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Data Analysis Tutorials. Review step-by-step guidance on using NHANES data. Low Resolution Video. Low Resolution Video. Last Reviewed: May 13, 2024. Source: National Center for Health Statistics.
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- Overview
- Evidence and Rationale
- Recommendations
- Discussion
- References
Antimicrobial stewardship. The 2019 report on antimicrobial resistance threats in the United States (3) highlights that antimicrobial stewardship, i.e., the development, promotion, and implementation of activities to ensure the appropriate use of antimicrobials, remains a major public health concern. Data continue to document the impact of antimicrobials on the microbiome and on pathogenic organisms. A recent investigation comparing children who received twice-yearly azithromycin with children who received placebo found that the gut’s resistome, a reservoir of antimicrobial resistance genes in the body, had increased determinants of macrolide and nonmacrolide resistance, including beta-lactam antibiotics, among children receiving azithromycin (10). A higher proportion of macrolide resistance in nasopharyngeal Streptococcus pneumoniae was demonstrated in communities receiving mass administration of oral azithromycin (11). Azithromycin resistance has been demonstrated in another STI, Mycoplasma genitalium, and sexually transmissible enteric pathogens (e.g., Shigella and Campylobacter) (12–14). In addition, evidence supports increasing concern for the efficacy of azithromycin to treat chlamydial infections, especially rectal infections (15,16).
GISP data show that the ceftriaxone MIC50 and MIC90 (MIC required to inhibit growth of 50% and 90% of organisms, respectively) were only one doubling dilution higher during 2014–2018, compared with the respective ceftriaxone MIC50 and MIC90 during 1992–1995 (1). Although dual drug therapy with different mechanisms of action (ceftriaxone and azithromycin) might have mitigated emergence of reduced susceptibility to ceftriaxone in N. gonorrhoeae, concerns regarding potential harm to the microbiome and the effect on other pathogens diminishes the benefits of maintaining dual therapy as the recommended treatment regimen.
Pharmacokinetic and pharmacodynamic considerations. Ceftriaxone is a bactericidal third-generation cephalosporin with widely variable pharmacokinetics (17). Efficacy is best predicted by time that the serum free (i.e., unbound) drug concentration remains higher than the organism’s MIC (fT>MIC). Although no human data exist confirming the length of time above the MIC required to eradicate gonorrhea at different anatomic sites, using Monte Carlo modeling, ceftriaxone has been estimated to require concentrations higher than the strain MIC for approximately 20–24 hours for effective urogenital gonorrhea treatment (18). A 250 mg ceftriaxone dose does not reliably achieve levels higher than an MIC ≥0.125 μg/mL for an extended duration (18). A murine model was used to estimate pharmacokinetic and pharmacodynamic parameters needed for cure at urogenital sites for both susceptible and resistant strains of N. gonorrhoeae (19). Investigators evaluated the efficacy of various ceftriaxone doses (0.06–30 mg/kg body weight). The lowest ceftriaxone dose that was 100% effective at eradicating the susceptible organism (MIC = 0.008 μg/mL) 48 hours after treatment was 5 mg/kg body weight, which corresponded to an fT>MIC of 23.6 hours, consistent with the Monte Carlo simulation (18,19). Translating into human doses, a 500-mg dose corresponds to 5 mg/kg body weight (80–100 kg) human, whereas 250 mg only corresponds to 3 mg/kg body weight for an 80 kg person.
The pharynx tends to be screened less often (1) than other anatomic sites, and globally, most reported ceftriaxone-based regimen treatment failures have involved treatment of pharyngeal gonorrhea (20). Ceftriaxone concentrations tend to be more variable in the pharynx, and treatment of N. gonorrhoeae likely requires longer times above the strain’s MIC (21,22). Continued uncertainty regarding ceftriaxone pharmacokinetics and pharmacodynamics in treating pharyngeal gonorrhea and the higher likelihood of treatment failures at this site strengthen the recommendation for an increase in the ceftriaxone dosage to 500 mg.
For treatment of uncomplicated urogenital, rectal, or pharyngeal gonorrhea, CDC recommends a single 500 mg IM dose of ceftriaxone (Box). For persons weighing ≥150 kg (300 lbs), a single 1 g IM dose of ceftriaxone should be administered. If chlamydial infection has not been excluded, doxycycline 100 mg orally twice a day for 7 days is recommended. When ceftriaxone cannot be used for treating urogenital or rectal gonorrhea because of cephalosporin allergy, a single 240 mg IM dose of gentamicin plus a single 2 g oral dose of azithromycin is an option. Gastrointestinal symptoms, primarily vomiting within 1 hour of dosing, have been reported among 3%–4% of treated persons (26). If administration of IM ceftriaxone is not available, a single 800 mg oral dose of cefixime is an alternative regimen. However, cefixime does not provide as high, or as sustained, bactericidal blood levels as does ceftriaxone and demonstrates limited treatment efficacy for pharyngeal gonorrhea (27,28).
In cases where gonococcal expedited partner therapy (provision of prescriptions or medications for the patient to take to a sex partner without the health care provider first examining the partner) is permissible by state law and the partner is unable or unlikely to seek timely treatment, the partner may be treated with a single 800 mg oral dose of cefixime, provided that concurrent chlamydial infection in the patient has been excluded. Otherwise, the partner may be treated with a single oral 800 mg cefixime dose plus oral doxycycline 100 mg twice daily for 7 days.
In cases of suspected cephalosporin treatment failure, clinicians should obtain relevant clinical specimens for culture and antimicrobial susceptibility testing, consult an infectious disease specialist or STD clinical expert (https://www.stdccn.org/external icon) for guidance in clinical management, and report the case to CDC through state and local public health authorities within 24 hours. Health departments should prioritize notification and culture evaluation for the patient’s sex partner(s) from the preceding 60 days for those with suspected cephalosporin treatment failure or persons whose gonococcal isolates demonstrate reduced susceptibility to cephalosporins.
A test-of-cure is unnecessary for persons with uncomplicated urogenital or rectal gonorrhea who are treated with any of the recommended or alternative regimens; however, for persons with pharyngeal gonorrhea, a test-of-cure is recommended, using culture or nucleic acid amplification tests 7–14 days after initial treatment, regardless of the treatment regimen. Because reinfection within 12 months ranges from 7% to 12% among persons previously treated for gonorrhea (29,30), persons who have been treated for gonorrhea should be retested 3 months after treatment regardless of whether they believe their sex partners were treated. If retesting at 3 months is not possible, clinicians should retest within 12 months after initial treatment.
Continued support of gonorrhea prevention and control efforts remains fundamental, and preventing antibiotic resistance is crucial. The pharmacokinetics and pharmacodynamics of ceftriaxone indicate that a 500 mg dose in an average-weight U.S. adult achieves sufficiently high serum levels for an adequate duration to eradicate infection, even with wide pharmacokinetic variability. The high frequency of pharyngeal gonorrhea with substantial underscreening and the increased understanding of wide individual pharmacokinetic and pharmacodynamic variability has contributed to the recommendation for the increased ceftriaxone dose. These recommendations also include a test-of-cure for persons with pharyngeal gonorrhea to ensure eradication or detection of a possible treatment failure.
Emerging antimicrobial resistance affects gonorrhea treatment recommendations and other STIs. CDC recommends ceftriaxone monotherapy for treatment because N. gonorrhoeae remains highly susceptible to ceftriaxone, azithromycin resistance is increasing, and prudent use of antimicrobial agents supports limiting their use. Continuing to monitor for emergence of ceftriaxone resistance through surveillance and health care providers’ reporting of treatment failures will be essential to ensuring continued efficacy of recommended regimens.
1.CDC. Sexually transmitted disease surveillance 2018. Atlanta, GA: US Department of Health and Human Services, CDC; 2019. https://www.cdc.gov/std/stats18/STDSurveillance2018-full-report.pdfpdf icon
2.Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999;75:3–17. CrossRefexternal icon PubMedexternal icon
3.CDC. Antibiotic resistance threats in the United States, 2019. Atlanta, GA: US Department of Health and Human Services, CDC; 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdfpdf icon
4.Workowski KA, Berman S; CDC. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010;59(No. RR-12). PubMedexternal icon
5.Workowski KA, Bolan GA; CDC. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015;64(No. RR-3). PubMedexternal icon
6.CDC. Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep 2007;56:332–6. PubMedexternal icon
Bacterial Vaginosis. Print. BV is a vaginal dysbiosis resulting from replacement of normal hydrogen peroxide and lactic-acid–producing Lactobacillus species in the vagina with high concentrations of anaerobic bacteria, including G. vaginalis, Prevotella species, Mobiluncus species, A. vaginae, and other BV-associated bacteria.
2024年5月8日 · Download CDC’s free Milestone Tracker App. View. Skills such as taking a first step, smiling for the first time, and waving “bye bye” are called developmental milestones. Children reach milestones in how they play, learn, speak, act, and move. Click on the age of your child to see the milestones: 2 months. 4 months.
2021年7月23日 · Summary These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11–14, 2019. The ...
National Institute for Occupational Safety and Health (NIOSH) The Occupational Safety and Health Act of 1970 established NIOSH as a research agency focused on the study of worker safety and health, and empowering employers and workers to create safe and healthy workplaces. Site Index.
