Predictors of Opioid Resistance: An Investigation in Cancer Pain.

Appropriate use of opioid analgesics according to the World Health Organization pain relief ladder has provided pain relief to many patients with cancer pain. However, a proportion of patients fail to achieve sufficient pain relief and develop opioid resistance. Individual risk factors may relate to opioid resistance. Therefore, we conducted a historical cohort study to identify risk factors for opioid resistance and to construct an index to predict it. We investigated salient factors at the time of opioid initiation in the medical records of 233 patients. The outcome was the achievement of stable pain at 14 days after opioid introduction. We identified factors contributing to opioid resistance by multivariate analysis (p < 0.05). We created a resistance score from the regression equation of the identified factors to predict opioid resistance. Forty-nine (21.0%) patients were opioid resistant without achieving the outcome. Age, neuropathic pain, and alkaline phosphatase were extracted as significant factors for opioid resistance (p < 0.05). A resistance score was created from these factors and classified into binary values, the sensitivity was 80.6% and the negative predictive value was 91.6%. The findings suggest that the resistance score could be a sensitive predictor of opioid resistance before opioid initiation.

Predictive Factors of Opioid-Induced Nausea in Cancer Patients.

Approximately 30% of patients experience nausea after initiation of opioid therapy, which can lead to poor quality of life. We aimed to identify risk factors for opioid-induced nausea at the initiation of opioid therapy by conducting a retrospective review of medical records of patients diagnosed by palliative care specialists with solid cancer and pain at the lesion site at Showa University Hospital between June 2005 and June 2011. The primary endpoint was the development of nausea grade ≥1 according to the Common Terminology Criteria for Adverse Events version 4.0 within 48 hours of initiation of opioid therapy. The median age of the 134 enrolled patients was 67.7 (range 28-95) years. Fifty-three percent were male and 44% had gastrointestinal cancer. Furthermore, 22.4% had opioid-induced nausea. Age (odds ratio (OR) 1.74; 95% confidence interval (CI), 1.13-2.69), edema (OR 5.83; 95% CI, 1.22-28.19), and gastrointestinal cancer (OR 2.61, 95% CI 1.07-6.36) were significantly associated with opioid-induced nausea. Prophylactic antiemetics were found to be ineffective.

Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli.

Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for blaCTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of blaCTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice.

Validation of Cefazolin as Initial Antibiotic for First Upper Urinary Tract Infection in Children.

To validate the policy of administering cefazolin (CEZ) as a first-line antibiotic to children who are hospitalized with their first febrile urinary tract infection (UTI), we evaluated microbial susceptibility to CEZ and the efficacy of CEZ. The 75 enrolled children with febrile UTI were initially treated with CEZ. Switching CEZ was not required in 84% of the patients. The median fever duration, prevalence of bacteremia, prevalence of UTI caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli, and median duration of hospitalization were significantly higher in the CEZ-ineffective group. The risks of vesicoureteral reflux, indication of operation, and renal scarring are not increased, even when CEZ is ineffective as a first-line antibiotic. CEZ is effective in more than 80% of pediatric patients with their first febrile UTI, but it should be switched to appropriate antibiotics considering sepsis or the ESBL-producing Enterobacteriaceae pathogen, when fever does not improve within 72 hours.