Changing trends in frequency and antimicrobial resistance of urinary pathogens in outpatient clinics and a hospital in Southern Israel, 1991–1995

In order to monitor changes in the frequency and antimicrobial resistance of urinary pathogens over several years, urinary cultures received from outpatient clinics and from a hospital during a period of one month each in 1991 and 1995 were analyzed at a clinical microbiology laboratory. In 1991 and 1995, 1366 and 1534 significant monomicrobic cultures respectively were reviewed. The frequency ofEscherichia coli dropped significantly in the outpatient clinics from 70.5% to 61.2% (p<0.0001). The frequency ofProteus mirabilis, Morganella morganii, Pseudomonas aeruginosa and other gram-negative bacteria also decreased, but the frequency ofKlebsiella spp. andEnterobacter spp. increased from 2.6% to 5.8% (p<0.0001). In the hospital, the frequency ofEnterobacter spp. (p<0.04),Escherichia coli andMorganella morganii declined from 1991 to 1995, whereas the frequency ofPseudomonas aeruginosa (p=0.001),Acinetobacter spp. (p<0.05),Klebsiella spp.,Proteus mirabilis and other gram-negative rods increased considerably. The frequency of gram-positive aerobic bacteria rose markedly in outpatient specimens from 6.1% to 13.5% (p<0.0001), while a decline from 14.4% to 9.3% was noted in hospital specimens (p<0.02). A significant rise in the resistance ofEscherichia coli to gentamicin and ciprofloxacin (p<0.0001) was detected in outpatient isoates. In the hospital, gram-negative urinary pathogens demonstrated increased resistance to ampicillin (p=0.042), cefuroxime (p=0.005), gentamicin (p=0.002) and ciprofloxacin (p<0.0001) during the study period. The changing etiology of urinary tract infections and the increasing resistance of organisms indicate that periodic monitoring and possibly also modification of empirical therapy are required.     

Pharmacokinetic dosing of aminoglycosides: a controlled trial

PURPOSE: To evaluate whether individualized pharmacokinetic dosing of aminoglycosides can reduce nephrotoxicity and improve the outcome of patients with gram-negative sepsis. METHODS: We conducted a prospective controlled trial at a tertiary care university hospital. Eighty-one patients with suspected or documented gram-negative infections were enrolled. All were treated with either gentamicin or amikacin, according to clinical judgement. Patients were allocated to one of two groups based on the last digit (odd/even) of their identification number. In the study group (pharmacokinetic dosing) of 43 patients, plasma aminoglycoside levels were determined 1 hour after initiation of drug infusion and 8 to 16 hours later to estimate the elimination half-life and volume of distribution, from which the subsequent dosage schedule was calculated. Target peak plasma levels were 20 microg/mL for gentamicin and 60 microg/mL for amikacin. Target trough levels were <1 microg/mL for both drugs. The control group (fixed once-daily dosing) consisted of 38 patients who were prescribed single daily doses of gentamicin or amikacin. The primary endpoints were renal toxicity (> or = 25% increase in serum creatinine level or a serum creatinine level > or = 1.4 mg/dL) and 28-day mortality. RESULTS: The two study groups were similar in age, sex, indications for therapy, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and clinical assessment at baseline. Although the pharmacokinetic group received significantly greater doses of aminoglycosides than did the once-daily group, the incidence of nephrotoxicity was significantly lower in the pharmacokinetic group (5% [2/43] vs. 21% [8/38], P = 0.03). There was no statistically significant difference in 28-day mortality (27% [12/43] vs. 22% [8/38], P = 0.3). CONCLUSION: These results suggest that individualized pharmacokinetic dosing of aminoglycosides reduces the incidence of nephrotoxicity and allows the use of greater doses of aminoglycosides.     

Septic arthritis due to bacteroides fragilis after pilonidal sinus resection in a patient with rheumatoid arthritis

Summary Bacteroides fragilis is a rare cause of septic arthritis. Most patients with B.fragilis septic arthritis have a chronic joint disease, particularly rheumatoid arthritis, and sources of infection are lesions of the gastrointestinal tract and the skin. We report a 69-year-old male, who developed B.fragilis septic arthritis after pilonidal sinus resection. High level of suspicion of development B.fragilis septic arthritis must be present in patients with chronic joint disease in whom gastrointestinal or skin surgery was previously performed.     

Incidence and clinical significance of bacteremia and sepsis among cardiac patients treated with intra-aortic balloon counterpulsation pump

In this prospective study, a significant incidence of fever (47%), true bacteremia (15%), and sepsis (12%), were found in 60 cardiac patients treated with an intra-aortic balloon counterpulsation pump. The benefit of antibiotic prophylaxis in this setting should therefore be evaluated.     

Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC_0–24,ss), the steady-state maximum concentration of the drug in plasma (C_max,ss), and the steady-state concentration of the drug in plasma at 24 h (C_24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01637922","term_id":"NCT01637922"}}NCT01637922.)     

Inhibition of superoxide production in human neutrophils by combinations of heparin and thrombolytic agents.

OBJECTIVE--To investigate the effect of heparin and thrombolytic agents on superoxide generation by human neutrophils, as inhibition of superoxide production may have a role in reducing ischaemia and reperfusion injury. METHODS--Neutrophil superoxide production stimulated by phorbol myristate acetate (PMA), opsonised zymosan, or formyl methionyl leucyl phenylalanine (FMLP) was measured as the superoxide dismutase inhibitable reduction of acetyl ferricytochrome c by a microtitre plate technique. RESULTS--Heparin, at concentrations of 0.5-500 U/ml, caused a gradual inhibition of superoxide production stimulated by PMA, opsonised zymosan, or FMLP. Tissue plasminogen activator was more potent than heparin in inhibiting superoxide production induced by opsonised zymosan or FMLP, but it did not affect the activity stimulated by PMA. Streptokinase or urokinase had no effect on superoxide production. When heparin was used in combination with tissue plasminogen activator, streptokinase, or urokinase at their therapeutic concentrations there was a significant inhibition of superoxide generation (70%, 30%, and 25%, respectively). The therapeutic concentrations of tissue plasminogen activator alone caused a reduction of 40% of neutrophil superoxide production. When tissue plasminogen activator and streptokinase were both added to neutrophils, however, a synergistic inhibition of 80% was achieved. CONCLUSIONS--The inhibition of super oxide generation by these drug combinations may explain the limited inflammatory response and reduction of reperfusion injury observed in patients receiving thrombolytic treatment.     

Urinary Tract Infections Caused by Multi-Drug Resistant <Emphasis Type="Italic">Proteus mirabilis</Emphasis>: Risk Factors and Clinical Outcomes

Background:   

Proteus mirabilis (PM) as well as other membersof the Enterobacteriaceae family are a leading cause ofinfectious diseases in both the community and acute caresettings. The prevalence of multi-drug resistant (MDR) bacterialisolates have increased in the last few years, affectingthe prognosis and survival of hospitalized patients. The aimof our study was to determine the risk factors and clinicaloutcomes of urinary tract infections (UTIs) caused by MDR PMin patients hospitalized in our institution.     

Effectiveness of a school-based intervention at changing preadolescents' tobacco use and attitudes

This study evaluated the effectiveness of a tobacco intervention on preadolescents' tobacco use and attitudes. A tobacco assessment questionnaire was distributed to seventh-grade students in May 1997 (N = 229) and 1999 (N = 230). During the 1998-1999 academic year, sixth-grade students at the intervention school received a tobacco intervention. Though not statistically significant, the number of smokers at the intervention school decreased from 43.2% to 31.1% after the intervention (p = .09). These students predicted less smoking in five years (29.6% to 19.8%, p = .078) and 20 years (28.4% to 13.2%, p = .004). Because of the difficulty in reducing smoking rates at the population level, the nonsignificant results can be viewed as a success rather than a setback. When faced with increasing use trends, an intervention can at least hope to achieve a decrease or slow the rate of growth, and the program succeeded in that respect. School-based interventions can effectively influence preadolescent' attitudes concerning tobacco use. Future programs should begin earlier and be reinforced yearly.