Alternative drugs for the treatment of gonococcal infections: old and new.

INTRODUCTION: The rise in antibiotic resistance to N. gonorrhoeae poses a substantial threat to effective gonorrhea treatment. Historical progression of resistance from sulfonamides to the more recent declines in efficacy of fluoroquinolones and susceptibilities of ceftriaxone highlight the urgent need for novel therapeutic approaches, necessitating the examination of alternative and new antibiotics. AREAS COVERED: This review examines the potential of repurposing older antibiotics for gonorrhea treatment with a focus on their efficacy and limitations. These include aztreonam, ertapenem, and fosfomycin. New oral drugs zoliflodacin and gepotidacin are in late clinical development, but there are concerns regarding their effectiveness for extragenital infections and the development of resistance. EXPERT OPINION: While ceftriaxone remains the best treatment for gonorrhea across all anatomic sites, resistance may eventually limit its use. Among older antibiotics, ertapenem shows the most potential as an alternative but shares the same administrative drawbacks as ceftriaxone. New oral drugs zoliflodacin and gepotidacin initially appeared promising, but their efficacy for pharyngeal infections and potential for resistance development are concerning. Phase 3 trial results have not been made available except through press releases, which perpetuates concerns. Understanding pharmacokinetic and pharmacodynamic profiles of antibiotics will be key in optimizing future treatment recommendations.

The impact of pregnancy-related hormonal and physiological changes on antiseizure medications: expert perspective.

INTRODUCTION: Epilepsy is a disorder of recurrent, unprovoked seizures affecting approximately 15 million individuals of childbearing potential worldwide. Patients with epilepsy rely on regular daily therapy with antiseizure medications (ASMs). Furthermore, ASMs are also prescribed for other neuropsychiatric indications (e.g. bipolar disorder, pain, migraines) with over 2% of the pregnancies in the United States involving prenatal exposure to ASMs. AREAS COVERED: ASM concentrations are affected by hormonal and physiological changes in pregnancy, including increases in renal and hepatic blood flow, decreased protein binding, and changes in enzyme activity. Clearance changes typically reverse within a few weeks after delivery. During pregnancy, many ASMs, such as lamotrigine, levetiracetam, and oxcarbazepine, should have serum concentrations monitored and doses increased to maintain the individualized target range for seizure control. ASMs metabolized via glucuronidation, primarily lamotrigine, undergo marked increases in clearance throughout pregnancy, requiring about 3-fold the pre-pregnancy daily dose by delivery. Postpartum, ASM doses are usually decreased over several weeks to prevent drug toxicity. EXPERT OPINION: In the future, the development of a physiologically-based pharmacokinetic model for various ASMs may enable empiric dose adjustments in pregnancy without the difficulties of frequent therapeutic drug monitoring.

Can we use azithromycin eye drops for gonococcal ophthalmia prophylaxis in the United States?

INTRODUCTION: Neonatal ocular prophylaxis with 0.5% erythromycin ophthalmic ointment is mandated by law in many U.S. states despite its lack of efficacy in preventing chlamydial ophthalmia and the low incidence of gonococcal ophthalmia today. The current shortage of 0.5% erythromycin ophthalmic ointment is bringing into question what alternatives exist for neonatal ocular prophylaxis for the prevention of gonococcal ophthalmia. Providers in states with mandates are concerned with the implications of administering intramuscular ceftriaxone to every newborn. Azithromycin eye drops are being considered as an alternative. AREAS COVERED: This article discusses 1% azithromycin eye drops as an alternative to 0.5% erythromycin ophthalmic ointment. Clinical experience, side effects, resistance, logistics, pharmacokinetics, and pharmacodynamics are considered. EXPERT OPINION: Azithromycin eye drops are not an appropriate alternative to 0.5% erythromycin ophthalmic ointment for ocular prophylaxis. Prenatal screening and treatment of pregnant women is the most effective way to prevent neonatal ophthalmia. Mandates for universal prophylaxis should be withdrawn to avoid unnecessary medication administration, healthcare costs, and potential harm.

Neonatal ocular prophylaxis in the United States: is it still necessary?

INTRODUCTION: Much has changed since Credé reported that silver nitrate decreases the incidence of ophthalmia neonatorum. Prenatal screening and treatment of pregnant women for Neisseria gonorrhoeae became standard in the 1950s and for Chlamydia trachomatis in 1993. Neonatal gonococcal and chlamydial conjunctivitis are consequently uncommon today. Currently, only 0.5% erythromycin ophthalmic ointment is available in the United States (U.S.) for neonatal ocular prophylaxis, which is ineffective against C. trachomatis. AREAS COVERED: This article addresses the altered epidemiology of ophthalmia neonatorum in the U.S. since prophylactic practices began, the lack of data supporting ophthalmic erythromycin for prevention of neonatal gonococcal and chlamydial conjunctivitis, and the impact of prenatal screening and treatment of pregnant women for N. gonorrhoeae and C. trachomatis on conjunctivitis incidence. The authors discuss why erythromycin ophthalmic ointment is likely ineffective against gonococcal ophthalmia, including the development of macrolide resistance. Physiologic limitations and pharmacokinetic properties are considered with respect to ophthalmic erythromycin for the prevention of gonococcal and chlamydial conjunctivitis. EXPERT OPINION: Administration of erythromycin ophthalmic ointment for the prevention of neonatal conjunctivitis is not literature-supported. Prenatal screening and treatment of pregnant women is the most effective way to prevent ophthalmia neonatorum. National mandates for prophylaxis should be withdrawn.

Treatment options for neonatal infections in the post-cefotaxime era.

INTRODUCTION: Cefotaxime has been used for the management of neonatal infections since the 1990s for suspected meningitis and to mitigate gentamicin-associated renal injury. Its shortage in 2015 and subsequent removal from the U.S. pharmaceutical market forced providers to consider alternatives. Ceftriaxone, a cephalosporin with an identical antibacterial spectrum of activity to cefotaxime, is contraindicated in neonates due to its risk of biliary pseudolithiasis. Ceftazidime was recommended as an alternative by the American Academy of Pediatrics but is inequivalent. AREAS COVERED: This article addresses indications for cephalosporin use and considerations when selecting an alternative to cefotaxime. Differences among cefotaxime, ceftriaxone, ceftazidime, and cefepime are discussed and compared to the standard-of-care presumptive regimen, ampicillin, and gentamicin. The authors consider the data behind the neonatal contraindication to ceftriaxone and provide recommendations for their application to practice. EXPERT OPINION: The data against ceftriaxone use in neonates remain poor, particularly in the context of the cefotaxime shortage and lack of an equivalent alternative. Ceftriaxone could be considered in low-risk neonates without hyperbilirubinemia or exposure to calcium-containing fluids on a case-by-case basis. Ceftazidime monotherapy for presumptive management of neonatal infections is inappropriate; cefepime should be more frequently utilized in neonates who are poor candidates for ceftriaxone.

Incidence of Complications Associated with Parenteral Nutrition in Preterm Infants < 32 Weeks with a Mixed Oil Lipid Emulsion vs a Soybean Oil Lipid Emulsion in a Level IV Neonatal Intensive Care Unit.

BACKGROUND: Parenteral nutrition (PN) is crucial for the improvement of long-term outcomes in very low birth weight (VLBW) neonates. Lipid injectable emulsions are a key component of PN, as they contain essential fatty acids and provide energy critical for brain growth. Prolonged administration increases risk of intestinal failure-associated liver disease, including cholestasis, and other complications. METHODS: This is a retrospective, quasi-experimental cohort study of 215 VLBW neonates. The primary outcome was a change in direct bilirubin concentration. Secondary outcomes included change in total bilirubin concentration and incidences of cholestasis and other disease states associated with PN and prematurity. Cholestasis was defined as direct bilirubin ≥ 1.0 mg/dL with total bilirubin < 5.0 mg/dL or direct bilirubin > 20% of total bilirubin with total bilirubin > 5.0 mg/dL. RESULTS: Change in direct bilirubin concentration was not different between groups. Incidence of cholestasis was not different between groups per charted diagnosis or per study definition. Non-stage-0 retinopathy of prematurity, bronchopulmonary dysplasia, sepsis, and necrotizing enterocolitis were all lower in the mixed oil lipid emulsion group, which remained significant after adjustment for differences in gestational age, birth weight, and PN duration. CONCLUSIONS: Although mixed oil lipid emulsion was not found to be associated with a lower risk of cholestasis, it may decrease risks of other disease states associated with PN therapy.