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BACKGROUND: Underutilization of vaccination programs remains a significant public health concern. Pharmacists serve as educators, facilitators, and in some jurisdictions, as administrators of vaccines. Though pharmacists have been involved with immunizations in various ways for many years, there has yet to be a systematic review assessing the impact of pharmacists as immunizers in these three roles. OBJECTIVE: To complete a systematic review of the literature on the impact of pharmacists as educators, facilitators, and administrators of vaccines on immunization rates. METHODS: We identified 2825 articles searching the following databases from inception until October 2015: PubMed, EMBASE, Cochrane Libraries, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts, Google Scholar. Grey literature was identified through use of the Canadian Agency for Drugs and Technology in Health "Grey Matters" search tool. Content from relevant journals and references of included studies were also searched. Inclusion criteria were clinical or epidemiologic studies in which pharmacists were involved in the immunization process. Studies were excluded if no comparator was reported. Two reviewers independently completed data extraction and bias assessments using standardized forms. RESULTS: Thirty-six studies were included in the review, 22 assessed the role of pharmacists as educators and/or facilitators and 14 assessed their role as administrators of vaccines. All studies reviewed found an increase in vaccine coverage when pharmacists were involved in the immunization process, regardless of role (educator, facilitator, administrator) or vaccine administered (e.g., influenza, pneumococcal), when compared to vaccine provision by traditional providers without pharmacist involvement. Limitations of the results include the large number of non-randomized trials and the heterogeneity between study designs. CONCLUSIONS: Pharmacist involvement in immunization, whether as educators, facilitators, or administrators of vaccines, resulted in increased uptake of immunizations. PROSPERO Registration: CRD42013005067.

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To investigate whether patients should be immunized immediately or delay immunization until after reconstitution of the immune system and whether a conjugate or polysaccharide vaccine results in a better immunologic response. Seventy-nine patients were randomly assigned, utilizing a two by two factorial design to receive immediate immunization or delay immunization. Baseline characteristics were similar for the four arms: 78% men, median age 41 years, median time since HIV diagnosis 0.3 years, median CD4 60 cells/mm(3) and median HIV viral load 5.02 log copies/mL. Results in favour of delayed immunization were observed for those serotypes showing a response. The proportional odds ratios for delayed versus immediate immunization were 0.341 (P = 0.04) and 0.204 (P = 0.004) at months 6 and 12, respectively. No differences in immunological response were observed between the two individual vaccines for the shared serotypes studied. HIV-infected adults produced a higher immunological response to pneumococcal vaccine after reconstitution of the immune system.

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BACKGROUND: Detailed pharmacokinetics to guide oseltamivir (Tamiflu®) dosing in morbidly obese patients is lacking. METHODS: The OPTIMO trial was a single-centre, non-randomized, open-label pharmacokinetic study of single-dose and steady-state oral oseltamivir phosphate and its carboxylate metabolite in healthy, morbidly obese [body mass index (BMI) >  40)] and healthy, non-obese (BMI  <  30) subjects. RESULTS: In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir oral clearance (CL/F) [840 (range 720-1640) L/h versus 580 (470-1800) L/h] was higher, the area under the curve from time zero to infinity (AUC(0-∞)) [89 (46-104) ng·h/mL versus 132 (42-160) ng·h/mL] was lower and the volume of distribution (V/F) [2320 (900-8210) L versus 1670 (700-7290) L] was unchanged. In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir carboxylate CL/F [22 (17-40) L/h versus 23 (12-33) L/h], AUC(0-∞) [3100 (1700-4100) ng·h/mL versus 3000 (2100-5900) ng·h/mL] and V/F [200 (130-370) L versus 260 (150-430) L] were similar. Similar results for oseltamivir and oseltamivir carboxylate CL/F, AUC0₋12 and V/F values were observed in the multiple-dose study. CONCLUSIONS: With single and multiple dosing, the systemic exposure to oseltamivir is decreased but that of oseltamivir carboxylate is largely unchanged. Based on these pharmacokinetic data, an oseltamivir dose adjustment for body weight would not be needed in morbidly obese individuals.

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Patients with human immunodeficiency virus (HIV) infection often suffer from persistent, painful ulcers that commonly occur on the soft palate, buccal mucosa, tonsillar area or tongue, which are referred to as aphthous ulcers. This paper reports the case in which pentoxifylline was successfully used to treat recurrent aphthous ulcers in an HIV patient.

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A 68-year-old man receiving long-term therapy with oral sustained-release theophylline 450 mg twice/day was admitted to the hospital after failing treatment with azithromycin for an acute exacerbation of obstructive lung disease. Peak serum theophylline concentration was 20 microg/ml (normal 10-20 microg/ml). Azithromycin was discontinued and the theophylline dosage reduced by 33%. The subsequent 80% decrease in serum theophylline to 4.6 microg/ml was unexpectedly large. Two rechallenges produced similar transient depressions of serum theophylline concentrations after withdrawal of azithromycin, suggesting an interaction. Withdrawal of azithromycin may leave an increased number of active enzyme sites available as the drug is cleared from the system. In some circumstances, it may be useful for pharmacokinetic interaction studies to continue measuring concentrations after the suspected interacting agent is stopped.

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OBJECTIVE: To underscore the need for caution when making dramatic changes in phenytoin dosing, and to report a possible ciprofloxacin interaction in which failure of seizure control led to inappropriately high phenytoin dosing and subsequent intoxication. CASE SUMMARY: A 61-year-old African-American man receiving long-term therapy with phenytoin 100 mg po tid for seizures secondary to a stroke was admitted for community-acquired pneumonia. His serum phenytoin concentration at admission was therapeutic at 12.6 micrograms/mL. Eight days after admission, ciprofloxacin 750 mg po bid was started for possible aspiration. Two days later he experienced a seizure; the serum phenytoin concentration was 2.5 micrograms/mL. In response to the 80% decline in phenytoin concentration, the dosage was gradually titrated upward to produce a serum concentration of 12.6 micrograms/mL. This eventually required a doubling of the original phenytoin dosage and he was discharged on 200 mg po tid. The patient subsequently developed severe ataxia and sustained a head injury for which he was seen again in the emergency department. Serum phenytoin concentration at that time was 42.8 micrograms/mL. Concentrations declined at a normal rate when phenytoin was withheld. CONCLUSIONS: It appears that a rapid decline in phenytoin concentration during the first admission was related to coadministration of ciprofloxacin, either through inhibition of absorption or induction of metabolism. In a conscientious effort to titrate phenytoin concentrations back to therapeutic values, the issue as to why this required such a dramatic change in dosage was ignored. Thus, in trying to prevent further seizures, the patient was unknowingly placed in jeopardy a second time when his usual dosage of phenytoin was doubled. As a result, phenytoin intoxication ensued after discharge when the ciprofloxacin was discontinued. This case illustrates a potentially dangerous interaction between ciprofloxacin and phenytoin, and it underscores the need to maintain a high index of clinical suspicion for drug interactions in any patient requiring a substantial change in drug dosage.

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Nursing home-acquired pneumonia (NHAP) is a diagnostic and therapeutic challenge, and antimicrobial therapy represents only 1 facet of the treatment of this disease. The nursing home population consists of a mixture of well, frail and dependent elderly. For some residents, supportive care may be the best therapeutic option. A variety of antimicrobial regimens have been proposed for the empirical therapy of NHAP; however, there are still very few data from controlled clinical trials that assess outcome. The clinical trials that have been completed support the concept that an early switch from intravenous to oral therapy can be successfully used to treat pneumonia affecting frail, often seriously ill, groups of patients. Annual influenza vaccine should be offered to all nursing home residents. This practice is about 50% effective in preventing hospitalisation and pneumonia, and about 80% effective in preventing death. The same level of evidence is not available to support the use of pneumococcal vaccine in this group; however, current practice suggests that all nursing home residents receive this vaccine on admission and once every 6 years thereafter. Frequently, knowledge about pneumonia is not applied as optimally as should be done. Care maps have been shown to reduce length of stay and shorten the time from emergency room entry until administration of antibiotic therapy by up to 3 hours. Areas for urgent research attention in patients with NHAP are: (a) proper studies to define the microbiological aetiology of NHAP (this requires bronchoscopy with sampling of the distal airways using a protected bronchial brush); (b) randomised controlled clinical trials of sufficient size to determine whether one antibiotic regimen is superior to another (currently most trials are designed to show that the agent under study is equivalent to a currently used agent); and (c) end-of-life decision making in the nursing home population.

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OBJECTIVE: Oral contraceptive (OC) steroids alter the disposition of numerous drugs, including corticosteroids. We investigated the pharmacokinetics and pharmacodynamics of methylprednisolone. METHODS: Twelve women (six women used OC steroids and six women did not) received intravenous methylprednisolone (0.6 mg/kg ideal body weight). Methylprednisolone disposition was assessed from plasma concentrations. Pharmacodynamic parameters measured were plasma cortisol, whole blood histamine (reflecting basophils), and blood helper T lymphocytes. RESULTS: Methylprednisolone clearance was significantly decreased in the women who used OC steroids (0.298 versus 0.447 L/hr/kg), resulting in a longer elimination half-life (2.20 versus 1.72 hours). With use of indirect response models, significant differences were observed with the cortisol and basophil responses. A larger value for the concentration that inhibits the zero-order production rate by 50% (0.37 versus 0.11 ng/ml) was observed in the women who used OC steroids for suppression of cortisol secretion, indicating less sensitivity to the suppressive effects of methylprednisolone. Greater net suppression of basophils was observed in the users of OC steroids (area under the response curve, 694 versus 401 ng x hr/ml). No differences were observed for helper T-cell responses. CONCLUSION: OC steroids appear to inhibit methylprednisolone metabolism. However, mixed changes in several responses occur, indicating that women can probably receive similar doses of methylprednisolone irrespective of OC steroid use.

PIP: At the Buffalo General Hospital in New York, researchers randomly assigned 6 healthy, nonobese women, 30-36 years old and using a triphasic oral contraceptive (OC) (Triphasil 28, Wyeth-Ayerst Laboratories), to either the baseline phase group or the group receiving an intravenous bolus of methylprednisolone sodium succinate at a dose of 0.6 mg/kg ideal body weight during the 2-week period after ovulation (i.e., luteal phase). These women were compared with 6 other women who did not use OCs but did receive the same dose of methylprednisolone. The purpose was to determine whether the adrenosuppressive, anti-inflammatory, and immunosuppressive effects of methylprednisolone differ in OC users. OC users experienced slower clearance of methylprednisolone (33% slower) than controls. This slower clearance rate contributed to a longer elimination half-life for methylprednisolone (2.2 vs. 1.72 hours; p 0.05). OC users also had a rate of slower elimination of cortisol than controls (0.180 vs. 0.276 hr-1; p 0.05). They had higher mean cortisol levels than controls (136 vs. 65 ng/ml). Women who used OCs for suppression of cortisol secretion had a larger value for the concentration of cortisol that suppresses the zero-order production rate by 50% (0.37 vs. 0.11 ng/ml; p 0.05), suggesting a decreased sensitivity to the effects of methylprednisolone on cortisol suppression. OC users experienced a greater net suppression of basophils at drug effect than at baseline. Methylprednisolone appeared to have no effect on helper T-cell responses. These findings suggest that OCs inhibit methylprednisolone metabolism. Since there were inconsistent changes in several responses, women can likely receive similar doses of methylprednisolone irrespective of OC use.

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OBJECTIVE: To report a case of an HIV-positive man who received sequential didanosine and pentamidine treatment and subsequently developed acute clinical pancreatitis. CASE SUMMARY: In June 1992 didanosine 200 mg po bid was initiated in a 30-year-old man with AIDS. After a 22-week course of didanosine, the patient was hospitalized and didanosine was discontinued on day 4. The patient then received 8 days of treatment for a presumed Pneumocystis carinii pneumonia (PCP) with pentamidine 4 mg/kg/d iv. As the patient responded clinically to therapy, he was discharged home to complete a 21-day course of pentamidine. On day 14 of therapy, the patient experienced nausea, vomiting, diarrhea, fatigue, and was hypotensive. The dosage of pentamidine was reduced by 50 percent. After receiving 18 doses of pentamidine, treatment was discontinued, as symptoms had worsened and serum amylase and lipase concentrations were elevated. The patient was hospitalized and the diagnosis of acute clinical pancreatitis was made. After a 21-day hospitalization, the patient was discharged home in fair condition on hyperalimentation. DISCUSSION: Potential causes of pancreatitis, including opportunistic infections, neoplasms, and drugs, are discussed. The most probable factors associated with pancreatitis in our patient are didanosine and pentamidine therapy. CONCLUSIONS: As our patient developed pancreatitis following sequential administration of didanosine and pentamidine, it would be prudent to monitor for signs and symptoms of pancreatitis in similar cases. In addition, didanosine should be discontinued during and for one week following treatment of PCP when pentamidine is used.

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