The preparation of compounded sterile products in pharmacy has evolved into a complex, highly regulated, and technical practice.

This was prompted in large part by many highly publicized negative safety events that revealed shortcomings in the process. One of the most infamous cases is the 2012 fungal meningitis outbreak that originated at the New England Compounding Center, which resulted in 753 documented patient exposures and 64 deaths.

The enactment of section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) in 1997 has had the most significant impact on sterile drug compounding practice. It essentially created a provision that separated traditional pharmacy compounding from pharmaceutical manufacturing. In 2008, United States Pharmacopeia (USP) chapter <797> established standards related to sterile compounding in 503A facilities. And in 2013, the Drug Quality and Security Act amended the FD&C Act by adding section 503B. This allowed a new type of compounder, the outsourcing facility, to bridge the gap between pharmaceutical companies and pharmacies. The production of compounded sterile drug products for human use is divided into 2 categories: 503A and 503B.

Facilities that compound under section 503A perform patient-specific compounding, such as compounding that takes place in home infusion or hospital pharmacies or physician offices. This type of compounding is widely referred to as "traditional compounding." 503A facilities are exempt from just 3 sections of the FD&C Act: those concerning current good manufacturing practice (cGMP), some labeling requirements, and FDA approval prior to marketing. They remain subject to compliance with all other pieces of the act. The FDA typically only conducts for-cause inspections of 503A facilities that result from complaints. Routine regulation of these compounders is primarily a state function, and most state boards of pharmacy require that pharmacies meet or exceed USP guidelines. Additionally, most health care accreditation organizations reference USP <797> in their standards related to sterile drug compounding.

Organizations that compound under section 503B are primarily considered outsourcing facilities. That is, they produce large batches of drug products, with or without a prescription, that are sold to health care facilities for administration to patients. To register as an outsourcing facility, the organization must compound sterile human drug products, though it can compound nonsterile products, as well. Outsourcing facilities are not required to be licensed pharmacies but are required to have a licensed pharmacist either perform or directly oversee all compounding activities.

 Products compounded under 503B are subject to cGMP, which outlines much more strict conditions for the preparation and distribution of compounded drugs than what is required of 503A facilities. One of the advantages of following cGMP is that 503B pharmacies can offer products with extended beyond0use dates.

To ensure continuing compliance with cGMP standards, the FDA does for-cause and routine inspections of all 503B facilities, acting as the primary regulatory body for these organizations. As of January 29, 2021, there were 68 facilities across the United States registered with the FDA as outsourcing facilities for the compounding of sterile human drugs. Of the 503B facilities that have been open long enough to have been inspected by the FDA, 93% have been issued a Form 483 (a citation), which speaks to the seriousness with which the agency takes drug compounding.

 The FDA makes all issued Form 483 citations public, and they are accessible on its website.

Although the compounding of sterile human drug products is a requirement to register as an outsourcing facility, the FDA has issued guidance related to other practices for 503B facilities. This includes biological products, compounded drugs for animals, conventional manufacturing of FDA-approved drug products, and repackaging of medications. All of these resources can be found on the FDA's website. 

Although the increased scrutiny of sterile drug compounding has resulted in stricter regulation of the practice, it also has resulted in more opportunity for pharmacists. As the recognized experts in the field, pharmacists should lead the charge to innovate in both 503A and 503B settings, which will continue to change and grow. The division of sterile pharmacy compounding into 503A and 503B practices also provides health care organizations with a wide range of options. The focus on patient safety and cost-efficient care within health care has never been more intense. Organizations should assess their needs and determine under what circumstances each type of compounding can and should be used to maximize the care that they are able to offer.

1. Multistate outbreak of fungal meningitis and other infections. Centers for Disease Control and Prevention. October 30, 2015. Accessed February 15, 2021. https://www.cdc.gov/hai/outbreaks/meningitis.html

2. FD&C Act provisions that apply to human drug compounding. FDA. Updated July 14, 2020. Accessed February 15, 2021. https://www.fda.gov/drugs/human-drug-compounding/fdc-act-provisions-apply-human-drug-compounding

3. Registered outsourcing facilities. FDA. Updated February 26, 2021. Accessed March 3, 2021. https://www.fda.gov/drugs/human-drug-compounding/registered-outsourcing-facilities

Articles

Pharmacists can lead to the charge to innovate in both 503A and 503B settings, which are poised to change and grow.

More Scrutiny Means Strict Regulation and Opportunity

Antimicrobial stewardship program (ASP) development in the United States has expanded significantly over the past 2 decades, with 85% of acute-care hospitals demonstrating program that contain all of the CDC's core elements of antimicrobial stewardship.

Yet, despite an ever-expanding understanding of inpatient antimicrobial stewardship practices, approximately 80% to 90% of human antibiotic consumption takes place in the outpatient setting.

 The new ambulatory standard from the Joint Commission for the Accreditation of Healthcare Organizations (TJC) took effect January 1, 2020. Since then, ASPs have focused on the use of antimicrobials in the outpatient setting.

 The addition of an outpatient ASP to a facility's armamentarium is both difficult and valuable, given several features of the setting that complicate efforts, including a lack of feasibility of tradition primary stewardship tactics, large volume of outpatient providers, and a vast array of services.

The quest for outpatient antimicrobial stewardship in the ambulatory setting may start with understanding 2 key documents: the CDC's "Core Elements of Outpatient Antimicrobial Stewardship" and the TJC's "Antimicrobial Stewardship in Ambulatory Health Care" standard.

 Both focus on 4 core elements of stewardship: leadership commitment; action in policy and practice; education; and data analysis and reporting.

 The success of any ASP can be sourced back to the commitment level of an institution's leadership, the prescribers within the institution, and the ASP team. Without institutional leadership commitment to the practice, effort and enthusiasm are unlikely to gain traction. Leadership commitment may be demonstrated in several ways. One of the most critical is through the designation of health-system and/or local leaders for ambulatory ASP.

 This should, ideally, be accompanied by dedicated practice time and the incorporation of clear expectations and specific responsibilities into job descriptions. Consider writing and publicly displaying a commitment to antimicrobial stewardship practices to demonstrate institutional commitment to patients receiving care.

 The first step toward designing and implementing interventions as an outpatient ASP is to define an annual target. Outpatient antimicrobial use takes place across an array of locations and specialties, including emergency departments, medical offices, retail clinics, and urgent-care facilities. It is important that programs focus on specific goals to allow for appropriate tracking of association metrics. Urgent-care visits have some of the highest rates of antimicrobial prescribing per patient encounter and should not be overlooked when designing ASP plans.

 One recent review of antimicrobial prescribing across a network of urgent-care clinics found that respiratory encounters accounted for 41.8% of all visits.

 Furthermore, 21.3% of visits for respiratory infections unlikely to benefit from antimicrobial therapy still resulted in an antibiotic prescription. When considering encounter-level outpatient ASP targets, genitourinary infections, respiratory, and skin and soft tissue likely represent the 3 most logical focus areas, with respiratory infections the most commonly studied target in the literature.

The next step is to implement best practices that favorably affect antimicrobial prescribing pertaining to the established goal. One opportunity is to formalize delayed prescribing and watchful waiting processes, which have resulted in 60% or greater reductions in antibiotic use compared with patients given an immediate prescription.

 Another option is to implement evidence-based practice guidelines or protocols for appropriate prescribing of antimicrobials.

 Enhancing clinical decision support within the electronic medical record and requiring indication for antimicrobial prescriptions can also facilitate appropriate prescribing. However, there are barriers, including limitations in information (IT) support and resistance to change in prescriber workflow.

Educational efforts that target both clinicians and patients are essential.

 It is critical that prescribers be made aware of the annual goal and provided tools to support it. Emerging literature has identified that many factors, beyond gaps in knowledge, contribute to inappropriate prescribing by clinicians.

 These can be emotional, financial, or social, including the belief that some patients may be impossible to satisfy without giving them an antibiotic prescription, the perceived correlation between antibiotic prescribing and value, and the potential for negative implications brought about by failure to prescribe antibiotics.

 Provider education should include a review of clinical content as well as communication tools and support to overcome psychosocial pressures for unnecessary antibiotic prescribing.

Significant gaps in patient knowledge about appropriate antimicrobial use also represent a substantial opportunity.

 Give patients a clear rationale when antibiotics are not indicated, including the potential unintended consequences of antimicrobial use, such as adverse events, increased cost, infection-related complications, and resistance development.

 In addition to the prescriber-patient interaction, use educational materials, such as posters, pamphlets, and videos, to ensure that patients receive a consistent message. To address the perception of value when antibiotics are not indicated, provide patients with written instructions for symptomatic treatment and a contingency plan for follow-up if symptoms worsen.

Tracking antimicrobial prescribing practices and providing regular feedback to clinicians are essential for both progress toward established goals and sustained culture change.

 Unfortunately, this element may be met with a host of barriers, such as a lack of IT support and limits surrounding data extraction. Moreover, it has been shown that a large portion of antimicrobial prescribing occurs because of nonvisit care, resulting in outpatient ASP efforts failing to target approximately half of antibiotic prescribing.

Apply selected metrics to the established goals, including analysis of encounter types, percentage of visits resulting in an antimicrobial prescription, and prescribing rate by antimicrobial class.

 In addition to primary metrics, formalize a plan for counterbalance measures to track unforeseen complications that may arise from decreased antimicrobial use.

 Although the capability to thoroughly evaluate outpatient data is requisite, it is also imperative that these data are communicated regularly to providers. Prescriber-level interventions, such as dashboards and individualized letters, can promote individual behavioral change through peer comparison.

Although the CDC core elements provide a road map for successful implementation of an outpatient ASP, there may be detours. ASPs in the early phases of outpatient implementation should perform a comparison of current performance with desired performance, through which gaps in practice can be identified. Begin improvements with high-impact, low-effort interventions. For items that require more effort, develop an action plan with a realistic timeline. Although the road to successful deployment may seem similar to the pursuit of the Holy Grail, the growth and progress that a program encounters along the way will make the journey worthwhile.

1. CDC. Core elements of hospital antibiotic stewardship programs. Updated November 16, 2020. Accessed February 8, 2021. https://www.cdc.gov/antibiotic-use/core-elements/hospital.html

2. Sanchez GV, Fleming-Dutra KE, Roberts RM, Hicks LA. Core elements of outpatient antibiotic stewardship. 

. 2016;65(6):1-12. doi:10.15585/mmwr.rr6506a1

3. The Joint Commission. R3 report issue 23: antimicrobial stewardship in ambulatory health care. Accessed February 8, 2021. https://www.jointcommission.org/standards/r3-report/r3-report-issue-23-antimicrobial-stewardship-in-ambulatory-health-care/

4. Quality Improvement Organizations. A field guide to antibiotic stewardship in outpatient settings. July 2018. Accessed February 8, 2021. https://qioprogram.org/sites/default/files/editors/141/C310_Field_Guide_20180730_FNL.pdf

5. Palms DL, Hicks LA, Bartoces M, et al. Comparison of antibiotic prescribing in retail clinics, urgent care centers, emergency departments, and traditional ambulatory care settings in the United States. 

. 2018;178(9):1267-1269. doi:10.1001/jamainternmed.2018.1632

6. Stenehjem E, Wallin A, Fleming-Dutra KE, et al. Antibiotic prescribing variability in a large urgent care network: a new target for outpatient stewardship. 

. 2020;70(8):1781-1787. doi:10.1093/cid/ciz910

7. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. 

. 2016;315(17):1864-1873. doi:10.1001/jama.2016.4151

8. White AT, Clark CM, Sellick JA, Mergenhagen KA. Antibiotic stewardship targets in the outpatient setting. 

 2019;47(8):858-863. doi:10.1016/j.ajic.2019.01.027

9. Kohut MR, Keller SC, Linder JA, et al. The inconvincable patient: how clinicians perceive demand for antibiotics in the outpatient setting. 

 2020;37(2):276-282. doi:10.1093/fampra/cmz066

10. Wattengel BA, DiTursi S, Schroeck JL, Sellick JA, Mergenhagen KA. Outpatient antimicrobial stewardship: targets for urinary tract infections. 

. 2020;48(9):1009-1012. doi:10.1016/j/ajic.2019.12.018

11. CDC. The core elements of outpatient antibiotic stewardship appendix. Accessed February 8, 2021. https://www.cdc.gov/antibiotic-use/community/pdfs/16_268900-A_CoreElementsOutpatient_appendix_508.pdf

12. Little P, Moore M, Kelly J, et al. Delayed antibiotic prescribing strategies for respiratory tract infections in primary care: pragmatic, factorial randomized controlled trial. 

13. McCormick DP, Chonmaitree T, Pittman C, et al. Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment. 

. 2005;115(6):1455-1465. doi:10.1542/peds.2004-1665

14. Seipel MBA, Prohaska ES, Ruisinger JF, Melton BL. Patient knowledge and experiences with antibiotic use and delayed antibiotic prescribing in the outpatient setting. 

. Published online: December 13, 2019. doi:10.1177/0897190019889427

15. Fischer MA, Mahesri M, Lii J, Linder JA. Non-infection-related and non-visit-based antibiotics prescribing is common among Medicaid patients. 

 2020;39(2):280-288. doi:10.1377/hlthaff.2019.00545

16. Hallsworth M, Chadborn T, Sallis A, et al. Provision of social normal feedback to high prescribers of antibiotics in general practice: a pragmatic national randomized controlled trial. 

. 2016;387(10029):1743-1752. doi:10.1016/S0140-6736(16)00215-4

The Society of Infectious Diseases Pharmacists (SIDP) is an association of pharmacists and other allied healthcare professionals who are committed to promoting the appropriate use of antimicrobial agents and supporting practice, teaching, and research in infectious diseases. We aim to advance infectious diseases pharmacy and lead antimicrobial stewardship in order to optimize the care of patients. To learn more about SIDP, visit

Infectious Diseases Focus

Developing an antimicrobial stewardship program is arduous but valuable; commitment from leadership is the first step.

Outpatient ASPs Are Worth the Journey

Pneumonia is the leading infectious cause of mortality in the United States, with timely antibiotic therapy serving as the foundation of treatment.

Appropriate risk assessment of patients presenting with community-acquired pneumonia (CAP) is imperative to guide empiric therapy. Given increasing resistance in the community, the term 

 This term was accompanied by increased use of broad-spectrum agents. When the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) updated guidelines for treating adults with CAP in 2019, HCAP was eliminated in favor of assessment of local and patient-specific risk factors for 

A recent retrospective cohort study of 88,605 patients with CAP hospitalized within the Veterans Health Administration system sought to examine the addition of empiric anti-MRSA therapy to standard therapy.

 This study included patients typically thought to benefit from anti-MRSA therapy, including individuals admitted to intensive care units, patients with a history of MRSA colonization or infection, or those with a MRSA-positive nasal polymerase chain reaction swab or MRSA found in blood or respiratory cultures within 2 days of admission. Using a weighted propensity score analysis, receipt of anti-MRSA therapy plus standard therapy was associated with a significantly increased adjusted risk of death, acute kidney injury (AKI), and infections due to vancomycin-resistant 

Investigators concluded that the study questions the assumption that the "benefit of more potent antibiotics during the empirical phase exceeds the harms."

Empiric anti-MRSA therapy continues to represent an area of opportunity for antimicrobial stewardship in the treatment of CAP.

The 2019 guidelines also removed the recommendation to cover anaerobes when aspiration pneumonia is suspected in favor of covering only in the setting of empyema or lung abscess. Aspiration pneumonia is associated with higher mortality than non-aspiration-related CAP, with anaerobes historically thought of as the primary pathogens.

 However, recent data show that anaerobes have a much lower incidence than previously thought. Some studies even postulate harm from administering unnecessary anaerobic therapy.

 In a recent, secondary analysis of the international, multicenter, point-prevalence study of adults hospitalized with CAP, 193 patients with aspiration CAP (ACAP) were examined.

 Hospitalized patients with ACAP had similar anaerobic flora to patients without aspiration risk factors. Despite this, a large proportion of CAP patients received antianaerobic therapy, regardless of aspiration or risk factors (72.5% of patients with ACAP, 53.4% of CAP patients with risk factors for aspiration, and 49.8% of CAP patients without risk factors). The study investigators support the guidelines in suggesting limiting antianaerobic therapy to patients with empyema or lung abscess.

The coronavirus disease 2019 (COVID-19) pandemic has affected patient care and provided an additional barrier to antibiotic stewardship. Viral respiratory infections from severe acute respiratory syndrome coronavirus 2 often present with similar signs and symptoms of a bacterial pneumonia, raising the concern for a bacterial coinfection.

 However, the frequency of bacterial coinfections remains low in patients with COVID-19. Study results show that patients presenting from the community have a low prevalence of bacterial coinfections ranging up to 4%.

 There is a slightly higher prevalence of secondary bacterial infections in hospitalized patients ranging from 7% to 14.3%.

 This rate is lower compared with other prominent viral respiratory infections. By comparison, the prevalence of bacterial coinfections in patients with influenza has been reported to be as high as 30%.

Although the frequency of bacterial coinfections is low, there is an increased risk of morbidity and mortality when treatment is delayed, thus creating difficulty in appropriate management of CAP. When there is a strong suspicion of a bacterial coinfection, it is appropriate to start empiric CAP therapy.

 Empiric antibiotic spectrum should correlate with patient-specific risk factors for multidrug-resistant organisms, as stated in the ATS/IDSA CAP guidelines.

 For patients with COVID-19 bacterial coinfection, 5 to 7 days of antibiotic therapy with clinical improvement is the typical recommended duration.

 However, coverage for bacterial coinfection is unnecessary in most situations, resulting in antibiotic overuse.

Use of diagnostic stewardship tools provides opportunities to optimize patient care. In patients with COVID-19 with a mild severity of illness, a normal procalcitonin level (<0.5 μg/L) correlates with a low likelihood of a bacterial infection and may guide clinicians toward discontinuing antibiotics.

 However, patients critically ill with COVID-19 may have an elevated procalcitonin level (>0.5 μg/L). Procalcitonin levels can be elevated, because of noninfectious causes, including acute respiratory distress, AKI, cardiogenic shock, and end-stage renal disease.

 An additional stewardship tool is MRSA nasal swabs, which can be used for patients with risk factors to reduce unnecessary MRSA coverage. These tools allow for prompt antibiotic cessation or deescalation to reduce exposure to unnecessary antibiotic therapy and decrease potential patient harm.

, a podcast by the Society of Infectious Diseases Pharmacists, has more information on controversies in the treatment of CAP.

1. Kochanek KD, Murphy SL, Xu J, Arias E. Deaths: final data for 2017. National Vital Statistics Reports. CDC. June 24, 2019. Accessed January 11, 2021. https://www.cdc.gov/nchs/data/nvsr/nvsr68/nvsr68_09_508.pdf

2. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. 

. 2005;171(4):388-416. doi:10.1164/rccm.200405-644ST

3. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. 

. 2007;44(suppl 2):27-72. doi:10.1086/511159

4. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia: an official clinical practice guidelines of the American Thoracic Society and the Infectious Diseases Society of America. 

. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST

5. Berger A, Edelsberg J, Oster G, Huang X, Weber DJ. Patterns of initial antibiotic therapy for community-acquired pneumonia in US hospitals, 2000 to 2009. 

. 2014;347(5):347-356. doi:10.1097/MAJ.0b013e318294833f

6. Jones BE, Ying J, Stevens V, et al. Empirical anti-MRSA vs standard antibiotic therapy and risk of 30-day mortality in patients hospitalized for pneumonia. 

. 2020;180(4):552-560. doi: 10.1001/jamainternmed.2019.7495

7. Lanspa MJ, Jones BE, Brown SM, Dean NC. Mortality, morbidity, and disease severity of patients with aspiration pneumonia. 

8. Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. 

 1999;115(1):178-183. doi:10.1378/chest.115.1.178

9. El-Solh AA, Pietrantoni C, Bhat A, et al. Microbiology of severe aspiration pneumonia in institutionalized elderly. 

. 2003;167(12):1650-1654. doi: 10.1164/rccm.200212-1543OC

10. Marin-Corral J, Pascual-Guardia S, Amati F, et al. Aspiration risk factors, microbiology, and empiric antibiotics for patients hospitalized with community-acquired pneumonia. 

. 2021:159(1):58-72. doi:10.1016/j.chest.2020.06.079

11. Langford BJ, So M, Raybardhan S, et al. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. 

. 2020;26(12):1622-1629. doi:10.1016/j.cmi.2020.07.016

12. Garcia-Vidal C, Sanjuan G, Moreno-Garcia E, et al; COVID-19 Researchers Group. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. 

. 2021;27(1):83-88. doi:10.1016/j.cmi.2020.07.041

13. Buehrle DJ, Decker BK, Wagener MM, et al. Antibiotic consumption and stewardship at a hospital outside of an early coronavirus disease 2019 epicenter. 

. 2020;64(11):e01011-e01020. doi:10.1128/aac.01011-20

14. Rawson TM, Moore LSP, Zhu N, et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing. 

. 2020;71(9):2459-2468. doi:10.1093/cid/ciaa530

15. Estenssoro E, Rios FG, Apezteguia C, et al. Pandemic 2009 influenza A in Argentina: a study of 337 patients on mechanical ventilation. 

. 2010;182(1):41-48. doi:10.1164/201001-0037OC

16. Martin-Loeches I, Sanchez-Corral A, Diaz E, et al; H1N1 SEMICYUC Working Group. Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus. 

. 2011;139(3):555-562. doi:10.1378/chest.10-1396

17. Rice TW, Rubinson L, Uyeki TM, et al. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. 

. 2012;40(5):1487-1498. doi:10.1097/ccm.0b013e3182416f23

18. Wu CP, Adhi F, Highland K. Recognition and management of respiratory co-infection and secondary bacterial pneumonia in patients with COVID-19. 

. 2020;87(11):659-663. doi:10.3949/ccjm.87a.ccc015

19. Spellberg B. The new antibiotic mantra-"shorter is better." 

. 2016;176(9):1254-1255. doi:10.1001/jamainternmed.2016.3646

20. Parente DM, Cunha CB, Mylonakis E, Timbrook TT. The clinical utility of methicillin-resistant staphylococcus aureus (MRSA) nasal screening to rule out MRSA pneumonia: a diagnostic meta-analysis with antimicrobial stewardship implications. 

21. Society of Infectious Disease Pharmacists. 

. Accessed February 22, 2021. https://sidp.org/Podcasts

Empiric anti-MRSA therapy is an area of opportunity for antimicrobial stewardship in the treatment of CAP.

Improve Care for Patients With Community-Acquired Pneumonia

The National Institutes of Health (NIH) estimates that ovarian cancer (OC) will have accounted for 1.2% of new cases and 2.3% of all cancer deaths in the United States in 2020.

The most recent global statistics from 2018 show that OC is ranked eighth in cancer incidence rates for women, with more than 295,000 or 3.8% cases diagnosed in 2018.

There are no routine screenings for OC, which often results in delayed diagnosis beyond stage I and II, secondary to generalized vague symptoms.

 About 70% of the cases are diagnosed as advanced stage III or IV OC.

 The patients' 5-year survival rate varies greatly, depending on the stage at which they are initially diagnosed (FIGURE

). The CDC reported that new cases are 10.2 of 100,000, with 6.6 of 100,000 women succumbing to death annually.

Patients in developed countries have a higher rate of OC, with a peak incidence occurring between 55 and 64 years of age with a higher prevalence in Caucasian women.

 The most common type of OC is epithelial, which accounts for about 90% of all cases, and the remaining 10% are considered to be nonepithelial.

 About 20% of all OCs have been associated with an inherited gene mutation, eg, BRCA1, BRCA2, MLH1, MSH2. This malignancy has been linked to 1 of 3 hereditary patterns: ovarian cancer alone, ovarian cancer plus breast cancer, and ovarian cancer plus colon cancer.

 Women of Ashkenazi Jewish and Eastern European descent are more likely to be carriers of 

 gene mutations and therefore are at an increased risk of developing OC.

The National Comprehensive Cancer Network (NCCN) does not offer screening recommendations for ovarian cancer. Online table 1

 outlines common symptoms that might be produced by OC. If a patient is experiencing any of these signs or symptoms for greater than 2 weeks, diagnostic tests such as a CA-125 blood test, transvaginal ultrasound, or vaginal pelvic exam may be ordered to investigate the presence of OC.

 The staging of OC is determined postsurgically, which should be performed by a gynecologic oncologist and then examined microscopically by a pathologist.

Treatment options for OC include chemotherapy, hormone therapy, immunotherapy, radiation, surgery, and targeted therapy (Table 2

 The NCCN Clinical Practice Guidelines for OC recommend that the primary treatment consist of debulking surgery, plus systemic chemotherapy in most patients.

Clinicians use genetic testing to assess for specific gene mutations, such as 

, homologous-recombination deficiency, which will guide treatment decisions.

 This allows clinicians to prescribe a targeted therapy that includes poly-ADP ribose polymerase (PARP) inhibitors and/or vascular endothelial growth factor inhibitors.

Systemic immunotherapy enhances the activity of the immune system. Immune checkpoint inhibitors target key surface markers, eg, cytotoxic T-lymphocyte-associated protein 4, programmed cell death ligand, and programmed cell death protein 1.

Hormone therapy involves the use of hormones or hormone-blocking agents acting as anti-estrogen agents to suppress OC tumor growth. This type of therapy involves 3 classes of drugs: aromatase inhibitors, luteinizing-hormone-releasing hormone agonists, and tamoxifen. This mode of systemic therapy is rarely employed in epithelial OC but is more commonly used in refractory ovarian stromal tumors.

PARP inhibitors are vital in the treatment and maintenance of OC and may improve outcomes. Some recent clinical trials, ie, PAOLA-1/ENGOT-OV26, PRIMA/ENGOT-OV26, and SOLO-1, (Online table 3

Clinical trials evaluating combination products, eg, cediranib and olaparib, in patients that are considered to platinum-resistant and -sensitive, are showing promise. Cediranib, a VEGF inhibitor with olaparib, a PARP inhibitor, restricts blood supply to the area promoting apoptosis of the cancerous cells. Preliminary reports from the ICON 9 study demonstrate a significant improvement in progression-free survival.

OC negatively affects the lives of many women. It continues to remain one of the most lethal malignancies, despite continuing efforts and constant advances in treatments. The poor clinical outcomes associated with OC are attributable to chemotherapy resistance, its increased heterogeneity, and the ineffective tools for detecting the disease early in its course. New treatments are needed to enhance cure rates and provide long-term disease stability against platinum-resistance OC. Cellular and immune therapies combined with genetic testing and precision assays (biomarkers) are promising strategies that will inevitably lead to more favorable clinical outcomes. Accelerated research and novel approaches will also invariably spawn better therapeutic options to extend the life expectancy and improve the health of patients with OC.

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3. Stages of ovarian cancer. Ovarian Cancer Research Alliance. Accessed February 14, 2021. https://ocrahope.org/patients/about-ovarian-cancer/staging/

4. Gaona-Luviano P, Medina-Gaona LA, Magana-Perez K. Epidemiology of ovarian cancer. 

5. Ovarian germ cell tumors treatment (PDQ)-health professional version. National Cancer Institute. Updated September 3, 2020. Accessed February 14, 2021. https://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq

6. Risk factors. Ovarian Cancer Research Alliance. Accessed February 14, 2021. https://ocrahope.org/patients/about-ovarian-cancer/risk-factors/

7. Ovarian germ cell tumors treatment (PDQ)-patient version. National Cancer Institute. Updated January 8, 2021. Accessed February 14, 2021. https://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq

8. About ovarian cancer. Ovarian Cancer Research Alliance. Accessed February 14, 2021. https://ocrahope.org/patients/about-ovarian-cancer/

9. Treatment. Ovarian Cancer Research Alliance. Accessed February 14, 2021. https://ocrahope.org/patients/about-ovarian-cancer/treatment/

10. Kaplan DA. Overview of the updated NCCN guidelines on ovarian cancer. Journal of Clinical Pathways. June 17, 2020. Accessed February 14, 2021. https://www.journalofclinicalpathways.com/overview-updated-nccn-guidelines-ovarian-cancer

11. Borella F, Ghisoni E, Giannone G, et al. Immune checkpoint inhibitors in epithelial ovarian cancer: an overview on efficacy and future perspectives. 

. 2020;10(3):146. doi:10.3390/diagnostics10030146

12. Gershenson DM, Bodurka DC, Coleman RL, Lu KH, Malpica A, Sun CC. Hormonal maintenance therapy for women with low-grade serous cancer of the ovary or peritoneum. 

. 2017;35(10):1103-1111. doi:10.1200/JCO.2016.71.0632

13. Shylasree TS, Richa B, Lavanya G, Gulia S. Molecular signatures of gynecological cancers: clinicians perspective. 

14. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. 

 2018;379(26):2495-2505. doi:10.1056/NEJMoa1810858

15. Gonazlez-Martin A, Pothuri B, Vergote I, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. 

. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

16. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. 

. 2019;381(25):2416-2428. doi:10.1056/NEJMoa1911361

17. Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. 

. 2019;381(25):2403-2415. doi:10.1056/NEJMoa1909707

18. Clovis Oncology announces completion of target enrollment in the ATHENA trial, a phase 3 maintenance treatment study in front-line, newly-diagnosed advanced ovarian cancer. News release. Clovis Oncology. June 10, 2020. Accessed February 10, 2021. https://ir.clovisoncology.com/investors-and-news/news-releases/press-release-details/2020/Clovis-Oncology-Announces-Completion-of-Target-Enrollment-in-the-ATHENA-Trial-a-Phase-3-Maintenance-Treatment-Study-in-Front-line-Newly-Diagnosed-Advanced-Ovarian-Cancer/default.aspx

19. Mirza MR, Coleman RL, Gonzalez-Martin A, et al. The forefront of ovarian cancer therapy: update on PARP inhibitors. 

. 2020;31(9):1148-1159. doi:10.1016/j.annonc.2020.06.004

20. Liu JF, Barry WT, Birrer M, et al. Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer. 

. 2019;30(4):551-557. doi:10.1093/annonc/mdz018

21. Chandra A, Pius C, Nabeel M, et al. Ovarian cancer: current status and strategies for improving therapeutic outcomes. 

. 2019;8(16):7018-7031. doi:10.1002/cam4.2560

Oncology Focus

Guidelines typically recommend debulking surgery, plus systemic chemotherapy for most patients.

Explore Ovarian Cancer Treatments Through Clinical Trials

There have been significant modifications in breast cancer treatment due to the coroanvirus disease 2019 (COVID-19) pandemic, such as increased rates of neoadjuvant endocrine (NET) chemotherapy, genomic assay testing on core biopsies, and delays in planned surgeries, according to the results of a study presented at the 2020 San Antonio Breast Cancer Symposium, which was held virtually in December.

These modifications are consistent with the prioritization and treatment recommendations made by the COVID-19 Pandemic Breast Cancer Consortium.

During the study, investigators observed that a majority of patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive disease received guideline concordant neoadjuvant chemotherapy (NCT).

To get a clearer understanding of the rapid-care changes caused by the pandemic, the American Society of Breast Surgeons (ASBrS) developed a COVID-19 registry within the established Health Insurance Portability and Accountability Act-compliant Mastery of Breast Surgery Program to provide a snapshot of what has occurred in the field. Additionally, ASBrS developed the registry to support ongoing data entry and analysis and allow understanding of the impact of the pandemic on long-term breast cancer outcomes.

During the pandemic, many hospitals stopped some or all cancer surgeries to save personal protective equipment and minimize exposure. This, in turn, forced oncologic providers to quickly adjust patient treatment approaches.

For these reasons, investigators intended to describe the level of changes in patients with breast cancer that occurred in the initial months of the COVID-19 pandemic in the United States.

Modifications include high rates of neoadjuvant endocrine chemotherapy, genomic assay testing on core biopsies, and delays in planned surgeries. 

Health-System Edition March 2021

More Scrutiny Means Strict Regulation and Opportunity

Outpatient ASPs Are Worth the Journey

Improve Care for Patients With Community-Acquired Pneumonia

Explore Ovarian Cancer Treatments Through Clinical Trials

COVID-19 Pandemic Forces Changes in Breast Cancer Treatment

Change Management Is a Consideration Beyond the Pandemic

CIDP Has a Complex Pathophysiology and Path to Diagnosis

COVID-19 Vaccinations: It Takes a Village

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Digital Technology Has Changed the Landscape