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Jocelyne Caillon

Publications and source records attributed to Jocelyne Caillon.

At least 19 recordsLinked to original sources

Trough serum concentrations of beta-lactam antibiotics in cancer patients: inappropriateness of conventional schedules to pharmacokinetic/pharmacodynamic properties of beta-lactams.

Serum concentrations of beta-lactams that continuously exceed the minimum inhibitory concentration may improve therapeutic outcomes for immunosuppressed patients. The trough serum levels of ceftazidime (CAZ), cefepime (FEP) or imipenem (IMP) were prospectively determined on days 1 and 3 of treatment in cancer patients. Seventy-eight episodes of suspected infection were analysed. Trough serum levels were higher than 4 mg/L in 62%, 24% and 0% of cases in the CAZ, FEP and IMP groups, respectively, and were higher than 20 mg/L in 24% of cases in the CAZ group compared with 0% both in the FEP and IMP groups. For suspected infectious episodes in cancer patients, the traditional intermittent regimen of beta-lactams does not appear to be appropriate for the pharmacokinetic/pharmacodynamic properties of these antibiotics.

Adult↗

Effectiveness of linezolid and imipenem association in the treatment of severe community-acquired pneumonia in children: two case reports.

Two children with severe pneumonia, purulent pleural effusions, and abscess formation unresponsive to appropriate antibiotic therapy recovered promptly after the introduction of linezolid and imipenem association. Linezolid is a new antibiotic with high bioavailability and an outstanding safety profile, synergistic with imipenem, which may deserve a place in the armamentarium for severe pneumonia in children.

Acetamides↗

In vitro and in vivo assessment of linezolid combined with ertapenem: a highly synergistic combination against methicillin-resistant Staphylococcus aureus.

Linezolid in combination with ertapenem showed in vitro synergy against methicillin-resistant Staphylococcus aureus strains. We confirmed this interaction in vivo by using a rabbit endocarditis experimental model and simulation of the human pharmacokinetics in animals for both antibiotics. Linezolid plus ertapenem exhibited highly synergistic activity in vivo after 4 days of treatment.

Acetamides↗

Eagle effect in Corynebacterium diphtheriae.

The in vivo relevance of the paradoxical bactericidal effect (the Eagle effect) is not evident. We found in vitro a paradoxical bactericidal effect of amoxicillin on 2 strains of nontoxigenic Corynebacterium diphtheriae. Then, using an experimental rabbit model of endocarditis, we evaluated the in vivo relevance of this phenomenon. Rabbits were assigned to the following groups: no treatment (control group), continuous amoxicillin infusion simulating a dosage of 200 mg/kg/day in humans, and continuous amoxicillin infusion simulating a dosage of 20 mg/kg/day in humans. The low dosage (20 mg/kg/day) was significantly more effective than the high dosage (200 mg/kg/day) against both strains (P<.025), confirming the paradoxical bactericidal effect observed in vitro.

Amoxicillin↗

Surgical-site infection after cardiac surgery: incidence, microbiology, and risk factors.

OBJECTIVE: To identify risk factors associated with surgical-site infection according to the depth of infection, the cardiac procedure, and the National Nosocomial Infections Surveillance System risk index. DESIGN: Prospective survey conducted during a 12-month period. SETTING: A 48-bed cardiac surgical department in a teaching hospital. PATIENTS: Patients admitted for cardiac surgery between February 2002 and January 2003. RESULTS: Surgical-site infections were diagnosed in 3% of the patients (38 of 1,268). Of the 38 surgical-site infections, 20 were superficial incisional infections and 18 were mediastinitis for incidence rates of 1.6% and 1.4%, respectively. Cultures were positive in 28 cases and the most commonly isolated pathogen was Staphylococcus. A National Nosocomial Infections Surveillance System risk index score of 2 or greater was associated with a risk of surgical-site infection (relative risk, 2.4; P < .004). Heart transplantation, mechanical circulatory assistance, coronary artery bypass graft with the use of internal mammary artery, and reoperation for cardiac tamponade or pericard effusion were independent risk factors associated with surgical-site infection. CONCLUSIONS: Data surveillance using incidence rates stratified by cardiac procedure and type of infection is relevant to improving infection control efforts. Risk factors in patients who developed superficial infection were different from those in patients who developed mediastinitis. Coronary artery bypass graft using internal mammary artery was associated with a high risk of surgical-site infection, and independent factors such as reoperation for cardiac tamponade or pericard effusion increased the risk of infection.

Adolescent↗

Acute severe spinal cord dysfunction in a child with meningitis: Streptococcus pneumoniae and Mycoplasma pneumoniae co-infection.

UNLABELLED: Tetraplegia developed abruptly in an 11-y-old with pneumococcal meningitis. Magnetic resonance imaging showed multiple hyperintensities at the brainstem-spinal cord junction. Serological tests were positive for Mycoplasma pneumoniae (microparticle agglutination and specific IgMs). Erythromycin and dexamethasone were started promptly, and 10 d later the patient was discharged with normal neurological function. CONCLUSION: Tetraplegia during the course of pneumococcal meningitis in an 11-y-old girl disappeared after treatment with ceftriaxone, erythromycin and dexamethasone.

Anti-Bacterial Agents↗

In vitro and in vivo synergistic activities of linezolid combined with subinhibitory concentrations of imipenem against methicillin-resistant Staphylococcus aureus.

Indifference or moderate antagonism of linezolid combined with other antibiotics in vitro and in vivo have mainly been reported in the literature. We have assessed the in vitro activities of linezolid, alone or in combination with imipenem, against methicillin-resistant Staphylococcus aureus (MRSA) strains using the dynamic checkerboard and time-kill curve methods. Linezolid and low concentrations of imipenem had a synergistic effect, leading us to evaluate the in vivo antibacterial activity of the combination using the rabbit endocarditis experimental model. Two MRSA strains were used for in vivo experiments: one was a heterogeneous glycopeptide-intermediate clinical S. aureus strain isolated from blood cultures, and the other was the S. aureus COL reference strain. Animals infected with one of two MRSA strains were randomly assigned to one of the following treatments: no treatment (controls), linezolid (simulating a dose in humans of 10 mg/kg of body weight every 12 h), a constant intravenous infusion of imipenem (which allowed the steady-state concentration of about 1/32 the MIC of imipenem for each strain to be reached in serum), or the combination of both treatments. Linezolid and imipenem as monotherapies exhibited no bactericidal activity against either strain. The combination of linezolid plus imipenem showed in vivo bactericidal activity that corresponded to a decrease of at least 4.5 log CFU/g of vegetation compared to the counts for the controls. In conclusion, the combination exhibited synergistic and bactericidal activities against two MRSA strains after 5 days of treatment. The combination of linezolid plus imipenem appears to be promising for the treatment of severe MRSA infections and merits further investigations to explore the mechanism underlying the synergy between the two drugs.

Acetamides↗

Activity of glycopeptides against Staphylococcus aureus infection in a rabbit endocarditis model: MICs do not predict in vivo efficacy.

The in vivo efficacy of vancomycin and teicoplanin against five Staphylococcus aureus strains with different susceptibilities to them and methicillin was studied. Rabbits were allocated at random to groups for endocarditis induction with one of these five strains and then treated for 2 days with vancomycin or teicoplanin. Each treated group was compared with a control group infected with the same strain. Vancomycin and teicoplanin showed similar activities. Low MICs did not predict better in vivo results.

Animals↗

In vitro and in vivo bactericidal activities of vancomycin dispersed in porous biodegradable poly(epsilon-caprolactone) microparticles.

Treatment of methicillin-resistant Staphylococcus aureus osteomyelitis requires a prolonged antibiotic therapy with vancomycin. Because of its weak diffusion, the in situ implantation of vancomycin could be interesting. The activity of vancomycin encapsulated in microparticles was evaluated in vitro and in vivo on rabbit osteomyelitis and showed a good activity compared to intravenous administration.

Animals↗

Comparison of in vivo intrinsic activity of cefepime and imipenem in a Pseudomonas aeruginosa rabbit endocarditis model: effect of combination with tobramycin simulating human serum pharmacokinetics.

OBJECTIVES: The purpose of this experimental study was first to compare the in vivo intrinsic activity of imipenem and cefepime administered as a continuous infusion and to determine their lowest effective serum steady-state concentration (LESSC). Secondly, we studied the effect of combining therapy with tobramycin. METHODS: In a Pseudomonas aeruginosa (ATCC 27853) rabbit endocarditis model, beta-lactam antibiotics were administered by continuous infusion over a 24 h treatment period at different doses until the LESSC was reached, i.e. able to achieve a 2-log drop of cfu/g of vegetations versus untreated animals. The effect of adding tobramycin (3 mg/kg once daily) was then studied. RESULTS: The LESSC was between 3 x and 4 x MIC of cefepime for P. aeruginosa and about 0.2 5x MIC of imipenem. Combination of tobramycin with each of the two beta-lactams did not result in any further significant killing. CONCLUSION: The optimal Css/MIC ratio might differ from one molecule to another. The LESSC of imipenem is lower than that of cefepime, giving a better intrinsic activity in vivo, despite a higher MIC in vitro.

Animals↗

Post-antibiotic and post-beta-lactamase inhibitor effects of ceftazidime plus sulbactam on extended-spectrum beta-lactamase-producing Gram-negative bacteria.

OBJECTIVES: To measure the in vitro post-antibiotic effect (PAE) and post-beta-lactamase inhibitor effect (PLIE) of a ceftazidime-sulbactam combination on bacteria producing extended-spectrum beta-lactamases (ESBLs). METHODS: PAE and PLIE were studied for ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Two ATCC beta-lactamase-negative strains of E. coli and K. pneumoniae were used as controls. The MICs of a ceftazidime-sulbactam combination were determined with a fixed concentration of sulbactam (8 mg/L). The organisms were exposed to the antibiotics at twice the MIC for 2 h before removal of the antibiotics by filtration of the culture. Bacteria on the filter were resuspended in drug-free medium to determine the PAE and in medium containing ceftazidime, at the same concentration as originally present, to determine the PLIE. RESULTS: The PAE of ceftazidime was similar for bacteria producing the same ESBL except for E. coli producing CTX-M-1. PLIE values varied according to the type of beta-lactamase but similar results were observed for the strains producing the same ESBLs. PLIEs were longer than PAEs and were longer when the MICs of ceftazidime were lower. CONCLUSIONS: To the best of our knowledge, we describe here for the first time an in vitro PLIE for a ceftazidime-sulbactam combination on different bacteria producing different ESBLs. These findings indicate that suicide inhibitors may be used in combination with third-generation cephalosporins.

Anti-Bacterial Agents↗

Detection of an IS21 insertion sequence in the mexR gene of Pseudomonas aeruginosa increasing beta-lactam resistance.

To understand the regulation of the MexAB OprM efflux system in a clinical strain of Pseudomonas aeruginosa presenting a decreased susceptibility to ticarcillin and aztreonam, the mexR repressor gene was amplified by polymerase chain reaction (PCR) and was shown to be disrupted by an insertion sequence of more than 2 kb, with characteristic direct and inverted repeat sequences. Sequencing revealed a 2131-bp IS21 insertion sequence. A reverse transcription PCR method was used to quantify mexA transcripts and showed an increased transcription rate of mexA in this strain, compared with a PAO1 control strain. The nalB phenotype in P. aeruginosa may be due to point mutations, but also to the presence of an insertion sequence in the mexR regulator gene.

Bacterial Outer Membrane Proteins↗

In vivo efficacy of linezolid in combination with gentamicin for the treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Indifference or even antagonism has mainly been reported with combinations including linezolid. The presence of in vitro antagonism is not always correlated with in vivo failure. The purpose of this study was to evaluate the in vivo activity of linezolid combined with gentamicin using a methicillin-resistant Staphylococcus aureus (MRSA) endocarditis experimental model. A human-like pharmacokinetic simulation was used for linezolid and gentamicin to improve the extrapolation of the results to human therapy. Contrary to the antagonism previously described in vitro, linezolid combined with gentamicin exhibited bactericidal activity on the two strains with a decrease of at least 4 log(10)cfu/g of vegetation compared with controls. These data suggest that linezolid plus gentamicin could be an appropriate combination for the treatment of severe MRSA infections.

Acetamides↗

[Antibiotic therapy: from pharmacology to decision making].

The decision of an antibiotic treatment depends first on clinical and bacteriological data. Then PK/PD (pharmacodynamics/pharmacokinetics) of antibiotics must be taken into account in order to optimise the dosing regimen, and to reach the targeted serum concentrations. The good oral bioavailability of some drugs allows the use of the oral route, at the beginning of the treatment, or shortly after an initial successful i.v. administration, even in severe infections.

Anti-Bacterial Agents↗

In vitro activity of linezolid alone and in combination with gentamicin, vancomycin or rifampicin against methicillin-resistant Staphylococcus aureus by time-kill curve methods.

The in vitro activity of the oxazolidinone linezolid was studied alone and in combination with three antibiotics acting on different cellular targets. Oxazolidinones are bacterial protein synthesis inhibitors that act at a very early stage by preventing the formation of the initiation complex. Combinations of linezolid with gentamicin, vancomycin or rifampicin were evaluated against four methicillin-resistant Staphylococcus aureus strains, using killing curves in conjunction with scanning electron microscopy. Time-kill curves were performed over 24 h using an inoculum of 5 x 10(6)- 1 x 10(7) cfu/mL. Linezolid was studied at concentrations of 1 x, 4 x and 8 x MIC, with partner drugs at 8 x MIC. Addition of linezolid resulted in a decrease of antibacterial activity for gentamicin and vancomycin, and linezolid was antagonistic to the early bactericidal activity of gentamicin. Linezolid, in combination with rifampicin, showed an additive interaction for susceptible strains and inhibited rifampicin-resistant variants. Linezolid plus rifampicin appeared to be the most active combination against methicillin-resistant S. aureus strains in time-kill experiments.

Acetamides↗

Simulation of human gentamicin pharmacokinetics in an experimental Enterococcus faecalis endocarditis model.

Significant differences between animal and human pharmacokinetics may be responsible for the conflicting results of experimental studies. This study determined the impact of human pharmacokinetic simulation (HPS) on gentamicin activity in an Enterococcus faecalis endocarditis model. The decrease in bacterial counts was greater with HPS than with a dose-equivalent regimen without HPS.

Animals↗