Drug Shortage: Erythromycin Ophthalmic Ointment
On July 7, 2022, the Food and Drug Administration (FDA) reported a shortage of erythromycin ophthalmic ointment, which is the only recommended regimen to prevent ophthalmia neonatorum caused by N. gonorrhoeae. If erythromycin ointment is unavailable, infants at risk for exposure to N. gonorrhoeae, especially those born to a mother at risk for gonococ15cal infection or with no prenatal care, can be administered ceftriaxone 25–50 mg/kg body weight IV or IM, not to exceed 250 mg in a single dose. Please see the CDC drug notice for additional guidance.
New HIV Testing Recommendations for PrEP Patients
Based on the 2021 CDC Pre-Exposure Prophylaxis (PrEP) for the Prevention of HIV Infection in the United States, A Clinical Practice Guideline, VDH now recommends adding the qualitative HIV-1 RNA test to the HIV Ag/Ab 4th generation test for those who:
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- Have taken oral PrEP or Post-Exposure Prophylaxis (PEP) medications in the past three months, or
- Have received a cabotegravir injection in the past twelve months
Clinical trials found that the medications used for PrEP can suppress early viral replication, which can affect the timing of antibody development – a delay by a mean of 62 days in the cabotegravir group and by 34 days in the oral PrEP group. The HIV-1 RNA test detects HIV genetic material, not antibodies, so the results are not affected by taking PrEP medications.
For questions, please reach out to Jenny Calhoun, HIV/STD/Viral Hepatitis Nurse Consultant, at jenny.calhoun@vdh.virginia.gov, or (804) 864-7328.
To view the full 2021 CDC PrEP Guidelines, visit https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf.
New Resources for Expedited Partner Therapy (EPT)
New resources have been added for Expedited Partner Therapy for health professionals. These resources include:
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- A general EPT in Virginia FAQ
- An EPT Fact Sheet for Medical Providers
- An EPT Fact Sheet for Pharmacists, and
- EPT Fact sheets for patients and partners when you provide them with medications or prescriptions as part of EPT
These resources can be found on the Health Professionals page: https://www.vdh.virginia.gov/disease-prevention/hcw/#STD_Resources.
Viral Hepatitis Recommendations
CDC Recommendations for Hepatitis C Screening Among Adults
CDC now recommends one-time hepatitis C testing of all adults (18 and older) and all pregnant women during every pregnancy. CDC continues to recommend people with risk factors, including people who inject drugs, be tested regularly.
For more information, visit the full recommendations at CDC Recommendations for Hepatitis C Screening Among Adults — United States, 2020 | MMWR.
Updated Hepatitis B Vaccination Recommendations
The Advisory Committee on Immunization Practices (ACIP) recommends hepatitis B vaccination among all adults aged 19-59 years and adults 60 years and older with risk factors for hepatitis B or without identified risk factors but seeking protection.
Learn more by visiting the full recommendations: https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7113a1-h.pdf.
New HIV PrEP Option Approved by FDA
The first long-acting injectable that prevents HIV has been approved by the U.S. Food and Drug Administration (FDA).
On December 20, 2021, the U.S. Food and Drug Administration (FDA), approved Apretude® (cabotegravir) for HIV pre-exposure prophylaxis, or PrEP. The medication is approved for adults and adolescents - 15 years old and older - weighing at least 77 pounds, and who are at risk of getting HIV through sexual activity. All other options have been oral tablets. In approving the new medication, the FDA noted that an injectable could make it easier for patients to maintain adherence, a key factor in the effectiveness of PrEP as an HIV prevention strategy.
Apretude is given first as two initiation injections administered one month apart, and then every two months thereafter. Potential patients may take an oral lead-in for four weeks to assess tolerance for the medication. Side effects include: injection site reaction, headache, pyrexia, fatigue, back pain, myalgia and rash. Manufacturer’s warnings also include precautions regarding hypersensitivity reactions, hepatotoxicity and depressive disorders.
For more information, visit the press release from the FDA.
STI Treatment Guidelines, 2021 Update
CDC has issued updated guidelines for the treatment of sexually transmitted infections (STI). Following adjustments to gonorrhea treatment practices (published in late- 2020), the new guidelines include other notable updates:
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- Updated treatment recommendations for chlamydia, trichomoniasis, and pelvic inflammatory disease
- Updated treatment recommendations for uncomplicated gonorrhea in neonates, children, and other specific clinical situations (e.g., proctitis, epididymitis, sexual assault) which builds on broader treatment changes published in Morbidity and Mortality Weekly Report.
- Information on FDA-cleared diagnostic tests for Mycoplasma genitalium and rectal and pharyngeal chlamydia and gonorrhea
- Expanded risk factors for syphilis testing among pregnant patients
- Recommended two-step serologic testing for diagnosing genital herpes simplex virus
- Harmonized recommendations for human papillomavirus vaccination with the Advisory Committee on Immunization Practices
- Recommended universal hepatitis C testing in alignment with CDC’s 2020 hepatitis C testing recommendations
Key resources are available on the CDC website.
**Please note: the summary above is not comprehensive; refer to the updated guidelines for the complete set of recommendations, including alternative treatment regimens and treatment regimens for special populations.
Archived Updates
CDC has revised its recommendation for the treatment of uncomplicated gonorrhea in adults. The new recommendations, briefly summarized below, are available in the 2020 Update to CDC's Treatment for Gonococcal Infections. This new recommendation supersedes the gonorrhea treatment recommendation included in the 2015 STD Treatment Recommendations. The summary below is not comprehensive and only includes the most important highlights; refer to the whole document for the complete set of recommendations.
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- Treat gonorrhea infections with a single 500 mg intramuscular injection of ceftriaxone. Dual therapy with azithromycin is no longer the recommended approach.
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- For persons weighing ≥150 kg (300 lb), 1 g of IM ceftriaxone should be administered.
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- A test-of-cure is not needed for people diagnosed with uncomplicated urogenital or rectal gonorrhea unless symptoms persist.
- A test-of-cure is recommended in people with pharyngeal gonorrhea 7-14 days after the initial treatment, regardless of the regimen.
- Patients who have been treated for gonorrhea should be retested three months after treatment to ensure there is no reinfection.
- Oral doxycycline (100 mg twice daily for 7 days) should now be administered when chlamydial infection has not been excluded, unless the patient is pregnant. During pregnancy, azithromycin 1 g as a single dose is recommended to treat chlamydia.
- When ceftriaxone cannot be used for treating urogenital or rectal gonorrhea because of cephalosporin allergy, a single 240 mg intramuscular injection of gentamicin plus a single 2 g oral dose of azithromycin is an option.
- As always, facilitate partner testing and treatment.
- Treat gonorrhea infections with a single 500 mg intramuscular injection of ceftriaxone. Dual therapy with azithromycin is no longer the recommended approach.
HHS released the first-ever STI national strategic plan to address the public health crisis caused by alarming increases in rates of sexually transmitted infections (STIs) in the U.S. The STI National Strategic Plan 2021-2025 (STI Plan) sets national goals, objectives, and strategies to respond to the STI epidemic. The STI Plan could not come at a better time: STI rates continue their historic climb contributing to a myriad of adverse health effects, including infant death and increased HIV infections. The STI Plan aims to provide a roadmap for a broad range of stakeholders—including public health, health care, government, community-based organizations, educational institutions, researchers, private industry, and academia—to develop, enhance and expand STI prevention and care programs at the local, state, tribal and national levels over the next five years.
On September 8, 2020, the Centers for Disease Control and Prevention (CDC) issued a Dear Colleague letter addressing the recent national shortage of chlamydia (CT) and gonorrhea (GC) diagnostic test kits. This letter includes guidance on the prioritization of testing certain populations when diagnostic test kits are limited. VDH has issued guidance, based on CDC’s Tier 2 guidance, that should be followed if a shortage of CT/GC diagnostic test kits is identified. When the availability of CT/GC diagnostic test kits returns to normal levels, screening according to the CDC’s Sexually Transmitted Diseases Treatment Guidelines, 2015 should be resumed.
On April 14, 2020, the Food and Drug Administration (FDA) reported a shortage of azithromycin tablets, which is the recommended treatment for chlamydia, nongonococcal urethritis, and cervicitis. Azithromycin is also part of the recommended dual therapy for gonorrhea. Alternative treatment regimens for chlamydia, nongonococcal urethritis, and cervicitis are outlined in the 2015 STD Treatment Guidelines. Temporary alternative regimens for gonorrhea, in addition to syndromes which empiric gonorrhea treatment is indicated, are addressed in the guidance on STD treatment during the COVID-19 pandemic. For more information regarding the availability of azithromycin, visit the FDA Drug Shortage Website.
DGI occurs when the sexually transmitted pathogen Neisseria gonorrhoeae invades the bloodstream and spreads to distant sites in the body. Infection leads to clinical manifestations like septic arthritis, polyarthralgia, tenosynovitis, petechial/pustular skin lesions, bacteremia, or, on rare occasions, endocarditis or meningitis. Cultures from disseminated sites of infection are often negative, and mucosal sites of infection (e.g. urogenital, rectal, or pharyngeal) are often asymptomatic and not tested before empiric antimicrobial treatment is started, despite having a higher diagnostic yield. As a result, DGI is usually a clinical diagnosis without microbiologic confirmation, which likely contributes to underdiagnosis and delays in treatment and reporting. If there is clinical suspicion for DGI, nucleic acid amplification test (NAAT) and culture specimens from urogenital and extragenital mucosal site(s), as applicable, should be collected and processed, in addition to culture specimens from disseminated sites of infection (e.g., skin, synovial fluid, blood, or cerebrospinal fluid [CSF]). All N. gonorrhoeae isolates in DGI cases should be tested for antimicrobial susceptibility, which requires culture. Management of DGI cases should be guided by the CDC STD Treatment Guidelines. Hospitalization and consultation with an infectious disease specialist are recommended for initial therapy.
What You Can Do
To better understand the magnitude of DGI in Virginia and the US, providers should take the following actions:
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- Continue to report confirmed DGI cases to CDC as gonorrhea via routine case notification mechanisms; if there are positive laboratory results from multiple anatomic sites, prioritize the sterile site (i.e., blood, CSF, or other aspirate) as the reported specimen source when reporting the case. Regardless of clinical manifestations, isolation of gonorrhoeaefrom a sterile site (e.g., blood, synovial fluid, or CSF) would constitute confirmed DGI.
- gonorrhoeaeisolates from sterile sites should be reported to VDH within 24 hours. Report electronically here.
- Any laboratory confirmed or clinically suspected cases of DGI, including those empirically treated without laboratory evidence of gonorrhoeae, should be reported to VDH within 24 hours. Report electronically here.
- Obtain NAAT and culture specimens of genital and extragenital sites (if exposed) before initiating empiric antimicrobial treatment for patients with clinical findings suggestive of DGI.
- Facilitate submission of any culture isolates from sterile and/or genital and extragenital sites to CDC. Instructions on isolates submission can be found here.
- Continue to report confirmed DGI cases to CDC as gonorrhea via routine case notification mechanisms; if there are positive laboratory results from multiple anatomic sites, prioritize the sterile site (i.e., blood, CSF, or other aspirate) as the reported specimen source when reporting the case. Regardless of clinical manifestations, isolation of gonorrhoeaefrom a sterile site (e.g., blood, synovial fluid, or CSF) would constitute confirmed DGI.
All N. gonorrhoeae isolates from sterile sites should be submitted to CDC for comprehensive antimicrobial susceptibility testing (AST) using agar dilution and whole genome sequencing (WGS). Resources
On March 5, 2019, the Food and Drug Administration (FDA) released a report on a shortage of erythromycin (0.5%) ophthalmic ointment. This is a serious problem for a number of reasons. Erythromycin (0.5%) ophthalmic ointment is the only antibiotic ointment currently recommended and the only drug cleared by the FDA for the prophylaxis of gonococcal ophthalmia neonatorum. Furthermore, gonorrhea ocular prophylaxis of newborns is mandated by law in most states and is considered standard neonatal care. This prophylaxis was recently reaffirmed by the USPSTF. If erythromycin ointment is not available, CDC recommends that neonates at risk for exposure to N. gonorrhoeae during delivery (especially those born to a mother at risk for gonococcal infection or with no prenatal care) be administered ceftriaxone 25–50 mg/kg IV or IM, not to exceed 125 mg in a single dose. For more information, please see the 2015 STD Treatment Guidelines and if questions, please contact Roxanne Barrow, MD, MPH, Medical Epidemiologist, (rbarrow@cdc.gov; 404-639-8503). Other topical medications are not recommended:
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- Tetracycline ophthalmic ointment and silver nitrate are no longer available in the United States;
- Gentamicin was associated with chemical conjunctivitis during the last erythromycin shortage;
- Povidone-iodine has limited data on its benefits and harms.
It is important to remember that prenatal screening is the best method for preventing gonococcal ophthalmia neonatorum among newborns! All pregnant women < 25 years of age and women > 25 at increased risk should be screened for N. gonorrhoeae at the first prenatal care visit and again at the third trimester if risk continues during pregnancy. Also, all females treated for gonorrhea should be retested 3 months following treatment. Please notify health care providers, hospitals and pharmacists of the shortage of erythromycin (0.5%) ophthalmic ointment so they are aware and remind them of gonorrhea screening recommendations for pregnant females. As we have recommended with previous shortages, please ask providers, hospitals and pharmacists to report to you any challenges in procuring product and alert CDC of any problems. Current information regarding the availability of erythromycin (0.5%) ophthalmic ointment is available at the FDA Drug Shortage Website.
Diluents for Ceftriaxone are in limited supply. Ceftriaxone is the last remaining known effective antimicrobial for the treatment of uncomplicated gonorrhea and dual therapy with azithromycin has been recommended to mitigate the emergence of Ceftriaxone resistance in the United States. The usual preparation for ceftriaxone is a powder form reconstituted with an appropriate diluent. One percent lidocaine without epinephrine is the preferred diluent to use by most STD clinical experts in an effort to minimize significant patient discomfort from the intramuscular injection. The full product insert for ceftriaxone lists other diluents for consideration. The FDA continues to work closely with manufacturers and to update their website related to the availability of all of the diluents. Diluents currently in shortage: 1% lidocaine without epinephrine, sterile water, and 0.9% sodium chloride CDC is interested in hearing about any shortages of 1% lidocaine without epinephrine or if any provider can’t procure diluents at all and is not treating gonorrhea patients with ceftriaxone as a result.
There is good news related to the supply of Penicillin G benzathine (Bicillin L-A®) and Penicillin G procaine in the United States. As mentioned in earlier letters, Pfizer is the sole manufacturer of Penicillin G benzathine (Bicillin L-A®) and Penicillin G procaine in the United States. After a protracted shortage, Penicillin G benzathine (Bicillin L-A®) is back to normal supply levels and has been moved by the FDA to a resolved shortage status. As supply can be fragile when there is only one manufacturer and Penicillin G benzathine is the only recommended treatment for syphilis in adults in the 2015 CDC STD Treatment Guidelines we encourage the following:
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- Ask health care providers and pharmacists to continue to report to you any challenges in procuring Penicillin G benzathine product and report these challenges to CDC. We need to keep ahead of supply problems given the unprecedented current levels of syphilis in the United States.
Note: Doxycycline is an alternative treatment for non-pregnant patients and only if a medical contraindication exists such as an IgE mediated allergy to penicillin. Efficacy of doxycycline has not been well-studied, is considered inferior to penicillin and if utilized close follow-up of the patient is indicated.
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- If a patient is unable to afford Penicillin G benzathine (Bicillin L-A®) out of pocket or because of co-pays, please contact the local or State STD Director in your jurisdiction for assistance.
- Encourage clinicians with questions about STD clinical management to contact the on-line National Network of STD Clinical Prevention Training Centers (NNPTC) STD Clinical Consultation Network (https://www.stdccn.org).
After an even more protracted shortage, Penicillin G procaine is now available at normal supply levels and the FDA has recently moved it to the resolved shortage status. Penicillin G procaine is an alternative regimen for outpatient treatment of neurosyphilis and congenital syphilis. As with Penicillin G benzathine, we encourage the following:
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- Notify health care providers and pharmacists of the availability of Penicillin G procaine so they are aware that product is available.
- Ask them to report to you any challenges in procuring product and report these challenges to CDC.
Last Updated: December 20, 2022