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Biomedical subjects

O Mimoz

Publications and source records attributed to O Mimoz.

At least 37 records · Page 2Linked to original sources

Treatment of experimental pneumonia in rats caused by a PER-1 extended-spectrum beta-lactamase-producing strain of Pseudomonas aeruginosa.

The antibacterial activity of imipenem, cefepime and piperacillin-tazobactam alone or in combination with amikacin against a Pseudomonas aeruginosa strain producing an extended-spectrum beta-lactamase (PER-1) were compared using an experimental model of pneumonia in non-leucopenic rats. Animals were infected intratracheally with 8.0 +/- 0.4 log10 cfu of P. aeruginosa, and therapy was initiated 3 h later, by which time animal lungs showed bilateral pneumonia containing >7 log10 P. aeruginosa cfu/g of tissue. Since rats eliminate antibiotics much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters of humans. MICs determined using an inoculum of 4 log10 cfu/mL were as follows: imipenem, 1 mg/L; cefepime, 8 mg/L; piperacillin-tazobactam, 32 mg/L; and amikacin, 16 mg/L. A noticeable inoculum effect was observed with the four antimicrobial agents tested, which was greatest for cefepime and piperacillin-tazobactam. In-vitro studies indicated that imipenem was the beta-lactam with the greatest bactericidal effect and that amikacin was synergic only in combination with cefepime and imipenem. Cefepime and piperacillin-tazobactam alone failed to decrease bacterial counts in the rats' lungs 60 h after therapy onset, whereas imipenem and, to a lesser extent, amikacin significantly reduced the number of viable microorganisms. Combination of amikacin with any of the three beta-lactams tested was synergic, despite a high amikacin MIC for the infecting strain. These results paralleled our in-vitro data showing a marked inoculum effect for cefepime and piperacillin-tazobactam. Based on the results of this study, the best treatment for infections caused by this type of extended-spectrum beta-lactamase-possessing strain would be imipenem plus amikacin.

Amikacin↗

Procalcitonin and C-reactive protein during the early posttraumatic systemic inflammatory response syndrome.

OBJECTIVES: To describe the initial evolution of serum procalcitonin (PCT) and C-reactive protein (CRP) in previously healthy adult trauma patients and to compare the relationship of the expression of these two proteins with indicators of trauma severity. DESIGN: Prospective, descriptive, longitudinal study. SETTING: Surgical ICU in an university hospital. PATIENTS: Twenty-one patients admitted during the first posttraumatic 3 h exhibiting an Injury Severity Score (ISS) between 16 and 50 were enrolled. MEASUREMENTS: Blood sampling was performed on admission and on posttraumatic days 0.5, 1, 2 and 3 to assess serum levels of PCT and CRP. Total creatine kinase (CKtot) and lactate dehydrogenase (LDHtot) activities in the serum were used as tissue damage indicators. RESULTS: PCT exhibited an early and transient increase in serum levels similar to a more delayed change of CRP levels. Peak PCT and peak CRP were related to the ISS, the extent of tissue damage and the amount of fluid replacement during the first day. During the first 3 posttraumatic days, 90% of the patients exhibited a generalized inflammatory syndrome without infection. CONCLUSIONS: An early and transient release of PCT into the circulation was observed after severe trauma and the amount of circulating PCT seemed proportional to the severity of tissue injury and hypovolemia, yet unrelated to infection. The predictive value of both PCT and CRP for a forthcoming multiple organ failure still remains to be clarified.

Adult↗

Circulating cardiac troponin I in trauma patients without cardiac contusion.

OBJECTIVES: To describe the evolution and the diagnostic value of cardiac troponin I (cTnI) and to relate its concentrations with the indicators of injury in trauma patients. DESIGN: Prospective, observational study of 17 young, previously healthy, mechanically-ventilated patients during the early post-traumatic period in the Surgical ICU of a University Hospital. METHODS: Serial measurements of serum cTnI, total creatine kinase activity (CKtot) and its isoenzyme MB (CK-MB) (on admission, 12 h later, then daily for 7 days), clinical data and repeated electrocardiographic (ECG) and transesophageal echocardiographic (TEE) recordings. RESULTS: Rhabdomyolysis was observed in all the patients with a significant relationship between CK-MB and CKtot. Despite the fact that no patient demonstrated ECG or TEE signs of myocardial contusion, elevated serum levels of cTnI were observed in six patients (35%) without obvious dilutional interference. As compared with the others, these patients exhibited a more frequent arterial hypotension (83% vs 18%, p = 0.035), required greater volume expansion on day 1 (22,000 vs 8,500 ml, p = 0.027) and usually demonstrated early (83% vs 9%, p = 0.005) and late (66% vs 9%, p = 0.028) multiple organ dysfunction syndrome. CONCLUSIONS: Taking into account the high reported sensitivity and specificity of cTnI dosage, the present results suggest cTnI can play a role in the evaluation of indirect myocardial injury following traumatic shock.

Adult↗

Pharmacokinetics and absolute bioavailability of ciprofloxacin administered through a nasogastric tube with continuous enteral feeding to critically ill patients.

OBJECTIVE: To determine the pharmacokinetics and absolute bioavailability of ciprofloxacin in 12 critically ill patients receiving continuous enteral feeding. DESIGN: a prospective, cross-over study. SETTING: 12-bed surgical intensive care unit in a University Hospital. PATIENTS: 12 stable critically ill patients on mechanical ventilation and receiving continuous enteral feeding (Normoreal fibres) without diarrhea or excessive residual gastric contents ( < 200 ml/4 h). None had gastro-intestinal disease, renal insufficiency (estimated creatinine clearance > or = 50 ml/min) or was receiving medications that could interfere with ciprofloxacin absorption or metabolism. MEASUREMENTS AND MAIN RESULTS: The study was carried out after the fourth (steady state) b. i. d. intravenous (i. v.) 1-h infusion of 400 mg and the second b. i. d. nasogastric (NG) dose of 750 mg (crushed tablet in suspension). Plasma concentrations were measured by high-performance liquid chromatography. The median (range) peak concentration after i. v. infusion was 4.1 (1.5-7.4) mg/l, and that after NG administration was 2.3 (0.7-5.8) mg/l, occurring 1.25 (0.75-3.33) h after dosing. The median [range] areas under plasma concentration-time curves were similar for the two administration routes (10.3 [3.3-34.6] and 8.4 [3.6-53.4] for i.v. infusion and NG administration, respectively). Ciprofloxacin bioavailability ranges from 31 to 82 % (median, 44%). CONCLUSIONS: In tube-fed critically ill patients, a switch to the NG ciprofloxacin after initial i. v. therapy to simplify the treatment of severe infections is restricted to those for whom serial assessments of ciprofloxacin levels are routinely available.

Adult↗

Cefepime and amikacin synergy in vitro and in vivo against a ceftazidime-resistant strain of Enterobacter cloacae.

The activities of cefepime and amikacin alone or in combination against an isogenic pair of Enterobacter cloacae strains (wild type and stably derepressed, ceftazidime-resistant mutant) were compared using an experimental model of pneumonia in non-leucopenic rats. Animals were infected by administering 8.4 log10 cfu of E. cloacae intratracheally, and therapy was initiated 12 h later. At that time, the animals' lungs showed bilateral pneumonia and contained more than 7 log10 E. cloacae cfu/g tissue. Because rats eliminate amikacin and cefepime much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters of humans. In-vitro susceptibilities showed an inoculum effect with cefepime proportional to the bacterial titre against the two strains, but more pronounced with the stably derepressed mutant strain, whereas with bacterial concentrations of up to 7 log10 cfu/mL, no inoculum effect was observed with amikacin. In-vitro killing indicated that antibiotic combinations were synergic only at intermediate concentrations. At peak concentrations, the combination was merely as effective as amikacin alone. At trough concentrations, a non-significant trend towards the superiority of the combination over each antibiotic alone was noted. Moreover, cefepime was either bacteriostatic or permitted regrowth of the organisms in the range of antibiotic concentrations tested. Although each antibiotic alone failed to decrease bacterial counts in the lungs, regardless of the susceptibility of the strain used, the combination of both antibiotics was synergic and induced a significant decrease in the lung bacterial count 24 h after starting therapy when compared with tissue bacterial numbers in untreated animals or animals treated with either antibiotic alone. No resistant clones emerged during treatment with any of the antibiotic regimens studied.

Amikacin↗

Efficacies of cefepime, ceftazidime, and imipenem alone or in combination with amikacin in rats with experimental pneumonia due to ceftazidime-susceptible or -resistant Enterobacter cloacae strains.

The antibacterial activities of human regimens of cefepime, ceftazidime, and imipenem alone or in combination with amikacin against an isogenic pair of Enterobacter cloacae strains (wild type and its corresponding derepressed cephalosporinase mutant) were compared by using our nonlethal model of pneumonia with 180 immunocompetent rats. Compared with untreated animals, all beta-lactam-treated rats, except those inoculated with the mutant isolate and receiving ceftazidime, had significantly lower bacterial counts in their lungs 60 h after the onset of therapy. Although the combination of a beta-lactam and amikacin was more bactericidal than each corresponding antimicrobial agent alone, true synergy was noted only with cefepime and imipenem against the constitutive derepressed strain.

Amikacin↗

Cefepime and amikacin synergy against a cefotaxime-susceptible strain of Enterobacter cloacae in vitro and in vivo.

We developed an experimental model of pneumonia to evaluate the efficacy of new antibiotic regimens against Enterobacter cloacae. Rats were infected by administering 8.5 log10 cfu E. cloacae intratracheally, and therapy was initiated 24 h later. At that time, animals' lungs showed bilateral pneumonia containing more than 7 log10 cfu/g of tissue. Because rats eliminate amikacin and cefepime much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters in humans. Using this model, we compared the bactericidal activities of cefepime and amikacin alone or in combination against the same cefotaxime-susceptible E. cloacae strain. The MICs of cefepime and amikacin for this strain were 0.5 and 2 mg/L, respectively. In-vitro killing studies showed that antibiotic combinations were synergic only at intermediate concentrations. At peak concentrations, the combination was only as effective as amikacin alone. At trough concentrations, a non-significant trend towards the superiority of the combination over cefepime alone was found. In-vivo studies showed that each antibiotic alone failed to decrease bacterial counts in the lungs except at 6 h, whereas the combination of both antibiotics induced a significant decrease in the lung bacterial count 6, 12 and 24 h after the onset of therapy when compared with tissue bacterial numbers in untreated animals or animals treated with either antibiotic alone. In-vivo synergy between cefepime and amikacin was observed at the three time points studied. No resistant clones emerged during treatment with any of the antibiotic regimens studied.

Amikacin↗

Transgastric, pulsed Doppler echocardiographic determination of cardiac output.

OBJECTIVE: The aim of this study was to evaluate the accuracy of cardiac output measurement with transesophageal echocardiography (TEE) using a transgastric, pulsed Doppler method in acutely ill patients. DESIGN: Cardiac output was simultaneously measured by thermodilution (TD) and a transgastric, pulsed Doppler method. SETTING: The study was carried out in a surgical intensive care unit as part of the management protocol of the patients. PATIENTS: Thirty consecutive acutely ill patients with a Swan-Ganz catheter, mechanically ventilated, sedated and with a stable hemodynamic condition were included. MEASUREMENTS: Pulsed Doppler TEE was performed using a transgastric approach in order to obtain a long axis view of the left ventricle. Cardiac output was calculated from the left ventricular outflow tract diameter, the velocity time integral of the blood flow profile and heart rate. RESULTS: One patient was excluded because of the presence of aortic regurgitation and another, because of the impossibility of obtaining a transgastric view. Twenty-eight simultaneous measurements were performed in 28 patients. A clinically acceptable correlation and agreement were found between the two methods (Doppler cardiac output = 0.889 thermodilution cardiac output +0.74 l/min, r = 0.975, p <0.0001). CONCLUSION: Transgastric pulsed Doppler measurement across the left ventricular outflow tract with TEE is a very feasible and clinically acceptable method for cardiac output measurement in acutely ill patients.

Adult↗

Use of the coagulase gene typing method for detection of carriers of methicillin-resistant Staphylococcus aureus.

Strains of Staphylococcus aureus can be typed on the basis of the polymorphism of the coagulase gene. DNA fragments generated after amplification by polymerase chain reaction (PCR) of the variable region of this gene and digested with the restriction enzyme HaeIII can be compared by their restriction fragment length polymorphism (RFLP). Seventy-nine of 86 (91.8%) methicillin-resistant S. aureus (MRSA) strains isolated in various hospitals had a characteristic RFLP pattern. This pattern differed from those of 32 methicillin-susceptible S. aureus (MSSA). Only one MSSA shared with MRSA the same RFLP pattern. After modification, we applied this method to the rapid detection of MRSA from 255 nasal swabs from patients hospitalized in intensive care units. When screened by plating on Chapman agar, 55 of these samples contained MRSA, whereas 40/55 yielded the expected restriction profile after amplification by PCR. No DNA was amplified by PCR in 9/55 samples and restriction profiles were uninterpretable in six cases. When compared to culture, the positive and negative predictive values of the PCR test were 100% and 93%, respectively. The specificity was 100% and the sensitivity was 72.7%. Since control of spread of MRSA strains in hospitals is based in part on rapid isolation of carriers, this method which allows detection of epidemic MRSA in nasal swabs within a day could be helpful, though culture would still be necessary to confirm the result.

Bacterial Typing Techniques↗

Prospective, randomized trial of two antiseptic solutions for prevention of central venous or arterial catheter colonization and infection in intensive care unit patients.

OBJECTIVES: To compare the efficacy of a newly available antiseptic solution (composed of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzyl alcohol), with 10% povidone iodine, on the prevention of central venous or arterial catheter colonization and infection. DESIGN: Prospective, randomized clinical trial. SETTING: Surgical-trauma intensive care unit (ICU) in a university hospital. PATIENTS: All patients admitted to the ICU and requiring the insertion of a central venous and/or an arterial catheter from July 1, 1992 to October 31, 1993. INTERVENTIONS: Patients were randomly assigned to one of two groups according to the antiseptic solution used for insertion and catheter care. The same solution was used for skin disinfection from the time of catheter insertion to the time of removal of each catheter. MEASUREMENTS AND MAIN RESULTS: Catheter distal tips were quantitatively cultured when catheters were no longer necessary, if there was a suspicion of catheter-related infection, and routinely after 7 days of use for arterial catheters, or after 15 days of use for central venous catheters. The rate of significant catheter colonization (i.e., > or = 10(3) colony-forming units [cfu]/mL by quantitative culture), and catheter-related sepsis (as defined by sepsis abating following catheter removal per 1,000 catheter-days), were significantly lower in the chlorhexidine group (12 vs. 31 [relative risk 0.4, 95% confidence interval 0.1 to 0.9, p < .01] and 6 vs. 16 [relative risk 0.4, 95% confidence interval 0.1 to 1, p = 0.5], respectively). The rate of central venous catheter colonization and central venous catheter-related sepsis per 1,000 catheter-days were also significantly lower in the chlorhexidine group (8 vs. 31 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .03] and 5 vs. 19 [relative risk 0.3, 95% confidence interval 0.1 to 1, p = .02], respectively). Finally, the rate of arterial catheter colonization per 1,000 catheter-days was significantly lower in the chlorhexidine group (15 vs. 32 [relative risk 0.5, 95% confidence interval 0.1 to 1, p = .05]), whereas the rate of arterial catheter-related sepsis per 1,000 catheter-days was similar for the two study groups (8 in the chlorhexidine group vs. 10 in the povidone iodine group [relative risk 0.8, 95% confidence interval 0.1 to 2.2, p = .6]). The 0.25% chlorhexidine solution was superior to the 10% povidone iodine solution in preventing catheter colonizations and catheter-related sepsis due to Gram-positive bacteria (5 vs. 20 [p < .001], and 2 vs. 10 [p < .001], respectively), whereas the activity of the 0.25% chlorhexidine solution was nonsignificantly superior in preventing Gram-negative infections (7 vs. 4 [p = .5], and 4 vs. 2 [p = .8], respectively). CONCLUSIONS: The 4% alcohol-based solution of 0.25% chlorhexidine gluconate and 0.025% benzalkonium chloride was more effective than 10% povidone iodine for insertion site care of short-term central venous and arterial catheters. This effect appeared related to a more efficacious prevention of infections with Gram-positive bacteria.

Adult↗

Influence of experimental rat model of multiple organ dysfunction on cefepime and amikacin pharmacokinetics.

We adapted an experimental model of multiple organ dysfunction to study the alterations it induces in the pharmacology of cefepime and amikacin. The half-lives of both antibiotics were significantly prolonged because of nonsignificant enhancement of the volume of distribution and reduced renal elimination. In the presence of multiple organ dysfunction, the concentration of each antibiotic in the lungs, compared with that in the lungs of healthy controls, was significantly decreased, despite similar concentrations in plasma, indicating that the application of a standard antibiotic concentration in plasma could lead to underdosage in tissues during the initial days of therapy.

Amikacin↗

Contribution of bronchoalveolar lavage to the diagnosis of posttraumatic pulmonary fat embolism.

OBJECTIVE: To verify whether the determination of the percentage of cells recovered by bronchoalveolar lavage and containing fat inclusions is a useful diagnostic tool of posttraumatic pulmonary fat embolism. DESIGN: Prospective study. SETTING: Surgical Intensive Care Units in two university hospitals. PATIENTS: 56 successive trauma patients needing prolonged postinjury mechanical ventilation, including 4 with clinical definite fat embolism syndrome, 5 in whom the diagnosis had been clinically suspected but was impossible to confirm or exclude before bronchoscopy, and 47 with no clinical evidence of the syndrome. Control groups included 8 patients without previous trauma who developed ARDS and 6 healthy surgical patients. METHODS: Bronchoalveolar lavage was performed within the first post-traumatic 3 days in trauma patients, at the beginning of the pulmonary disease in non trauma ARDS patients and just after anesthesic induction in healthy ortopedic patients. The magnitude of lipid content in alveolar cells was compared with the clinical pattern of the pulmonary fat embolism syndrome retrospectively evaluated at the seventh day postinjury in trauma patients. RESULTS: All the patients with definite fat embolism syndrome had more than 70% of lavage cells containing fat droplets. The group of patients in whom the diagnosis of the fat embolism syndrome was suspected had percentages of fat cells above 30% in 4 out of 5 patients. A percentage of fat cells above 30% was only observed in 7 out of the 47 patients without clinical evidence of the syndrome. The percentage varied between 0% to 35% in the group of non trauma ARDS patients and between 0 to 5% in healthy surgical patients. CONCLUSION: Lipid inclusions in alveolar cells are common during traumatic and non-traumatic respiratory failure. Determination of the percentage of cells recovered by bronchoalveolar lavage and containing fat droplets may contribute to the diagnosis of the fat embolism syndrome in mechanically-ventilated trauma patients with respiratory failure provided that the significant threshold would be 30%.

Adult↗

Role of systemic inflammatory response syndrome and infection in the occurrence of early multiple organ dysfunction syndrome following severe trauma.

OBJECTIVE: To evaluate the role of infection and systemic inflammatory response syndrome (SIRS) on the occurrence of early posttraumatic MODS. DESIGN: Retrospective study. SETTING: University Teaching Hospital ICU. PATIENTS: 163 consecutive patients hospitalized for more than 48 hours following severe trauma. MEASUREMENTS AND MAIN RESULTS: The patients were classified into two groups in respect to the existence of MODS at day 2. There was 27 patients in the MODS group and 136 patients in the no MODS group. The two groups were similar with respect to age, sex ratio and Simplified Acute Physiology Score. The MODS group had a higher mortality (52 versus 7%), Injury Severity Score (45 +/- 14 versus 31 +/- 13), hypovolemic shock rate (74 versus 30%), massive volume replacement rate (59 versus 6%) and SIRS rate (81 versus 54%) than the no MODS group (P < 0.05). The rate of infection was similarly low in the MODS and no MODS group (4 versus 6% respectively). CONCLUSION: Early MODS is often associated with hypotension and massive volume administration but very rarely with infection, despite the high rate of SIRS.

Adult↗

Limited usefulness of urinary dipsticks to screen out catheter-associated bacteriuria in ICU patients.

The use of urinary dipsticks to screen out sterile urine specimens was investigated in catheterized ICU patients. During a three-month period, each urine sample quantitatively cultured was concurrently tested at the bedside with a dipstick. A total of 102 urine samples taken from 43 patients were analysed. Thirty-eight of them showed bacterial or yeast growths (incidence rate, 37%). The negative predictive value of the leukocyte esterase pad and/or the nitrate test pad to screen out sterile urine samples was 81%, indicating that dipsticks cannot routinely be proposed to select catheterized ICU patients for quantitative culture of urine.

Bacteria↗

Pulmonary artery catheterization in critically ill patients: a prospective analysis of outcome changes associated with catheter-prompted changes in therapy.

OBJECTIVE: To evaluate physician accuracy in predicting patients' hemodynamic profiles, associated morbidities, rates of change in therapy resulting from catheterization, and the outcome variations associated with such change before the insertion of a pulmonary artery catheter. DESIGN: Prospective, descriptive, cohort study with no interventions. SETTING: Medical intensive care unit (ICU) of a university hospital. PATIENTS: One hundred twelve catheterizations performed in 112 patients without acute myocardial infarction. In 43 cases, catheterizations were indicated because of circulatory shock that was unresponsive to two standard therapeutic measures. MEASUREMENTS AND MAIN RESULTS: Before catheterization, physicians were asked to predict the hemodynamic profile of the patients who were to be catheterized, and to provide a plan for therapy. After catheterization, each patient's chart was reviewed and compared with precatheterization predictions. Hemodynamic profiles were correctly predicted in only 56% of the cases. Information obtained from pulmonary artery catheters prompted changes in therapy in 58% of all cases and in 63% of patients in shock who were unresponsive to standard therapy. Modifications varied among hemodynamic profiles, from 33% (fluid overloaded) to 87% (hypovolemia). Complications occurred in 11 catheterizations, but only two complications required therapy (pneumothorax [n = 1] and one episode of arrhythmia). No systemic infection occurred, and all blood cultures sampled through catheters before the catheters were withdrawn were sterile. In the entire group of patients, those patients in whom catheterization induced a change in therapy and those patients in whom no change in therapy occurred had similar precatheterization characteristics and mortality rates. However, in the subgroup of patients in shock that was unresponsive to standard therapy, the mortality rate was significantly lower when the assessment of hemodynamic data led to a change in therapy (59% vs. 100%, p = .009), despite identical precatheterization characteristics. CONCLUSIONS: Prompted by assessment of pulmonary artery catheter measurements in patients with circulatory shock who were unresponsive to standard therapeutic measures, a change in therapy for these patients was associated with an improved prognosis, independent of other variables influencing outcome.

Adult↗