Dual chamber pacemaker implantation in dogs with atrioventricular block.

BACKGROUND: Pacemaker implantation is the treatment of choice for symptomatic bradyarrhythmias. In dogs, a single chamber system is commonly used. In human patients with high-grade 2nd- or 3rd-degree atrioventricular (AV) block, physiologic pacing is recommended, because it improves cardiac output, blood pressure, exercise tolerance, and quality of life. In dogs, this type of pacing is seldom used. HYPOTHESIS: The implantation of a dual chamber pacemaker in dogs with AV block is a feasible procedure for restoring AV synchrony. ANIMALS: Thirty-three privately owned dogs with high-grade 2nd- or 3rd-degree AV block were included. METHODS: Patient data of all dogs with AV block presented for pacemaker implantation between December 1997 and November 2004 were reviewed. RESULTS: Dual chamber pacemaker implantation with AV synchronous stimulation was successfully performed in 33/33 dogs (100%). In 9/33 (27%) major and in 12/33 (36%) minor complications were observed. Mean survival time for the patients discharged from hospital (n = 32) was 33.6 +/- 20.4 months (range, 3.9-83.5 months). CONCLUSION AND CLINICAL IMPORTANCE: Dual chamber pacing is a feasible procedure in dogs with 2nd- or 3rd-degree AV block and is not associated with a higher complication rate compared with single chamber pacemaker systems. A major advantage over ventricular demand pacemaker systems is the restoration of AV synchrony for a substantial period of time.

Monitoring industrial wastewater by online GC-MS with direct aqueous injection.

An online GC-MS-system for automated monitoring of crude wastewater at a complex chemical production site is presented. The modular system is, in principal, based on commercial equipment, but utilizes a special, two-stage injector, which consists of a splitless vaporization chamber on top of a PTV injector filled with Tenax. This set-up enables direct injection of wastewater. Almost 140 volatile and semi-volatile compounds are calibrated down to 1 mg L(-1), which is sufficient for analysis of the influent of the wastewater-treatment plant. Two instruments analyze alternately, every 20 min, and the instrument cycle time is 40 min. The quantitative results are transferred to a database which is connected to a process-control system. Depending on the nature and concentration of a compound, an alarm can be generated and the wastewater stream can be diverted into an "off spec tank" if necessary. The GC-MS-system operates quasi-continuously with a system availability >98%. Data quality is automatically controlled in each run and by daily analysis of a quality-control sample. The development of a novel stacked PTV-PTV injector design to expand the range of analytes to selected basic compounds is described.

Transvenous embolization of small patent ductus arteriosus with single detachable coils in dogs.

Transvenous embolization of small patent ductus arteriosus (PDA; < or = 4 mm) with a single detachable coil was attempted in 24 dogs (median age 5.7 months, range, 2.6-65.5 months; median body weight 5.5 kg, range, 1.5-30.0 kg). Angiographic imaging of the duct and pressure measurements were made before and after embolization. The minimal ductal diameter was 2.7 +/- 0.7 mm. In all dogs, a single coil was employed regardless of residual shunting. Ten dogs (PDA minimal diameter range, 1.5-2.2 mm) received a 5-mm coil, and 14 dogs (PDA minimal diameter range, 2.9-3.6 mm) received a 8-mm coil. After coil embolization the angiographic shunt grade decreased significantly (n = 20, P < .001). Residual shunts were assessed by angiography 15 minutes after and by Doppler echocardiography 1-3 days and 3 months after the intervention. In the dogs treated with the 5-mm coils the residual shunt rate was low (0%, 10%, and 0% for angiography and Doppler echocardiography at 1-3 days and 3 months, respectively), in contrast to the dogs treated with the 8-mm coils (91%, 79%, and 67% for angiography and Doppler echocardiography at 1-3 days and 3 months, respectively). After 3 months, no residual murmur was found in dogs treated with the 5-mm coils (0/7), in contrast to murmurs in 5 of 12 (42%) dogs treated with the 8-mm coils. Despite incomplete closure in these dogs, volume loading of the left heart decreased in all dogs. Pulmonic or aortic coil embolism did not occur. Analysis of initial results shows that single detachable coil embolization is possible in all dogs with a small PDA (< or = 4 mm), but only very small PDA (< or = 2.5) could be treated effectively, and for the moderate PDA (2.6-4.0 mm) longer coils or multiple coils may be necessary to achieve complete occlusion.

Endogenous ouabain and its binding globulin: effects of physical exercise and study on the globulin's tissue distribution.

Ouabain, that has been isolated from bovine adrenals and hypothalamus, is a new cardiotonic steroid hormone, which is either synthesized in the adrenals or stored there after it has absorbed from the diet. Little is known in vivo which events may lead to the release of ouabain into blood. Moreover, a binding protein for cardiotonic steroids exists in blood, which binds cardiac glycosides with high affinity. It may affect the action of endogenous ouabain on heart and circulation, but the physiological function of this protein is unclear. To realize, which physiological stimuli in vivo may affect blood concentrations of endogenous ouabain and which function the cardiotonic binding protein may have in modulating ouabain effects, the effect of physical exercise on endogenous ouabain was studied and the tissue distribution of its binding protein was investigated. We found that endogenous ouabain changes rapidly in blood upon physical exercise and behaves like expected for a hormone of circulation. The cardiotonic steroid binding globulin shows the highest concentration in the kidney, which suggests that sodium pumps of the kidney are protected against its inhibition by ouabain which would lead not only to natriuresis but also to a deleterious loss of glucose, amino acids and phosphate.

[Feasibility of sonography in the diagnosis of congenital heart diseases in dogs]. / Möglichkeiten der Sonographie in der Diagnostik häufiger Herzmissbildungen beim Hund.

In ultrasound examination of the heart it is useful to combine the following techniques: echocardiography (in 2D and M-mode) gives information about morphology and motion of the heart. By using Doppler echocardiography (black and white or preferably colour) it is possible to evaluate bloodstreams and with contrast echocardiography shunts in the heart can be demonstrated. In our study (1994-1996) the following congenital heart defects were the most common in dogs: subaortic stenosis (SAS, 41%), pulmonic stenosis (PS, 19%), patent ductus arteriosus (PDA, 11%) and the combination of subaortic stenosis with pulmonic stenosis (11%). Echocardiography allows the morphologic evaluation of the primary defect in detail, for example the differentiation between aortic valve stenosis and subaortic stenosis. However the exact identification of the patent ductus arterious and of the morphology in pulmonic stenosis can remain difficult, especially in patients showing dyspnoe. In heart sonography quantitative measurements are available to graduate the defects, but guidelines for these measurements are not yet defined. The demonstration of secondary and combined defects, which are important for therapy is easily possible with heart ultrasound examination. Secondary insufficiencies are often seen at the mitral valve because of primary subaortic stenosis or patent ductus arteriosus and at the tricuspid valve because of pulmonic stenosis. For differentiation of combined heart defects (SAS with PS; SAS with PDA; PS with atrium septum defect) heart ultrasound is extremely valuable.

Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane (18F-MEM): a potential radioligand for mapping the NMDA-receptor complex.

The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that 19F-MEM is a moderate NMDA receptor channel blocker. A procedure for the routine preparation of the 18F-labelled analog 18F-MEM has been developed using a two-step reaction sequence. This involves the no-carrier-added nucleophilic radiofluorination of 1-[N-(tert-butyloxy)carbamoyl]-3-(toluenesulfonyloxy)methyl- 5-methyl-adamantane and the subsequent cleavage of the BOC-protecting group using aqueous HCI. The 18F-MEM was obtained in 22 +/- 7% radiochemical yield (decay-corrected to EOB) in a total synthesis time including HPLC purification of 90 min. A biodistribution study after i.v. injection of 18F-MEM in mice showed a fast clearance of radioactivity from blood and relatively high initial uptake in the kidney and in the lung, which gradually decreased with time. The brain uptake was high (up to 3.6% ID/g, 60 min postinjection) with increasing brain-blood ratios: 2.40, 5.10, 6.33, and 9.27 at 5, 30, 60, and 120 min, respectively. The regional accumulation of the radioactivity in the mouse brain was consistent with the known distribution of the PCP recognition site. Preliminary PET evaluation of the radiotracer in a rhesus monkey demonstrated good uptake and prolonged retention in the brain, with a plateau from 35 min onwards p.i. in the NMDA receptor-rich regions (frontal cortex, striata, and temporal cortex). Delineation of the hippocampus, a region known to contain a high density of NMDA receptors, was not possible owing to the resolution of the PET tomograph. The regional brain uptake of 18F-MEM was changed by memantine and by a pharmacological dose of (+)-MK-801, indicating competition for the same binding sites. In a preliminary experiment, haloperidol, a dopamine D2 and sigma receptor antagonist, decreased the binding of 18F-MEM from the brain regions examined, suggesting that binding was also occurring to the sigma recognition sites.

National epidemiology of mycoses survey: a multicenter study of strain variation and antifungal susceptibility among isolates of Candida species.

The National Epidemiology of Mycoses Survey (NEMIS) involves six academic centers studying fungal infections in surgical and neonatal intensive care unit (ICU) patients. We studied variation in species and strain distribution and anti-fungal susceptibility of 408 isolates of Candida spp. Candida spp. were isolated from blood, other normally sterile site cultures, abscesses, wounds, catheters, and tissue biopsies of 141 patients hospitalized in the surgical (107 patients) and neonatal (34 patients) ICUs of medical centers located in Oregon, Iowa, California, Texas, Georgia, and New York. Isolates were also obtained from selected colonized patients (16 patients) and the hands of health care workers (27 individuals). DNA typing was performed using pulsed field gel electrophoresis, and antifungal susceptibility to amphotericin B, 5-fluorocytosine, fluconazole, and itraconazole was determined using National Committee for Clinical Laboratory Standards (NCCLS) methods. Important variation in susceptibility to itraconazole and fluconazole was noted: MICs of itraconazole ranged from 0.25 microgram/mL (MIC90) in Texas to 2.0 micrograms/mL (MIC90) in New York. Similarly, the MIC90 for fluconazole was higher for isolates from New York (64 micrograms/mL) compared to the other sites (8-16 micrograms/mL). In general, DNA typing revealed patient-unique strains; however, there were 13 instances of possible cross-infection noted in 5 of the medical centers. Notably, 9 of the 13 clusters involved species of Candida other than C. albicans. Potential transmission from patient-to-patient (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis) and health care worker-to-patient (C. albicans, C. parapsilosis, C. krusei) was noted in both surgical ICU and neonatal ICU settings. These data provide further insight into the epidemiology of nosocomial candidiasis in the ICU setting.

Effects of the substituted (S)-3-phenylpiperidine (-)-OSU6162 on PET measurements in subhuman primates: evidence for tone-dependent normalization of striatal dopaminergic activity.

(-)-OSU6162 is a substituted (S)-3-phenylpiperidine derivative which exhibits some affinity to the dopamine D2 receptor family. In vivo, the compound displays a unique normalizing profile on psychomotor activity by an intriguing mixture of stimulatory and inhibitory properties. In the present investigation, some of the effects of (-)-OSU6162 on central dopaminergic function were studied by positron emission tomography (PET) and L-[11C]DOPA in anaesthetized female rhesus monkeys. (-)-OSU6162 displayed a dopaminergic tone-dependent effect with a reduction in the striatal L-[11C]DOPA influx rate in monkeys with high baseline values and an increased striatal L-[11C]DOPA influx rate in animals with low baseline values. Infusion of (-)-OSU6162 for a whole day resulted in a stable effect with no evidence of tolerance. (-)-OSU6162 also stabilized dopaminergic function by attenuating the upregulation of the striatal L-[11C]DOPA influx rate which has previously been shown to occur following 6R-BH4 or 6R-BH4 + L-tyrosine infusions. This "Protean" effect of (-)-OSU6162 on the striatal dopaminergic function corresponds to previous behavioral observations in intact animals and demonstrates a true functional correlation to the measures obtained with L-[11C]DOPA and PET. The normalizing and stabilizing profile of (-)-OSU6162 should be of value in treating a variety of disorders where an underlying dysregulation or disruption of dopaminergic function can be assumed.

Reduction in tuberculin skin-test conversions among medical house staff associated with improved tuberculosis infection control practices.

OBJECTIVE: To assess the efficacy of an infection control program as measured by tuberculin skin-test (TST) conversion rates in medical house staff. DESIGN: Observational study. SETTING: University-based hospital in New York City serving a large indigent population. PARTICIPANTS: Medical house staff. INTERVENTIONS: TST conversions were measured every 6 months in medical house staff from June 1992 to June 1994. Compliance with the isolation policy was measured by identifying room locations 24 hours after admission of patients who had Mycobacterium tuberculosis recovered from respiratory specimens. RESULTS: The TST conversion rate decreased from 5.8 to 0, 2.3, and 0 per 100 person years of exposure in successive 6-month periods. The estimated annual TST conversion rate among interns fell from 7 per 100 person years in June 1992 to 0 per 100 person years in June 1993 and 0 per 100 person years in June 1994 (P < .029). The proportion of patients with pulmonary tuberculosis who were isolated in negative-pressure rooms increased from 38% to 75% over the study period (P < .01). CONCLUSION: Development of a multifaceted infection control program can decrease the risk of nosocomial tuberculosis infection in medical house staff.

Synthesis of [11C-methyl]-(-)-OSU6162, its regional brain distribution and some pharmacological effects of (-)-OSU6162 on the dopaminergic system studied in the rhesus monkey by positron emission tomography.

The labelling of the presynaptic dopamine receptor antagonist (-)-OSU6162, ((S)-(-)-3-(3-(methylsulfonyl)phenyl)-1-propylpiperidine) was performed by an alkylation with [11C]methyl iodide of the thio anion (-)-OSU1281, followed by a selective oxidation to the corresponding methyl sulfone, [11C-methyl]-(-)-OSU6162. The total radiochemical yield calculated from the produced [11C]carbon dioxide to final product was about 25% and the time of synthesis was in the range of 40 min from end of bombardment. The synthesis of the precursor, (-)-OSU1281, was performed from (-)-3PPP in a three-step synthesis. The regional brain distribution of (-)-OSU6162 radiolabelled with 11C was studied in rhesus monkeys by means of positron emission tomography, PET. [11C-Methyl]-(-)-OSU6162 was rapidly and uniformly distributed to gray matters of the brain, and no decrease of radioactivity uptake in the brain was seen after pretreatment with 1 to 3 mg/kg/h of (-)-OSU6162. The effect of doses of 1 to 3 mg/kg/h of (-)-OSU6162 on the dopamine binding was studied by PET using [11C-methyl]raclopride. Radioactivity in the striatum was significantly and dose-dependently decreased by (-)-OSU6162 (r = 0.88), supporting competition with dopamine for selective binding to dopamine receptors.

Antibiotic susceptibility of multiply resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis, including candidates for transplantation.

Chronic lung disease caused by antibiotic-resistant Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is difficult to treat, especially in those who are lung transplantation candidates. Analysis of antibiotic susceptibility and synergy studies of 1,296 isolates revealed that 172 (13.3%) were multiply resistant (i.e., resistant to two or more classes of anti-Pseudomonas agents). beta-Lactam agents (including imipenem and aztreonam) or aminoglycosides inhibited only 11% of the multiply resistant strains, while ciprofloxacin inhibited 34%. High concentrations of tobramycin and gentamicin (200 micrograms/mL), achievable by aerosol administration, inhibited 95% of isolates and overwhelmed permeability-resistance mechanisms. Antimicrobial pairs tested in checkerboard dilutions of clinically achievable drug concentrations inhibited 75% of the multiply resistant strains. On average, three additive and 2.4 synergistic pairs of antimicrobial agents had activity per strain. Transplantation candidates were older than nontransplantation candidates (P = .034), and isolates from transplantation candidates were less likely to be inhibited by antibiotic combinations (P < .001). Administration of aerosolized aminoglycosides and synergy testing of antimicrobial combinations may represent viable therapeutic options for patients with CF.

Receptor imaging technique with 11C-labeled receptor ligands in living brain slices: its application to time-resolved imaging and saturation analysis of benzodiazepine receptor using [11C]Ro15-1788.

Recently we developed a novel imaging technique using positron emitter-labeled compounds as probes and a storage phosphor screen as a detector. This approach makes it possible to follow a variety of biochemical processes with spatial information in living brain slices. Further technical development is reported here in terms of time-resolved imaging and receptor characterization in a real equilibrium state. The method was validated by use of [11C]Ro15-1788, a benzodiazepine receptor antagonist. Fresh brain slices were incubated with [11C]Ro15-1788 in oxygenated Krebs-Ringer solution at 37 degrees C, in a specially designed chamber. By placing the chamber on a storage phosphor screen, we could obtain two-dimensional images of radioactivity in the slices. Time-resolved imaging was made at 5 min intervals, revealing that it took 60 min to reach equilibrium binding. The dissociation process was observed by adding an excess amount of unlabeled Ro15-1788 to the chamber, 25 min was required for the full dissociation. In the equilibrium state, i.e. in the presence of free radio-ligand, Scatchard plot analysis was performed on the cerebral cortex (Kd = 7.4 nM, Bmax = 146 fmol/mg tissue) and striatum (Kd = 7.5 nM, Bmax = 107 fmol/mg tissue), suggesting the presence of a single component of binding site in these two regions. The present method, for the first time, made it possible to study a ligand-receptor interaction in living brain slices with temporal and spatial resolutions. This technique should prove useful for studies of receptor function under physiological conditions.

Safety of cefepime: a new extended-spectrum parenteral cephalosporin.

The purpose of this study was to compare the safety profile of cefepime, a new extended-spectrum, fourth-generation cephalosporin used to treat mild-to-severe bacterial infections, with that of ceftazidime. A total of 2,032 patients enrolled in North American and European cefepime trials were analyzed. The study population spanned adolescence to the elderly (15-100 years); the median age was 62 years. Cefepime was compared with ceftazidime (1,456 patients), a third-generation cephalosporin. Cefepime dosing was 1-4 g/day (0.5-2.0 g twice daily) for adults; ceftazidime dosing was 1-6 g/day (0.5 g every 12 hours to 2.0 g every 8 hours). A limited number of cefepime-treated patients received 2 g every 8 hours. The median length of dosing for both cefepime and ceftazidime was 7 days. In randomized trials in which cefepime (2,032 patients) was compared with ceftazidime (1,456 patients), analysis of comparative data indicated that adverse events of probable or unknown relation to study drugs were observed in 13.8% of cefepime patients and 15.6% of ceftazidime patients. The most commonly observed adverse event for cefepime was headache (2.4%), followed by nausea (1.8%), rash (1.8%), and diarrhea (1.7%). For ceftazidime, the most commonly observed adverse event was diarrhea (3.2%), followed by headache (2.5%), nausea (2.1%), rash (1.9%), and constipation (1.5%). The incidence of positive Coombs' test was higher in high-dose cefepime recipients than in ceftazidime recipients (14.5% vs 8.7%; p = 0.043), although there was no evidence of hemolysis in either treatment group. Coadministration of analgesics, diuretics, and anticoagulants did not increase incidence of adverse events associated with study-drug therapy. Adverse renal and hematologic events, as well as anaphylaxis and death, were rare in both groups. In the comparative trials with cefepime, anaphylaxis was reported in no patients receiving cefepime and in one patient receiving ceftazidime. None of the three seizures reported in patients receiving cefepime and one of six seizures in patients receiving ceftazidime were of probable or possible relationship to the study drugs. None of the 12 cases of gastrointestinal hemorrhage reported in cefepime patients or five cases reported in ceftazidime patients were judged to be related to treatment drug. Tolerance for intravenous administration in both treatment groups was similar. Cefepime did not effect any significant or unusual allergic, hematologic, gastrointestinal, neurologic, or renal toxicity when administered to patients with mild-to-severe infections, including those receiving concomitant medications. The safety profile of cefepime is excellent and comparable to that of ceftazidime and those reported for other cephalosporins.

[Doppler echocardiography of heart valve defects in the dog]. / Doppler-echokardiographische Darstellung von Herzklappenvitien beim Hund.

In the diagnosis of heart diseases the Doppler echocardiography makes it possible to distinguish physiological and pathological blood flow and thus to prove and judge valve defects in a noninvasive way. The color Doppler gives a survey about place and direction of the streams. The exact analysis and quantification of the stream speed results from the spectral Doppler. Valve stenosis is characterized by a flow acceleration on the level of the stenosis. The increased speed is used for estimation of the severity of the stenosis. Valve insufficiency is recognized by a reflux of blood to the ventricle or atrium, respectively. The extent of the insufficiency can be evaluated semiquantitatively.

[Echocardiographic reference ranges of sedated cats]. / Echokardiographische Referenzbereiche von sedierten Katzen.

The aim of this study was to get echocardiographic values of sedated healthy cats of the race European short hair for further reference. After the preliminary examinations checking on the state of health (anamnesis, general and special clinical examinations, ECG, X-ray of thorax and preparation of selected laboratory parameters), 74 sedated animals and additionally 33 cats without sedation were echocardiographically measured. For sedatives we used ketamine hydrochloride and xylazine in order to minimize defending movements of the animals and to reduce the heart rate, which facilitated the echocardiographical measurements. The covariance analysis of the measured values showed a statistically significant dependence on the weight. This did not hold for the two calculated values of the fractional shortening (FS) and the quotient of left atrium and aorta (LA/Ao), where the weight-dependence of each component was compensated by the calculation of the quotient. All stated weight-dependent reference values refer to an average bodyweight of 4.0 kg. A dependence on the age did not show in the covariance analysis. Due to the sedation, the diameter of the left atrium (LA) and the diameter of the left ventricular lumen in the diastole (LVDd) as well as the fractional shortening decreased significantly.

Laboratory assessment of antibacterial activity of zwitterionic 7-methoxyimino cephalosporins.

Zwitterionic 7-methoxyimino cephalosporins (cefpirome, cefepime, cefclidin, DQ2556, FK037 and SCE2787) possess a variable substitution at C3 which contains a quarternary nitrogen. These cephalosporins display low affinities for Class I beta-lactamase and rapid penetration through the outer membrane of Gram-negative bacilli, so that an increased number of periplasmic beta-lactam molecules interact with PBP's per unit of time. As a consequence, the new zitterionic compounds remain active against some, but not all, ceftazidime-resistant Enterobacteriaceae producing high levels of Class I beta-lactamase or Bush type 2b beta-lactamases. Antipseudomonas activities are generally similar to that of ceftazidime except that cefclidin is more active. The new zwitterionic compounds, especially cefpirome and FK037, express greater antistaphylococcal potency than does ceftazidime. A variety of animal models including meningitis and endocarditis have confirmed the potential of these compounds in-vivo. On the basis of structural and antibacterial characteristics, the expression 'forth generation' is acceptable to describe the zwitterionic 7-methoxyimino cephalosporins.

Postantibiotic effect of ceftibuten on respiratory pathogens.

The postantibiotic effect (PAE) of ceftibuten, a novel beta-lactamase-stable cephem, was determined for Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The ceftibuten PAE after a 2-hour exposure to 2 micrograms/ml (4 x minimum inhibitory concentration) for S. pyogenes was 2.7 to > 10 hours. The PAE for S. pneumoniae after a 2-hour exposure to 15 micrograms/ml, concentrations that are achieved in man after usual therapeutic doses, was 1.1 to 3.4 hours and the PAE for H. influenzae was 1 to 1.1 hours. M. catarrhalis had a PAE of 1.5 to 1.8 hours after exposure to 15 micrograms/ml of ceftibuten. The ceftibuten PAE was not affected by serum. The ceftibuten PAE was prolonged by exposure to a sub-minimum inhibitory concentration concentration of ceftibuten as would occur in the clinical situation. The PAE of ceftibuten was not affected by the copresence of erythromycin as would occur when treating infections in which atypical organisms are suspected. There was no correlation between bacterial reduction in colony-forming units and the duration of PAE. A level of 6 micrograms/ml of ceftibuten had a similar bacterial killing activity compared with a 6-hour exposure to 15 micrograms/ml of ceftibuten against S. pneumoniae, H. influenzae and M. catarrhalis. This study suggests that ceftibuten can be administered orally, once daily in an adult dose of 400 mg or a pediatric dose of 9 mg/kg, to treat respiratory infections caused by the most common pathogens.

Ceftibuten: minimal inhibitory concentrations, postantibiotic effect and beta-lactamase stability--a rationale for dosing programs.

Ceftibuten, a new orally absorbed cephalosporin with a novel side chain, has broad in vitro activity against most of the important respiratory pathogens including Streptococcus pneumoniae and both beta-lactamase-negative and beta-lactamase-positive Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. Furthermore it has high activity against Enterobacteriaceae, which contain classic TEM-1 beta-lactamases and those containing the new extended spectrum beta-lactamases, which hydrolyze parenteral third generation cephalosporins. Studies have shown that ceftibuten has a postantibiotic effect comparable to that of other beta-lactams against S. pneumoniae, H. influenzae and M. catarrhalis. Blood levels achieved after a single 400-mg dose given once daily or 9 mg/kg/day taken once daily for children yield blood levels and postantibiotic inhibition for the majority of a dosing period. The in vitro and pharmacokinetic data can be correlated to provide reasonable dosing programs for the new oral cephalosporins.

Emergence and mechanisms of bacterial resistance in surgical infections.

Antimicrobial resistance is commonplace among bacteria involved in surgical infections, including Staphylococcus aureus, enterococci, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Bacteroides species. Resistance traits can be encoded on chromosomes or transmissible plasmids. The basic mechanisms of resistance are alteration of drug target, prevention of drug access to target, and drug inactivation. Examples include alteration of penicillin-binding proteins in resistance to penicillinase-resistant penicillins, ribosomal binding site protection in tetracycline resistance, and beta-lactamase destruction of beta-lactam compounds. Resistance due to the many types of beta-lactamases that have thus far been identified is wide-spread among common pathogens; use of beta-lactam/beta-lactamase inhibitor combinations has proved effective as one means of counteracting such resistance. Contending with resistance involves appropriate use of available antimicrobials, development of novel agents or modification of existing agents, and measures to forestall emergence and spread of resistant organisms.