Christopher M. Bland

A Review of Antibiotic Use in Pregnancy

During pregnancy, untreated sexually transmitted or urinary tract infections are associated with significant morbidity, including low birth weight, preterm birth, and spontaneous abortion. Approximately one in four women will be prescribed an antibiotic during pregnancy, accounting for nearly 80% of prescription medications in pregnant women. Antibiotic exposures during pregnancy have been associated with both short‐term (e.g., congenital abnormalities) and long‐term effects (e.g., changes in gut microbiome, asthma, atopic dermatitis) in the newborn. However, it is estimated that only 10% of medications have sufficient data related to safe and effective use in pregnancy. Antibiotics such as beta‐lactams, vancomycin, nitrofurantoin, metronidazole, clindamycin, and fosfomycin are generally considered safe and effective in pregnancy. Fluoroquinolones and tetracyclines are generally avoided in pregnancy. Physiologic changes in pregnancy lead to an increase in glomerular filtration rate, increase in total body volume, and enhanced cardiac output. These changes may lead to pharmacokinetic alterations in antibiotics that require dose adjustment or careful monitoring and assessment.

Vancomycin MIC susceptibility testing of methicillin-susceptible and methicillin-resistant Staphylococcus aureus isolates: a comparison between Etest® and an automated testing method.

Background: Vancomycin treatment failures and increased mortality have been reported in methicillin-resistant Staphylococcus aureus (MRSA) isolates with minimum inhibitory concentrations (MICs) >1 &mgr;g/mL. Most of this data utilized manual testing to determine the MIC. Recent vancomycin treatment guidelines do not specify the optimal testing method to define the MIC. Methods: Over a twelve-month study period, we compared manual susceptibility testing by Etest® (AB Biodisk, Solna, Sweden) with automated testing by MicroScan Walk-Away® (Dade Behring, Inc., East Mississauga, Ontario) to determine the difference in the MICs among 383 sequential clinical S aureus isolates. Results: Manual testing demonstrated MICs of 1.5 &mgr;g/mL or 2.0 &mgr;g/mL in 90% and 86% of MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) isolates, respectively. Automated testing revealed MICs of 2.0 &mgr;g/mL for 56% and 54% of MRSA and MSSA isolates, respectively. The manual MIC test by Etest® was >1 &mgr;g/mL in 87% of MRSA isolates and 86% of methicillin-susceptible S aureus isolates in which the automated MIC result was 1 &mgr;g/mL. This same finding occurred in 94% (17/18) of S aureus isolates causing non-skin/skin structure infections. Among all subgroups of isolates, manual testing demonstrated statistically significant higher MICs compared to automated testing. Conclusions: MIC results generated by the Etest® consistently revealed a one dilution higher vancomycin MIC compared to MicroScan®. Automated MIC results of invasive MRSA isolates should be confirmed by manual Etest® to ensure identification of those isolates with vancomycin MICs >1&mgr;g/mL that are at risk for vancomycin treatment failure or increased mortality.

Safety and Effectiveness of Daptomycin Across a Hospitalized Obese Population: Results of a Multicenter Investigation in the Southeastern United States

Data are limited for antimicrobial outcomes in obese patients. This study investigated the safety and clinical outcomes of daptomycin therapy in a hospitalized obese population in the southeastern United States.

Perioperative management of bariatric surgery patients

PURPOSE The perioperative management of bariatric surgery patients is described. SUMMARY Obesity and anatomical changes create unique challenges for clinicians when caring for bariatric surgery patients. Common bariatric surgery procedures performed include Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric banding. Pain management in the acute postoperative period depends on careful dosing of opioid agents and the use of adjunctive agents. Prevention and management of infectious complications include appropriate surgical prophylaxis, monitoring and rapid treatment of suspected intra-abdominal infections, and detection and treatment of Helicobacter pylori infection. Venous thromboembolism (VTE) prophylaxis and treatment are complicated by obesity, and the use of pharmacologic agents must be balanced with bleeding risk. Bleeding is a serious complication that should be closely monitored in the immediate postoperative period. Blood products remain first-line therapy for the treatment of bleeding in this population. Acute differences in drug absorption as well as emerging hormonal changes necessitate the immediate postoperative adjustment of chronic medications to ensure both safety and efficacy. Pharmacists are valuable members of interprofessional teams for bariatric surgery patients because they provide expertise on the availability of dosage forms and dosage modification to ensure that patient pharmacotherapy is not interrupted; assist in the management of hypertension, diabetes, and psychotropic medications; and ensure appropriate antimicrobial prophylaxis and VTE prophylaxis and treatment dosages. CONCLUSION The management of patients in the perioperative period of bariatric surgery requires appropriate selection and dosing of medications for pain management and treatment of infectious complications, VTE, bleeding, and other chronic diseases.

Penicillin skin testing as an antimicrobial stewardship initiative

PURPOSE An initiative to determine the effects of penicillin skin testing (PST) from an antimicrobial stewardship perspective is described. SUMMARY Penicillin allergy is one of the most frequently reported allergies; however, only about 10% of self-reports of penicillin allergy are accurate. Incorrect penicillin allergies are therefore a significant barrier to antimicrobial stewardship, with important clinical and economic implications, including increased antimicrobial resistance, an increased overall cost of care, increased length of stay, and, ultimately, increased mortality. As part of its antimicrobial stewardship program, a community health system launched a PST initiative in order to optimize therapy, reduce adverse events acquisition costs, and minimize development of antibiotic resistance. The PST program involves the use of a standardized protocol for the assessment of hypersensitivity to penicillin in patients with suspected penicillin allergy. Among 36 patients who completed the PST protocol during an eight-month period, all had a negative result; in 27 of those patients, a conversion of antimicrobial therapy to a penicillin or cephalosporin was implemented as a direct result of PST. CONCLUSION In patients with a self-reported penicillin allergy, PST led to a reduction in the use of carbapenems, aztreonam, vancomycin, and other broad-spectrum agents within a health system. A decrease in drug costs was documented in a sample of patients switched to a penicillin or a cephalosporin after PST.

Identification of optimal renal dosage adjustments for high-dose extended-infusion cefepime dosing regimens in hospitalized patients

OBJECTIVES The objective of this study was to identify optimal renal dose adjustments for 2 g of cefepime every 8 h as a 3 h infusion where the probability of target attainment was optimized and drug accumulation was minimal. METHODS Embedded with a population pharmacokinetic model derived in a population of hospitalized patients with varying degrees of renal function, a series of 5000-subject Monte Carlo simulations using ADAPT 5 were performed for 3 h infusions of 2 g every 6, 8, 12 and 24 h. To assess exposure profiles across various levels of renal function, the estimated CLCR was fixed at values between 20 and 150 mL/min. For each regimen examined, the fraction of simulated subjects who achieved free drug concentrations in excess of the MIC for ≥60% of the dosing interval (60% fT > MIC) at the various CLCR levels was determined and this information was used to identify optimal renal dose adjustments without profound drug exposure. RESULTS In the Monte Carlo simulations, modification of the parent regimen (2 g every 8 h) to 2 g every 6 h for CLCR >120 mL/min and extension of the dosing interval to every 12 and 24 h at CLCR of 60 and 20 mL/min, respectively, provided favourable probability of target attainment profiles without profound drug exposure. CONCLUSIONS The findings from this study identified renal dose alteration regimens that yielded favourable pharmacodynamic profiles without excessive drug exposure. As these findings were based on mathematical models, they should be validated in the clinical arena.

Musculoskeletal Safety Outcomes of Patients Receiving Daptomycin with HMG-CoA Reductase Inhibitors

ABSTRACT Daptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. Detailed information, including treatment indication and duration, infecting pathogen, baseline and subsequent CPK levels, and presence of myalgias or muscle complaints, was collected. Myalgias were noted in 3/49 (6.1%) patients receiving combination therapy compared with 5/171 (2.9%) of patients receiving daptomycin alone (P = 0.38). CPK elevations of >1,000 U/liter occurred in 5/49 (10.2%) patients receiving combination therapy compared to 9/171 (5.3%) patients receiving daptomycin alone (P = 0.32). Two of five patients experiencing CPK elevations of >1,000 U/liter in the combination group had symptoms of myopathy. Three patients (6.1%) discontinued therapy due to CPK elevations with concurrent myalgias in the combination group versus 6 patients (3.5%) in the daptomycin-alone group (P = 0.42). CPK levels and myalgias reversed upon discontinuation of daptomycin therapy. Overall musculoskeletal toxicity was numerically higher in the combination group but this result was not statistically significant. Further prospective study is warranted in a larger population.

Randomized trial of OFIRMEV versus placebo for pain management after laparoscopic sleeve gastrectomy

BACKGROUND OFIRMEV is an intravenous form of acetaminophen approved by the Food and Drug Administration for use as an antipyretic and treatment of mild to moderate pain alone or in conjunction with opioid medications. Intravenous APAP use in postsurgical pain management has been reported to decrease opioid usage, time to rescue dose, and subjective pain. OBJECTIVES We used a placebo-controlled, randomized double-blind study to test the efficacy of OFIRMEV in decreasing opioid use and subjective pain after laparoscopic sleeve gastrectomy. SETTING U.S. military training hospital. METHODS Thirty-four patients who met criteria were enrolled and randomly assigned to 2 separate limbs of the study. The OFIRMEV and placebo groups had similar mean age ranges (48±11 and 50±11 yr) and a female/male ratio of 5:1 and 6:1, respectively. The patients received an intraoperative dose and then postoperative administration of intravenous OFIRMEV 1 g or placebo every 6 hours for 24 hours in addition to fentanyl via patient-controlled analgesia. Subjective pain scores, the total amount of fentanyl used, time to rescue of first narcotic dose, and total postanesthesia care unit (PACU) narcotic use were measured during the first 24 hours after surgery. RESULTS Subjective pain score was significantly decreased compared with baseline at 12, 16, and 20 hours after surgery in OFIRMEV-treated patients but not in the placebo group. However, total narcotic use, time to rescue of first narcotic dose, and total PACU narcotic dose were not statistically different between the 2 groups. CONCLUSION Intravenous OFIRMEV use caused a modest but statistically significant decrease in subjective pain without affecting narcotic use after laparoscopic sleeve gastrectomy. (Surg Obes Relat Dis 2015;0:000-00.)

Hypertension and diabetes mellitus medication management in sleeve gastrectomy patients.

Obesity is a worldwide epidemic with far-reaching complications, including hypertension, diabetes mellitus, obstructive sleep apnea, and many others. It is estimated that over 1.5 billion people worldwide are obese or overweight.[1][1] Lifestyle modifications and medication therapy alone or in

Neisseria gonorrhoeae and fosfomycin: Past, present and future

Drug-resistant Neisseria gonorrhoeae has become a global health concern that requires immediate attention. Due to increasing resistance to cephalosporins, pursuing novel alternatives for treating N. gonorrhoeae infections is paramount. Whilst new drug development is often cumbersome, reviving antiquated antibiotic agents for treatment of modern infections has become prevalent in clinical practice. Fosfomycin exhibits bactericidal activity through a unique mechanism of action, and a variety of organisms including N. gonorrhoeae are susceptible. In vitro studies have demonstrated that fosfomycin can retain activity against ceftriaxone-resistant N. gonorrhoeae; however, it remains unclear whether there is synergy between fosfomycin and other antibiotics. Clinical investigations evaluating fosfomycin for the treatment of N. gonorrhoeae infections are confounded by methodological limitations, none the less they do provide some perspective on its potential role in therapy. Future studies are needed to establish a safe, convenient and effective fosfomycin regimen for treating N. gonorrhoeae infections.