Last data update: Nov 11, 2024. (Total: 48109 publications since 2009)
Records 1-29 (of 29 Records) |
Query Trace: Papp JR[original query] |
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CDC laboratory recommendations for syphilis testing, United States, 2024
Papp JR , Park IU , Fakile Y , Pereira L , Pillay A , Bolan GA . MMWR Recomm Rep 2024 73 (1) 1-32 This report provides new CDC recommendations for tests that can support a diagnosis of syphilis, including serologic testing and methods for the identification of the causative agent Treponema pallidum. These comprehensive recommendations are the first published by CDC on laboratory testing for syphilis, which has traditionally been based on serologic algorithms to detect a humoral immune response to T. pallidum. These tests can be divided into nontreponemal and treponemal tests depending on whether they detect antibodies that are broadly reactive to lipoidal antigens shared by both host and T. pallidum or antibodies specific to T. pallidum, respectively. Both types of tests must be used in conjunction to help distinguish between an untreated infection or a past infection that has been successfully treated. Newer serologic tests allow for laboratory automation but must be used in an algorithm, which also can involve older manual serologic tests. Direct detection of T. pallidum continues to evolve from microscopic examination of material from lesions for visualization of T. pallidum to molecular detection of the organism. Limited point-of-care tests for syphilis are available in the United States; increased availability of point-of-care tests that are sensitive and specific could facilitate expansion of screening programs and reduce the time from test result to treatment. These recommendations are intended for use by clinical laboratory directors, laboratory staff, clinicians, and disease control personnel who must choose among the multiple available testing methods, establish standard operating procedures for collecting and processing specimens, interpret test results for laboratory reporting, and counsel and treat patients. Future revisions to these recommendations will be based on new research or technologic advancements for syphilis clinical laboratory science. |
Complete Genome Sequence of Neisseria gonorrhoeae Multilocus Sequence Type ST7363 Isolated from Thailand.
Cherdtrakulkiat T , Wongsurawat T , Jenjaroenpun P , Sutheeworapong S , Leelawiwat W , Woodring JV , Dunne EF , Papp JR , Srifuengfung S , Tribuddharat C . Microbiol Resour Announc 2021 10 (41) e0057321 A Neisseria gonorrhoeae multilocus sequence type (MLST) ST7363 strain was isolated from a patient at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, in 2010 and completely sequenced. This strain is susceptible to ceftriaxone and cefixime. A complete circular chromosome and circular plasmids were assembled from combined Oxford Nanopore Technologies (ONT) and Illumina sequencing. |
Incidence and prevalence of Trichomonas vaginalis infection among persons aged 15-59: United States, 2018
Lewis FMT , Spicknall IH , Flagg EW , Papp JR , Kreisel KM . Sex Transm Dis 2021 48 (4) 232-237 BACKGROUND: Trichomonas vaginalis (TV) is a sexually transmitted parasite associated with multiple adverse outcomes in women. Estimating TV incidence is challenging due to its largely asymptomatic presentation. METHODS: Per capita prevalence was estimated using the National Health and Nutrition Examination Survey, 2013-2018. Incidence was estimated using ordinary differential equations assuming static incidence at steady state and fit using Bayesian techniques. Model inputs included estimates of: proportion of asymptomatic cases, natural clearance, and time to symptomatic treatment seeking. Posterior distributions were drawn, and uncertainty reported, from 25th (Q1) to 75th (Q3) percentiles. Aggregated measures were estimated by combining component distributions. RESULTS: Among 15-59 year-olds in 2018, the number of prevalent TV infections was 2.5 (Q1=2.4, Q3=2.7) million overall, 435,000 (Q1=382,000, Q3=492,000) among men, and 2.1 (Q1=2.0, Q3=2.2) million among women; the number of incident infections was 7.4 (Q1=6.6, Q3=8.3) million, 4.1 (Q1=3.5, Q3=4.9) million, and 3.2 (Q1=2.7, Q3=3.7) million among all persons, men, and women, respectively. Persons aged 15-24 years comprised 15.7% and 17.6% of all prevalent and incident infections, respectively; prevalence and incidence in both sexes increased with age. Incidence in both sexes were highly dependent upon estimates of natural clearance, which were based on little data. CONCLUSIONS: Prevalence and incidence of TV are substantial in the United States, particularly among those aged ≥25 years. Though estimated prevalence is higher in women, estimated incidence is higher in men. Data on key parameters of TV infection are limited; future research should focus on clarifying the natural history of TV. |
Pre-exposure prophylaxis use and detected sexually transmitted infections among men who have sex with men in the United States - National HIV Behavioral Surveillance, 5 US Cities, 2017
Chapin-Bardales J , Johnson Jones ML , Kirkcaldy RD , Bernstein KT , Paz-Bailey G , Phillips C , Papp JR , Raymond HF , Opoku J , Braunstein SL , Spencer EC , Khuwaja S , Wejnert C . J Acquir Immune Defic Syndr 2020 85 (4) 430-435 BACKGROUND: Men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) may be at high risk for bacterial sexually transmitted infections (STIs). We examined the prevalence of extragenital gonorrhea and chlamydia by PrEP status among a multisite sample of US MSM. METHODS: MSM aged ≥18 years were recruited through venue-based sampling to participate in the 2017 National HIV Behavioral Surveillance. In 5 cities (San Francisco, Washington DC, New York City, Miami, and Houston), participants completed a questionnaire, HIV testing, and pharyngeal and rectal STI specimen self-collection. We measured prevalence of pharyngeal and rectal gonorrhea and chlamydia among self-reported non-HIV-positive MSM who reported using or not using PrEP in the previous 12 months. RESULTS: Overall, 29.6% (481/1627) of non-HIV-positive MSM reported PrEP use in the past year. MSM who reported PrEP use were more likely to have any STI (ie, extragenital gonorrhea and/or chlamydia) than MSM not on PrEP [14.6% vs. 12.0%, adjusted prevalence ratio (aPR) = 1.5, 95% confidence interval (CI) : 1.1 to 2.0], reflecting differences in rectal chlamydia prevalence (8.7% vs. 6.0%, aPR = 1.6, 95% CI: 1.1 to 2.4). PrEP use was not associated with pharyngeal chlamydia, pharyngeal gonorrhea, or rectal gonorrhea. CONCLUSIONS: The prevalence of extragenital STI was high for both MSM on PrEP and those not on PrEP in the past year. MSM on PrEP were more likely to have rectal chlamydia but not pharyngeal STIs or rectal gonorrhea. Our findings support regular STI testing at exposed anatomic sites as recommended for sexually active MSM, including those on PrEP. |
Expanding US Laboratory Capacity for Neisseria gonorrhoeae Antimicrobial Susceptibility Testing and Whole Genome Sequencing through CDC's Antibiotic Resistance Laboratory Network.
Kersh EN , Pham CD , Papp JR , Myers R , Steece R , Kubin G , Gautom R , Nash EE , Sharpe S , Gernert KM , Schmerer M , Raphael BH , Henning T , Gaynor AM , Soge O , Schlanger K , Kirkcaldy RD , St Cyr SB , Torrone EA , Bernstein K , Weinstock H . J Clin Microbiol 2020 58 (4) US gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for Ng identification, capacity for culturing Ng in the US has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet, AST is critical for detecting and monitoring AR-Ng. In 2016, CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up national capacity for detecting several resistance threats including Ng. AR-Ng testing, a sub-activity of CDC's AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in MD, TN, TX, WA), and CDC's national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 Ng isolates, and CDC received 531 and 646 concerning isolates, and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported laboratory capacity for Ng-AST and associated genetic marker detection, expanding pre-existing notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention. |
Azithromycin susceptibility among Neisseria gonorrhoeae isolates and seasonal macrolide use
Olesen SW , Torrone EA , Papp JR , Kirkcaldy RD , Lipsitch M , Grad YH . J Infect Dis 2019 219 (4) 619-623 Rising azithromycin nonsusceptibility among Neisseria gonorrhoeae isolates threatens current treatment recommendations, but the cause of this rise is not well understood. We performed an ecological study of seasonal patterns in macrolide use and azithromycin resistance in N. gonorrhoeae, finding that population-wide macrolide use is associated with increased azithromycin nonsusceptibility. These results, indicative of bystander selection, have implications for antibiotic prescribing guidelines. |
Improving STD service delivery: Would American patients and providers use self-tests for gonorrhea and chlamydia
Pearson WS , Kreisel K , Peterman TA , Zlotorzynska M , Dittus PJ , Habel MA , Papp JR . Prev Med 2018 115 26-30 Chlamydia trachomatis (CT) and Neisseria gonorrhea (GC) are the most frequently reported notifiable diseases in the United States and costs for diagnosis and treatment of these two infections are approximately $700 million per year. A proposed new method for screening for these two infections is self-tests; similar to at-home pregnancy and HIV tests which do not include sending collected specimens to a laboratory for diagnosis. However, no such self-tests for sexually transmitted diseases (STD) have been approved by the Food and Drug Administration (FDA). To determine the acceptability of such a test, we used three surveys, conducted in 2017, including the American Men's Internet Survey, the SummerStyles survey, and the DocStyles survey to ask potential users about their interest in this type of test and how they might use it. Among our sampled population of men who have sex with men, 79.5% said they would prefer to take this type of test at home and 73.9% said they would be willing to pay at least $20 for the test. Among young adults (18-29years), 54.1% indicated that they would like to take this test at home and 64.5% were willing to pay more than $10 for such a test. Among sampled physicians, 85.1% were "likely" or "very likely" to use an FDA-approved STD self-test in their office to screen for CT or GC. Self-tests for STDs are on our horizon and we need to be prepared to integrate these tests into our healthcare systems. |
Performance of Chlamydia trachomatis OmcB ELISA in the serodiagnosis of Chlamydia trachomatis infection in women
Gupta K , Brown L , Bakshi RK , Press CG , Chi X , Gorwitz RJ , Papp JR , Geisler WM . J Clin Microbiol 2018 56 (9) Chlamydia trachomatis (CT) serological assays with improved sensitivity over commercially available assays are needed to evaluate the burden of CT infection and effectiveness of prevention efforts. We evaluated the performance of a CT outer membrane complex protein B (OmcB) ELISA in the detection of anti-CT antibody responses in CT-infected women. OmcB ELISA was less sensitive than our CT elementary body (EB ELISA), but was highly specific. The magnitude of the antibody response was higher in African Americans and those with prior CT infection. Unlike EB ELISA, the IgG1 response to CT OmcB was short-lived and not maintained by repeat CT infection. |
Preparing for the chlamydia and gonorrhea self-test
Peterman TA , Kreisel K , Habel MA , Pearson WS , Dittus PJ , Papp JR . Sex Transm Dis 2018 45 (3) e7-e9 New technology may soon allow individuals to test themselves for chlamydia and gonorrhea. These new self-tests might help increase screening, but they will also bring new issues for treatment, prevention, and surveillance. Providers will need to decide how to respond to patients who present after a positive screening test and how to approach partner testing and treatment. Research will be needed to identify approaches to increase screening using these tests. Laboratory-based surveillance will not capture infections if testing does not involve a laboratory, so new surveillance techniques will be needed. Self-tests are new tools that will soon be available. We should be prepared to use them. |
Susceptibility of Neisseria gonorrhoeae to gentamicin - Gonococcal Isolate Surveillance Project, 2015-2016
Mann LM , Kirkcaldy RD , Papp JR , Torrone EA . Sex Transm Dis 2018 45 (2) 96-98 The gentamicin minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae isolates were determined. Seventy-three percent of isolates demonstrated an MIC range of 8 to 16 mug/mL, and 27% demonstrated an MIC of 4 mug/mL or less. Significant associations between gentamicin MIC and resistance or reduced susceptibility to other antimicrobials were found. |
Accuracy and reproducibility of the Etest to detect drug-resistant Neisseria gonorrhoeae to contemporary treatment
Papp JR , Rowlinson MC , O'Connor NP , Wholehan J , Razeq JH , Glennen A , Ware D , Iwen PC , Lee LV , Hagan C . J Med Microbiol 2018 67 (1) 68-73 PURPOSE: Neisseria gonorrhoeae is a sexually transmitted bacterial pathogen that continues to evolve to become resistant to known antibiotics. In preparing for potential emergence, the Centers for Disease Control and Prevention recommends that clinical laboratories maintain or develop protocols to assess antibiotic susceptibly for this organism. This study examines the intra-laboratory variability of using the Etest method to provide consistent MIC values for N. gonorrhoeae and also compared the results of the Etest to known agar dilution MIC values. METHODOLOGY: Clinical N. gonorrhoeae isolates, 100 paired duplicates, were tested by eight laboratories for antibiotic susceptibility to ceftriaxone, cefixime and azithromycin using Etest strips.Results/Key findings. Overall, >80 % of the paired Etest MIC values were within one log2 dilution of the replicate. When compared to the agar dilution reference method, the cefixime Etest MIC values were consistently underreported by one dilution (seven laboratories) or two dilutions (one laboratory). The azithromycin Etest MIC values agreed 90.7 % with the agar dilution MIC values while the agreement with ceftriaxone was 90.9 %. CONCLUSION: Overall, the Etest method yielded reproducible MIC values within each laboratory with the azithromycin and ceftriaxone MIC results consistent to the reference agar dilution method while the cefixime result tended to provide a lower MIC value. |
Antimicrobial drug prescription and Neisseria gonorrhoeae susceptibility, United States, 2005-2013
Kirkcaldy RD , Bartoces MG , Soge OO , Riedel S , Kubin G , Del Rio C , Papp JR , Hook EW 3rd , Hicks LA . Emerg Infect Dis 2017 23 (10) 1657-1663 We investigated whether outpatient antimicrobial drug prescribing is associated with Neisseria gonorrhoeae antimicrobial drug susceptibility in the United States. Using susceptibility data from the Gonococcal Isolate Surveillance Project during 2005-2013 and QuintilesIMS data on outpatient cephalosporin, macrolide, and fluoroquinolone prescribing, we constructed multivariable linear mixed models for each antimicrobial agent with 1-year lagged annual prescribing per 1,000 persons as the exposure and geometric mean MIC as the outcome of interest. Multivariable models did not demonstrate associations between antimicrobial drug prescribing and N. gonorrhoeae susceptibility for any of the studied antimicrobial drugs during 2005-2013. Elucidation of epidemiologic factors contributing to resistance, including further investigation of the potential role of antimicrobial drug use, is needed. |
Cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance and decreased ceftriaxone susceptibility, Hawaii, 2016.
Katz AR , Komeya AY , Kirkcaldy RD , Whelen AC , Soge OO , Papp JR , Kersh EN , Wasserman GM , O'Connor NP , O'Brien PS , Sato DT , Maningas EV , Kunimoto GY , Tomas JE . Clin Infect Dis 2017 65 (6) 918-923 Background.: The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We report on a cluster of N. gonorrhoeae isolates demonstrating high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. Methods.: Eight N. gonorrhoeae isolates collected from 7 patients on Oahu seen 21 April through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 mul/mL and elevated ceftriaxone MICs (≥0.125 mug/mL). Isolates were sent to University of Washington and CDC for confirmatory agar dilution testing, and sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. Results.: All isolates had azithromycin MICs >16 microg/mL and 5 had ceftriaxone MICs = 0.125 microg/mL by agar dilution. All isolates were beta-lactamase positive, and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use and no male patients reported male sex partners. All patients were successfully treated. Conclusions.: This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer. |
Population attributable fraction of tubal factor infertility associated with chlamydia
Gorwitz RJ , Wiesenfeld HC , Chen PL , Hammond KR , Sereday KA , Haggerty CL , Johnson RE , Papp JR , Kissin DM , Henning TC , Hook EW 3rd , Steinkampf MP , Markowitz LE , Geisler WM . Am J Obstet Gynecol 2017 217 (3) 336 e1-336 e16 BACKGROUND: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiologic studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared to white women, but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility. OBJECTIVES: To estimate the population attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (black, non-black), and assess how different definitions of C. trachomatis seropositivity and tubal factor infertility affect population attributable fraction estimates. STUDY DESIGN: We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL and Pittsburgh, PA during October 2012 - June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of one and three controls per case for black and non-black women, respectively. We assessed C. trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated C. trachomatis seropositivity and calculated C. trachomatis-TFI odds ratios and population attributable fraction, stratified by race. RESULTS: We enrolled 107 black women (47 cases, 60 controls) and 620 non-black women (140 cases, 480 controls). C. trachomatis seropositivity by either assay was 81% (95% confidence interval 73%, 89%) among black and 31% (95% confidence interval 28%, 35%) among non-black participants (P<0.001). Using the primary C. trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among blacks (odds ratio 1.22, 95% confidence interval 0.45, 3.28) or non-blacks (odds ratio 1.41, 95% confidence interval 0.95, 2.09), and the estimated population attributable fraction was 15% (95% confidence interval -97%, 68%) among blacks and 11% (95% confidence interval -3%, 23%) among non-blacks. Use of alternate serologic measures and tubal factor infertility definitions impacted the magnitude of the chlamydia-tubal factor infertility association, and resulted in a significant association among non-blacks. CONCLUSIONS: Low population attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background C. trachomatis seropositivity among controls, most striking among black participants, could have obscured an association with tubal factor infertility and resulted in a population attributable fraction that underestimates the true etiologic role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also impacts odds ratio and population attributable fraction estimates. |
Azithromycin Resistance and Decreased Ceftriaxone Susceptibility in Neisseria gonorrhoeae, Hawaii, USA.
Papp JR , Abrams AJ , Nash E , Katz AR , Kirkcaldy RD , O'Connor NP , O'Brien PS , Harauchi DH , Maningas EV , Soge OO , Kersh EN , Komeya A , Tomas JE , Wasserman GM , Kunimoto GY , Trees DL , Whelen AC . Emerg Infect Dis 2017 23 (5) 830-832 During 2016, eight Neisseria gonorrhoeae isolates from 7 patients in Hawaii were resistant to azithromycin; 5 had decreased in vitro susceptibility to ceftriaxone. Genomic analysis demonstrated a distinct phylogenetic clade when compared with local contemporary strains. Continued evolution and widespread transmission of these strains might challenge the effectiveness of current therapeutic options. |
Immunoglobulin-based investigation of spontaneous resolution of chlamydia trachomatis infection
Bakshi R , Gupta K , Jordan SJ , Brown LT , Press CG , Gorwitz RJ , Papp JR , Morrison SG , Lee JY , Morrison RP , Geisler WM . J Infect Dis 2017 215 (11) 1653-1656 Chlamydia trachomatis (CT) elementary body (EB) ELISA was used to investigate serum anti-CT IgG1 (long-lived response) and IgG3 (short-lived response indicating more recent infection) from treatment (enrollment) and 6-month follow-up visits in 77 women previously classified as having spontaneous resolution of chlamydia. 71.4% of women were IgG1+IgG3+, consistent with more recent chlamydia resolution. 15.6% were IgG3- at both visits, suggesting absence of recent chlamydia. Using EB ELISA, we demonstrated about one in six women classified as having spontaneous resolution of chlamydia might have been exposed to CT but not infected. Further, we classified their possible infection stage. |
Considerations for strengthening surveillance of Neisseria gonorrhoeae antimicrobial resistance and interpreting surveillance data
Kirkcaldy RD , Schlanger K , Papp JR , Torrone EA . Sex Transm Dis 2017 44 (3) 154-156 Since the introduction of antimicrobials in the first half of the twentieth century, Neisseria gonorrhoeae has repeatedly acquired resistance to the drugs used for treatment. The victims of the bacterium’s relentless acquisition of resistance have included sulfonamides, penicillin, tetracycline, and fluoroquinolones. During the past several years, gonococcal resistance has received substantial attention in the United States. Circulating strains of N. gonorrhoeae have been found to have reduced susceptibility to recommended treatment options, the antibiotic pipeline remains at a trickle, and STD public health programs are stretched increasingly thin as syphilis, chlamydia, and gonorrhea case rates are increasing.[1] Taking its place among the ranks of Clostridium difficile and carbapenem-resistant Enterobacteriaceae, N. gonorrhoeae was labeled an “urgent” antibiotic resistance threat by the Centers for Disease Control and Prevention in 2013.[2] | N. gonorrhoeae antimicrobial resistance is a reminder of our global interconnectedness. Penicillinase-producing N. gonorrhoeae, fluoroquinolone-resistant N. gonorrhoeae, and strains with reduced cephalosporin susceptibility seem to have initially emerged or at least been initially detected in East Asia before being detected in other countries around the world in subsequent years, including the United States.[3–5] In some ways, gonococcal resistance trends and developments in East Asia have served as a canary in a coal mine, allowing us to anticipate possible future developments elsewhere. Thus antimicrobial susceptibility surveillance data from Japan, such as presented in this issue by Yasuda et al, are welcome contributions to our understanding of gonococcal resistance worldwide.[6] |
Comparing the disk-diffusion and agar dilution tests for Neisseria gonorrhoeae antimicrobial susceptibility testing
Liu H , Taylor TH Jr , Pettus K , Johnson S , Papp JR , Trees D . Antimicrob Resist Infect Control 2016 5 46 BACKGROUND: We assessed the validity of testing for antimicrobial susceptibility of clinical and mutant Neisseria gonorrhoeae (GC) isolates by disk diffusion in comparison to agar dilution, and Etest(R) (bioMerieux, France), respectively, for three third generation extended spectrum cephalosporins (ESC): ceftriaxone (CRO), cefixime (CFX), and cefpodoxime (CPD). METHODS: One hundred and five clinical isolates and ten laboratory-mutants were tested following Clinical Laboratory Standard Institute (CLSI) and manufacturer's standards for each of the three methods. The measured diameters by the disk diffusion method were tested for correlation with the MIC values by agar dilution. In addition, comparisons with the Etest(R) were made. Categorical results for concordance, based on standard CLSI cutoffs, between the disk diffusion and the other two methods, respectively, were tested using the Chi-square statistics. Reproducibility was tested for CFX across a 6-month interval by repeated disk tests. RESULTS: Across all 115 specimens, the disk diffusion tests produced good categorical agreements, exhibiting concordance of 93.1%, 92.1%, and 90.4% with agar dilution and 93.0%, 92.1%, and 90.4% with Etest(R), for CRO, CFX, and CPD, respectively. Pearson correlations between disk-diffusion diameters and agar dilution MIC's were -0.59, -0.67, and -0.81 for CRO, CFX, and CPD, respectively. The correlations between disk diffusion and Etest(R) were -0.58, -0.73, and -0.49. Pearson correlation between the CFX disk readings over a 6-month interval was 91%. CONCLUSIONS: Disk diffusion tests remain to be a useful, reliable and fast screening method for qualitative antimicrobial susceptibility testing for ceftriaxone, cefixime, and cefpodoxime. |
In vitro growth of multidrug-resistant Neisseria gonorrhoeae isolates is inhibited by ETX0914, a novel spiropyrimidinetrione
Papp JR , Lawrence K , Sharpe S , Mueller J , Kirkcaldy RD . Int J Antimicrob Agents 2016 48 (3) 328-30 Antimicrobial resistance in Neisseria gonorrhoeae has severely limited the number of treatment options, and the emergence of extended-spectrum cephalosporin resistance threatens the effectiveness of the last remaining recommended treatment regimen. This study assessed the in vitro susceptibility of N. gonorrhoeae to ETX0914, a novel spiropyrimidinetrione that inhibits DNA biosynthesis. In vitro activity was determined by agar dilution against 100 N. gonorrhoeae isolates collected from men presenting with urethritis in the USA during 2012-2013 through the Gonococcal Isolate Surveillance Project. The minimum inhibitory concentration (MIC) that inhibited growth in 50% (MIC50) and 90% (MIC90) of isolates was calculated for each antimicrobial agent. ETX0914 demonstrated a high level of antimicrobial activity against N. gonorrhoeae, including isolates with decreased susceptibility or resistance to currently available agents. The ability of ETX0914 to inhibit the growth of N. gonorrhoeae was similar to ceftriaxone, which is currently recommended in combination with azithromycin to treat gonorrhoea. The data presented in this study strongly suggest that ETX0914 should be evaluated in a clinical trial for the treatment of N. gonorrhoeae. |
Recovery of Neisseria gonorrhoeae from 4 commercially available transport systems
Papp JR , Henning T , Khubbar M , Kalve V , Bhattacharyya S , Travanty E , Xavier K , Jones K , Rudrik JT , Gaynor A , Hagan C . Diagn Microbiol Infect Dis 2016 86 (2) 144-7 Four commercial transport systems for the recovery of Neisseria gonorrhoeae were evaluated in support of the need to obtain culture isolates for the detection of antimicrobial resistance. Bacterial recovery from the InTray GC system was superior with minimal loss of viability in contrast to non-nutritive transport systems. |
Neisseria gonorrhoeae antimicrobial susceptibility surveillance - the Gonococcal Isolate Surveillance Project, 27 Sites, United States, 2014
Kirkcaldy RD , Harvey A , Papp JR , Del Rio C , Soge OO , Holmes KK , Hook EW 3rd , Kubin G , Riedel S , Zenilman J , Pettus K , Sanders T , Sharpe S , Torrone E . MMWR Surveill Summ 2016 65 (7) 1-19 PROBLEM/CONDITION: Gonorrhea is the second most commonly reported notifiable disease in the United States; 350,062 gonorrhea cases were reported in 2014. Sexually transmitted infections caused by Neisseria gonorrhoeae are a cause of pelvic inflammatory disease in women, which can lead to serious reproductive complications including tubal infertility, ectopic pregnancy, and chronic pelvic pain. Prevention of sequelae and of transmission to sexual partners relies largely on prompt detection and effective antimicrobial treatment. However, treatment has been compromised by the absence of routine antimicrobial susceptibility testing in clinical care and evolution of antimicrobial resistance to the antibiotics used to treat gonorrhea. PERIOD COVERED: 2014. DESCRIPTION OF THE SYSTEM: The Gonococcal Isolate Surveillance Project (GISP) was established in 1986 as a sentinel surveillance system to monitor trends in antimicrobial susceptibilities of N. gonorrhoeae strains in the United States. Each month, N. gonorrhoeae isolates are collected from up to the first 25 men with gonococcal urethritis attending each of the participating sexually transmitted disease (STD) clinics at 27 sites. The number of participating sites has varied over time (21-30 per year). Selected demographic and clinical data are abstracted from medical records. Isolates are tested for antimicrobial susceptibility using agar dilution at one of five regional laboratories. RESULTS: A total of 5,093 isolates were collected in 2014. Of these, 25.3% were resistant to tetracycline, 19.2% to ciprofloxacin, and 16.2% to penicillin (plasmid-based, chromosomal, or both). Reduced azithromycin susceptibility (Azi-RS) (defined as minimum inhibitory concentration [MIC] ≥2.0 microg/mL) increased from 0.6% in 2013 to 2.5% in 2014. The increase occurred in all geographic regions, but was greatest in the Midwest, and among all categories of sex of sex partners (men who have sex with men [MSM], men who have sex with men and women [MSMW], and men who have sex with women [MSW]). No Azi-RS isolates exhibited reduced cefixime or ceftriaxone susceptibility (Cfx-RS and Cro-RS, respectively). The prevalence of Cfx-RS (MIC ≥0.25 microg/mL) increased from 0.1% in 2006 to 1.4% in both 2010 and 2011, decreased to 0.4% in 2013, and increased to 0.8% in 2014. Cro-RS (MIC ≥0.125 microg/mL) increased following a similar pattern but at lesser percentages (increased from 0.1% in 2008 to 0.4% in 2011 and decreased to 0.1% in 2013 and 2014). The percentage of isolates resistant to tetracycline, ciprofloxacin, penicillin, or all three antimicrobials, was greater in isolates from MSM than from MSW. INTERPRETATION: This is the first report to present comprehensive surveillance data from GISP and summarize gonococcal susceptibility over time, as well as underscore the history and public health implications of emerging cephalosporin resistance. Antimicrobial susceptibility patterns vary by geographic region within the United States and by sex of sex partner. Because dual therapy with ceftriaxone plus azithromycin is the only recommended gonorrhea treatment, increases in azithromycin and cephalosporin MICs are cause for concern that resistance to these antimicrobial agents might be emerging. It is unclear whether increases in the percentage of isolates with Azi-RS mark the beginning of a trend. The percentage of isolates with elevated cefixime MICs increased during 2009-2010, then decreased during 2012-2013 after treatment recommendations were changed in 2010 to recommend dual therapy (with a cephalosporin and a second antibiotic) and a higher dosage of ceftriaxone. Subsequently, the treatment recommendations were changed again in 2012 to no longer recommend cefixime as part of first-line therapy (leaving ceftriaxone-based dual therapy as the only recommended therapy). Despite the MIC decrease (i.e., trend of improved cefixime susceptibility) during 2012-2013, the increase in the number of strains with Cfx-RS in 2014 underscores the potential threat of cephalosporin-resistant N. gonorrhoeae. PUBLIC HEALTH ACTION: The National Strategy for Combating Antibiotic-Resistant Bacteria identifies prevention, rapid detection, and control of outbreaks of ceftriaxone-resistant N. gonorrhoeae infection as a priority for U.S. PUBLIC HEALTH ACTION: Antimicrobial susceptibility surveillance is conducted to guide development of treatment recommendations for effective therapy and prevention of complications from and transmission of gonorrhea. Federal agencies can use GISP data to develop national treatment recommendations and set research and prevention priorities. Local and state health departments can use GISP data to determine allocation of STD prevention services and resources, guide prevention planning, and communicate best treatment practices to health care providers. Continued surveillance, appropriate treatment, development of new antibiotics, and prevention of transmission remain the best strategies to reduce gonorrhea incidence and morbidity. |
Trends in Neisseria gonorrhoeae susceptibility to cephalosporins in the United States, 2006-2014
Kirkcaldy RD , Hook EW 3rd , Soge OO , del Rio C , Kubin G , Zenilman JM , Papp JR . JAMA 2015 314 (17) 1869-71 Gonorrhea is a common sexually transmitted disease that, if untreated, can cause reproductive health complications. Gonorrhea treatment has been repeatedly jeopardized by antimicrobial resistance. To ensure effective treatment, the Centers for Disease Control and Prevention (CDC) periodically updates treatment guidelines based on resistance trends. In 2010 and following declining cephalosporin susceptibility in several countries, CDC updated its treatment recommendation from single-dose cephalosporin (injectable ceftriaxone or oral cefixime) to intensified combination therapy of either ceftriaxone (at a higher dose than previously recommended) or cefixime, plus a second antimicrobial.1 CDC again updated guidelines in 2012 to recommend ceftriaxone-based combination therapy as the single recommended therapy.1 We describe recent gonococcal cephalosporin susceptibility trends emphasizing changes following publication of these guidelines. |
Comparison of antimicrobial susceptibility of urogenital Neisseria gonorrhoeae isolates obtained from women and men
Kidd S , Moore PC , Kirkcaldy RD , Philip SS , Wiesenfeld HC , Papp JR , Kerndt PR , Venkatasubramanian L , Ghanem KG , Hook EW 3rd . Sex Transm Dis 2015 42 (8) 434-9 BACKGROUND: The US system for gonococcal antimicrobial susceptibility surveillance monitors trends exclusively among men with urethral infection, the population from whom the yield of gonococcal culture is highest. Little is known about the susceptibility of female urogenital isolates, and it is unclear whether gonococcal susceptibility among men who report sex exclusively with women (MSW) is representative of susceptibility among women. METHODS: Using isolates collected during a recent treatment trial in 5 US cities, we performed a secondary analysis to compare antimicrobial susceptibilities of Neisseria gonorrhoeae urogenital isolates obtained from women, MSW, and men who have sex with men (MSM). Pretreatment isolates were collected from trial participants; minimum inhibitory concentrations (MICs) were determined by agar dilution. Geometric mean MICs were adjusted for geographic location using general linear models. RESULTS: Susceptibility data for urogenital isolates from 56 women, 252 MSW, and 170 MSM were studied. The adjusted geometric mean ceftriaxone MIC was similar among women (0.0067 mug/mL; 95% confidence interval [CI], 0.0049-0.0092 mug/mL) and MSW (0.0060 mug/mL; 95% CI, 0.0053-0.0066 mug/mL). In contrast, the adjusted geometric mean ceftriaxone MIC was higher among MSM (0.0098 mug/mL; 95% CI, 0.0082-0.0119 mug/mL) than among MSW. This same pattern was observed for other antimicrobials, including cefixime and azithromycin CONCLUSIONS: Ceftriaxone, cefixime, and azithromycin MICs were higher among MSM than among MSW, but were similar among women and MSW. These findings suggest that gonococcal antimicrobial susceptibility surveillance based on urethral isolates from MSW may adequately represent susceptibility of urogenital N. gonorrhoeae in women. |
Analysis of Neisseria gonorrhoeae azithromycin susceptibility in the United States by the Gonococcal Isolate Surveillance Project, 2005 to 2013
Kirkcaldy RD , Soge O , Papp JR , Hook EW 3rd , Del Rio C , Kubin G , Weinstock HS . Antimicrob Agents Chemother 2014 59 (2) 998-1003 BACKGROUND: Azithromycin, administered with ceftriaxone, is recommended by CDC for treatment of gonorrhea. Many experts have expressed concern about the ease with which Neisseria gonorrhoeae can acquire macrolide resistance. OBJECTIVE: We sought to describe gonococcal azithromycin susceptibility in the United States and determine whether azithromycin susceptibility has changed over time. METHODS: We analyzed 2005-2013 data from the Gonococcal Isolate Surveillance Project, a CDC-supported sentinel surveillance network that monitors gonococcal antimicrobial susceptibility. RESULTS: 44,144 N. gonorrhoeae isolates were tested for azithromycin susceptibility by agar dilution methods. The overall azithromycin MIC50 was 0.25 mug/ml and the MIC90 was 0.5 mug/ml. There were no overall temporal trends in geometric means. Isolates from men who had sex with men had significantly higher geometric mean MICs than isolates from men who have sex exclusively with women. The overall prevalence of reduced azithromycin susceptibility (MIC ≥2 mug/ml) was 0.4% and varied by year from 0.3% (2006 and 2009) to 0.6% (2013). CONCLUSION: We did not find a clear temporal trend in gonococcal azithromycin MICs in the United States and the prevalence of reduced azithromycin susceptibility remains low. These findings support continued use of azithromycin in the combination therapy regimen for gonorrhea. |
The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea
Kirkcaldy RD , Weinstock HS , Moore PC , Philip SS , Wiesenfeld HC , Papp JR , Kerndt PR , Johnson S , Ghanem KG , Hook EW 3rd . Clin Infect Dis 2014 59 (8) 1083-91 BACKGROUND: Ceftriaxone is the foundation of currently recommended gonorrhea treatment.There is an urgent need for back-up treatment options for patients withcephalosporin-allergy or infections due to suspected cephalosporin-resistant Neisseria gonorrhoeae. We evaluated the efficacy and tolerability of two combinations of existing non-cephalosporin antimicrobials for treatment of patients with urogenital gonorrhea. METHODS: We conducted a randomized, multisite,open-label, non-comparative trial (ClinicalTrials.gov:NCT00926796) in 5 outpatient sexually transmitted disease clinic sites in Alabama, California, Maryland and Pennsylvania. Patients aged 15-60 years diagnosed with uncomplicated urogenital gonorrhea were randomly assigned to either gentamicin 240 mg intramuscularly plus azithromycin 2 g orally, or gemifloxacin 320 mg orally plus azithromycin 2 g orally. The primary outcome was microbiological cure of urogenital infections (negative follow-up culture) at 10-17 days post-treatment among 401 participants in the per protocol population. RESULTS: Microbiological cure was achieved by 100% (lower one-sided exact 95% confidence interval bound, 98.5%) of 202 evaluable participants receiving gentamicin/azithromycin, and 99.5% (lower one-sided exact 95% confidence interval bound, 97.6%) of 199 evaluable participants receiving gemifloxacin/azithromycin. Gentamicin/azithromycin cured 10/10 pharyngeal infections and 1/1 rectal infection; gemifloxacin/azithromycin cured 15/15 pharyngeal and 5/5 rectal infections. Gastrointestinal adverse events were common in both arms. CONCLUSION: Gentamicin/azithromycin and gemifloxacin/azithromycin were highly effective for treatment of urogenital gonorrhea. Gastrointestinal adverse events may limit routine use. These non-cephalosporin-based regimens may be useful alternative options for patients who cannot be treated with cephalosporin antimicrobials. Additional treatment options for gonorrhea are needed. |
Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae - 2014
Papp JR , Schachter J , Gaydos CA , Van Der Pol B . MMWR Recomm Rep 2014 63 1-19 This report updates CDC's 2002 recommendations regarding screening tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections (CDC. Screening tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections-2002. MMWR 2002;51[No. RR-15]) and provides new recommendations regarding optimal specimen types, the use of tests to detect rectal and oropharyngeal C. trachomatis and N. gonorrhoeae infections, and circumstances when supplemental testing is indicated. The recommendations in this report are intended for use by clinical laboratory directors, laboratory staff, clinicians, and disease control personnel who must choose among the multiple available tests, establish standard operating procedures for collecting and processing specimens, interpret test results for laboratory reporting, and counsel and treat patients. The performance of nucleic acid amplification tests (NAATs) with respect to overall sensitivity, specificity, and ease of specimen transport is better than that of any of the other tests available for the diagnosis of chlamydial and gonococcal infections. Laboratories should use NAATs to detect chlamydia and gonorrhea except in cases of child sexual assault involving boys and rectal and oropharyngeal infections in prepubescent girls and when evaluating a potential gonorrhea treatment failure, in which case culture and susceptibility testing might be required. NAATs that have been cleared by the Food and Drug Administration (FDA) for the detection of C. trachomatis and N. gonorrhoeae infections are recommended as screening or diagnostic tests because they have been evaluated in patients with and without symptoms. Maintaining the capability to culture for both N. gonorrhoeae and C. trachomatis in laboratories throughout the country is important because data are insufficient to recommend nonculture tests in cases of sexual assault in prepubescent boys and extragenital anatomic site exposure in prepubescent girls. N. gonorrhoeae culture is required to evaluate suspected cases of gonorrhea treatment failure and to monitor developing resistance to current treatment regimens. Chlamydia culture also should be maintained in some laboratories to monitor future changes in antibiotic susceptibility and to support surveillance and research activities such as detection of lymphogranuloma venereum or rare infections caused by variant or mutated C. trachomatis. |
Trends in antimicrobial resistance in Neisseria gonorrhoeae in the USA: the Gonococcal Isolate Surveillance Project (GISP), January 2006-June 2012
Kirkcaldy RD , Kidd S , Weinstock HS , Papp JR , Bolan GA . Sex Transm Infect 2013 89 Suppl 4 iv5-iv10 BACKGROUND: Neisseria gonorrhoeae has progressively developed resistance to sulfonamides, penicillin, tetracycline and fluoroquinolones, and gonococcal susceptibility to cephalosporins has been declining worldwide. METHODS: We described trends in gonococcal antimicrobial susceptibility in the USA from January 2006 through June 2012. Susceptibility data for cefixime, ceftriaxone, azithromycin, penicillin, tetracycline and ciprofloxacin were obtained from the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance system that monitors antimicrobial susceptibility in urethral gonococcal isolates collected from symptomatic men at 25-30 sexually transmitted disease clinics throughout the USA. RESULTS: The percentage of isolates with elevated cefixime minimum inhibitory concentrations (MICs) (≥0.25 microg/mL) increased from 0.1% in 2006 to 1.4% in 2010-2011 and was 1.1% in the first 6 months of 2012. The percentage with elevated ceftriaxone MICs (≥0.125 microg/mL) increased from 0.1% in 2006 to 0.3%-0.4% during 2009 through the first 6 months of 2012. There were no temporal trends in the prevalence of elevated azithromycin MICs (≥2 microg/mL) (0.2%-0.5%). The prevalence of resistance remained high for penicillin (11.2%-13.2%), tetracycline (16.7%-22.8%) and ciprofloxacin (9.6%-14.8%). CONCLUSIONS: The proportion of gonococcal isolates with elevated cephalosporin MICs increased from 2006 to 2010, but plateaued during 2011 and the first 6 months of 2012. Resistance to previously recommended antimicrobials has persisted. As the number of antimicrobials available for gonorrhoea treatment dwindles, surveillance systems such as GISP will be critical to detect emerging resistance trends and guide treatment decisions. |
Prevalence of Neisseria gonorrhoeae among persons 14 to 39 years of age, United States, 1999 to 2008
Torrone EA , Johnson RE , Tian LH , Papp JR , Datta SD , Weinstock HS . Sex Transm Dis 2013 40 (3) 202-5 BACKGROUND: Prevalence estimates from population-based surveys do not suffer from the same biases as case-report and clinic positivity data and may be better to monitor sexually transmitted disease morbidity over time. METHODS: We estimated the prevalence of Neisseria gonorrhoeae in a nationally representative sample of persons aged 14 to 39 years participating in the National Health and Nutrition Examination Survey. RESULTS: From 1999 to 2008, the overall prevalence of gonorrhea was 0.27% (95% confidence interval, 0.13%-0.47%). In the 2005 to 2006 and 2007 to 2008 cycles, prevalence approached 0% and was based on too few positive sample persons to obtain reliable estimates. In 2004, most infections were found in 1 survey location. DISCUSSION: Given the low prevalence and geographic clustering of disease, gonorrhea estimates from national probability surveys are often imprecise and unstable. In 2008, gonorrhea testing in National Health and Nutrition Examination Survey was discontinued. Continued surveillance of gonorrhea should include case reporting and prevalence estimates from local surveys and sentinel surveillance systems. |
Nucleic acid amplification tests for the diagnosis of neisseria gonorrhoeae and chlamydia trachomatis rectal infections
Bachmann LH , Johnson RE , Cheng H , Markowitz L , Papp JR , Palella FJ Jr , Hook 3rd EW . J Clin Microbiol 2010 48 (5) 1827-32 Optimal methods for the diagnosis of rectal gonococcal and chlamydial infection are uncertain. This study evaluated performance of culture and nucleic acid amplification tests (NAATs) for rectal chlamydial and gonococcal diagnosis. From July 2003 until February 2007, 441 rectal test sets were collected from individuals attending a sexually transmitted disease clinic and 3 HIV clinics who gave a history of anal intercourse or were women at high risk for N. gonorrhoeae or C. trachomatis infections. Rectal swab specimens were tested using culture and commercial NAATs employing Transcription Mediated Amplification (TMA), Strand Displacement Amplification (SDA), and Polymerase Chain Reaction (PCR) Amplification. Test performance was evaluated using a rotating standard by which patients were classified infected if either two or three comparator tests were positive. Test sensitivities for the detection of N. gonorrhoeae ranged from 66.7% to 71.9% for culture to 100% for TMA. Specificities were 99.7% to 100% for culture and greater than 95.5% for all 3 NAATs. Test sensitivities for C. trachomatis ranged from 36.1% to 45.7% for culture and among NAATS from 91.4% to 95.8% for PCR to 100% for TMA. Specificities of the NAATs ranged from 95.6% to 98.5% (2 of 3 standard) and from 88.8% to 91.8% (3 of 3 standard). Over 60% and 80% of gonococcal and chlamydial infections among men who have sex with men and over 20% of chlamydial infections in women, respectively, would have been missed if the rectal site had not been tested. Currently available NAATs are more sensitive than culture for detection of chlamydial and gonococcal infection at the rectal site. |
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