Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study.

We describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Patients (n = 1482) in 12 countries from an observational study of BSI caused by ESBL-E or CPE were included. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ß-lactam/ß-lactamase inhibitors (BLBLIs) or carbapenems, targeted use of BLBLIs for ESBL-E and use of targeted combination therapy for CPE. Compared with Spain, BLBLI use for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.25) and Turkey (aOR 2.09, 95% CI 1.14-3.81). Empirical carbapenem use was more likely in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89, 95% CI 1.05-3.39) and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLIs for ESBL-E was more likely in Italian sites. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. Better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.

The emerging threat of multidrug-resistant Gram-negative bacteria in urology.

Antibiotic resistance in Gram-negative uropathogens is a major global concern. Worldwide, the prevalence of Enterobacteriaceae that produce extended-spectrum ß-lactamase or carbapenemase enzymes continues to increase at alarming rates. Likewise, resistance to other antimicrobial agents including aminoglycosides, sulphonamides and fluoroquinolones is also escalating rapidly. Bacterial resistance has major implications for urological practice, particularly in relation to catheter-associated urinary tract infections (UTIs) and infectious complications following transrectal-ultrasonography-guided biopsy of the prostate or urological surgery. Although some new drugs with activity against Gram-negative bacteria with highly resistant phenotypes will become available in the near future, the existence of a single agent with activity against the great diversity of resistance is unlikely. Responding to the challenges of Gram-negative resistance will require a multifaceted approach including considered use of current antimicrobial agents, improved diagnostics (including the rapid detection of resistance) and surveillance, better adherence to basic measures of infection prevention, development of new antibiotics and research into non-antibiotic treatment and preventive strategies.

The costs of childhood epilepsy in Italy: comparative findings from three health care settings.

PURPOSE: To determine the direct costs of epilepsy in a child neurology referral population, stratified by disease, duration, and severity, comparing three different health care settings [i.e., teaching or clinical research (CR) hospitals, general hospitals, and outpatient services]. METHODS: Patients were accepted if they had confirmed epilepsy and were resident in the center catchment area. Eligible subjects were grouped in the following categories: (a) newly diagnosed patients; (b) patients with epilepsy in remission; (c) patients with active non-drug-resistant epilepsy; and (d) those with drug-resistant epilepsy. Over a 12-month period, data regarding the consuming of all resources (i.e., consultations, tests, hospital admissions, drugs), were collected for each patient. Using the Italian National Health Service tariffs, the unit cost of each resource was calculated and indicated in Euros, the European currency. RESULTS: A total of 189 patients was enrolled by two teaching-CR hospitals, two general hospitals, and two outpatient services. The patients were evenly distributed across the four categories of epilepsy. The mean annual cost per person with epilepsy was 1,767 Euros. Drug-resistant epilepsy was the most expensive category (3,268 Euros) followed by newly diagnosed epilepsy (1,907 Euros), active non-drug-resistant epilepsy (1,112 Euros), and epilepsy in remission (844 Euros). Costs were generally highest in teaching-CR hospitals and lowest in outpatient services. Hospital services were the major cost in all epilepsy groups, followed by drugs. CONCLUSIONS: The cost of epilepsy in children and adolescents in Italy tends to vary significantly depending on the severity and duration of the disease Hospitals services and drugs are the major sources of costs. The setting of health care plays a significant role in the variation of the costs, even for patients in the same category of epilepsy.

Pharmacokinetics of meperidine in healthy volunteers after short- and long-term exposure to high altitude.

Increased numbers of erythrocytes have been shown ex vivo to increase meperidine uptake, and one of the major physiologic changes that occurs at high altitude is an increase in hematocrit and erythrocytes. A study was therefore conducted to evaluate the effects of high altitude on the pharmacokinetics of meperidine. Intramuscular doses (0.75 mg/kg) of meperidine were given to three groups of healthy volunteers (age range, 18-20 years): participants living at sea level (group L), those same participants the day after arrival at high altitude (4,360 m; group HA), and participants who had lived at high altitude for > or = 10 months (group HC). Blood samples were collected for 12 hours after drug administration. Meperidine was measured in whole blood, plasma, and plasma water. Elimination rate constant (lambda z) and clearance uncorrected for bioavailability (Cl/F) were significantly lower at high altitudes than at sea level in plasma (HA and HC) and in whole blood (HA only). Mean residence time (MRT) was significantly higher at high altitudes than at sea level in plasma (HA and HC) and in whole blood (HA only). Hematocrit was significantly increased at both time points at high altitude in comparison to values at sea level, and was also higher after a long-term stay at high altitude than after arrival at high altitude. Erythrocyte binding increased significantly from 41.3% at sea level to 43.8% at arrival at high altitude to 50.9% after a long-term stay at high altitude. The extent of protein binding tended to decrease with high altitude, but this decrease was not significant. Free concentrations of meperidine in plasma water measured 1, 2, and 4 hours after administration were significantly increased after 2 and 4 hours.

Urinary excretion of meperidine and normeperidine in man upon acute and chronic exposure to high altitude.

The urinary excretion of unchanged meperidine (M) varies with change of pH and metabolism. Since exposure of man to high altitude (H) may cause significant physiologic changes, we investigated its effects on the urinary excretion of M. The study was carried out in 3 groups of healthy, male volunteers (ages 18-20 years): at sea level (L), at 4360 m the day after arrival at H (HA), and at 4360 m in subjects residing for > 10 months at H (HC). Urine was collected for the periods of 0-4, 4-8, 8-12 and 12-24 h. Urinary pH was measured and the concentrations of M and normeperidine (N) were determined. The 24 h excretion of M and N was significantly decreased for L vs. HA and L vs. HC. Significance was also seen for the periods 0-4, 4-8 and 8-12 h. The ratio of amount excreted M/N for the 24 h period was highly significant for L vs. HA and L vs. HC. The urinary pH ranged from 5.3-5.9 for L, 5.9-7.0 for HA, and 5.1-5.7 for HC. The Fel (fraction of M eliminated in the unchanged form in urine) significantly decreased from L to HA and HC.

Management of extremely low-birth-weight infants.

Better health care of women during pregnancy and delivery, improvement in neonatal intensive therapy and technology have led to a decrease in neonatal mortality and morbidity and to lower limits of birth weight and gestational age for survival. This paper refers to the management protocol used in the Department of Perinatal Pathology of the Provincial Maternity Hospital of Milan for extremely low-birth-weight (ELBW) infants (birth weight < 1000 g). In this hospital, all newborn infants presenting evidence of life, irrespective of birth weight and gestational age, are resuscitated and transferred to the Neonatal Intensive Care Unit (NICU) for clinical management. After the introduction of this protocol the mortality rate of ELBW infants dropped from 71.4% in 1977-78 to 48% in 1987-88. In a group of 72 ELBW infants with a mean birth weight of 850 g and a mean gestational age of 27 weeks, 80% presented a normal outcome, 12% presented a mild neurological impairment and 8% were affected by severe cerebral palsy at the age of two years. The intact survival of a newborn infant of 450 g at birth is also reported.

Short and long term prognostic significance of neurological anomalies of the first year in very low birthweight infants.

The short and long term, prognostic significance of early neuromotor anomalies was assessed in infants with birthweight under 1500 g (VLBW infants), who have a high risk of developing cerebral palsy (CP) but who also have transient neurological anomalies. The series comprises 35 VLBW infants born between 1 January 1978 and 31 March 1980 with regular neurological follow-up until the second year of life: 10 with CP of varying severity and 25 without CP. The latter were examined in the first year of school by means of an age-specific method designed to elicit minor neurological dysfunctions (MND). Analysis of neuromotor development in the first year of life identified important grounds for clinical suspicion in the first semester of corrected age, especially on the basis of a global neurological assessment including optimal neurological items score at presumed term age and the combination of two or more major neurological signs in the first semester. The diagnosis of CP cannot be established until the 2nd semester of life, in 70% of cases by the end of the 3rd trimester. It rests on the following criteria: persistence of two or more major neurological signs (abnormalities of limb tone, axial tone and of movement), specific pathological pattern of limb tone, always associated with retarded postural control. Neurological examination at school age revealed a significantly higher frequency of MND in the VLBW children than in a group of normal controls. The quantity of MND correlated significantly with the severity and duration of the first year neurological anomalies but not with the obstetric and postnatal neurological risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurological and psychological development of low-risk preterm infants in the first year of life.

Twenty-four selected low-risk preterm and 10 full-term infants were followed in a prospective study of the evolution of neurological signs in the first year of life and to consider the prognostic value of transient neurological abnormalities in relation to learning disabilities at school age. We report the results of the assessments made during the first 12 months. The assessment at 3, 6, 9 and 12 months was made using the Amiel-Tison neurological schedule and the Griffiths developmental scale. A high percentage of our low-risk premature infants (69% of 37-34 weeks gestational age and 75% of 33-27 weeks gestational age group) showed transient neurological anomalies, whereas no major neurological sequelae, i.e., cerebral palsies or mental impairment, were found. Moreover, in our series, the syndrome of transient dystonia associated with low birth weight, already described by other authors in samples not selected for risk, was not observed. The psychological development of all our infants was within normal limits at every assessment. Nevertheless, a significantly decreased performance at the sixth month in both preterm groups, particularly in the group of low gestational age, was found, and its significance will be clarified by further follow-up studies of early school age.

A case of simultaneous interstitial bilateral pregnancy.

Twin pregnancies may present tubal involvement in the following cases: (1) simultaneous intra- and extrauterine pregnancy; (2) interstitial bilateral pregnancy (either simultaneous or not); (3) multiple pregnancy in the same tube; and (4) simultaneous interstitial and ovarian pregnancy. Interstitial bilateral pregnancy appears to be by far the rarest kind of tubal twin pregnancy, apparently only one case having been reported in the literature, and this referring to a nonsimultaneous pregnancy. A case is now reported that therefore appears to represent the first observation of simultaneous interstitial bilateral pregnancy.

Triplet pregnancy in a subfertile woman treated with clomiphene citrate.

A 26-year-old subfertile woman with a history of abortions at the 7-9th week was treated with Clomid, 50 mg for 5 days. A pregnancy resulted, which ended in the premature birth of a set of alive triplets that sex and blood-group determinations showed to be trizgotic. It is suggested that this production of a multiple ovulation in a woman with luteal deficiency be the result of excessive dosage of Clomid.