficacy were reductions in bacterial loads in the lungs and reductions in levels of pulmonary damage. For the amoxicillin-susceptible strains (serotypes 23F and 14), a decrease greater than 4.5 log10 CFU/pair of lungs was obtained, and the time for which the serum antibiotic concentration (SAC) was higher than the MIC (T S A C > MIC) was greater than 60% of the dosing interval. For non-amoxicillin-susceptible strains, the decrease in bacterial load was 1.34 to 1.75 log10 CFU/pair of lungs, with a T S A C > MIC of 46.7% of the dosing interval. An in vitro study showed that serotype 9V non-amoxicillin-susceptible strains behaved as tolerant-like to concentrations similar to those in the in vivo model. The high and maintained SACs (T S A C > MIC, >46% for all strains) significantly diminished lung injury (affected area of the lung and lung weight), compared to that in controls, by all strains, regardless of the MIC, bactericidal behavior in in vitro killing curves, or the serotype of the infecting strain. These results show the importance of host therapeutic end points in the evaluation of antibiotic efficacy. The antibiotic was more efficacious, for one nonsusceptible strain tested, when the treatment was started early (1 h postinoculation [p.i.]) than when treatment was delayed (24 h p.i.).

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