Azithromycin Susceptibility Research Articles

Remarkable increase of Neisseria gonorrhoeae with decreased susceptibility of azithromycin and increase in the failure of azithromycin therapy in male gonococcal urethritis in Sendai in 2015.

The antimicrobial resistance of Neisseria gonorrhoeae is a serious problem worldwide. In this study, we examined the susceptibility of N. gonorrhoeae isolated from male gonococcal urethritis in Sendai in 2014 and 2015. Furthermore, of all cases, we investigated the clinical efficacy of a single 2-g dose of extended-release azithromycin (AZM-SR) in the treatment of male gonococcal urethritis retrospectively. Sixty N. gonorrhoeae strains in 2014 and 54 strains in 2015 were isolated from male gonococcal urethritis and stored each year. The MIC of AZM was ≥1mg/L in 4 strains (6.7%) in 2014 and in 13 strains (24.1%) in 2015 and the number of strains having ≥1mg/L MIC increased significantly (P=0.016). Microbiological efficacy was evaluated in 32 and 29 of these patients, and the rates of treatment success were 93.8% and 79.3%, respectively. All of the treatment failures were caused by strains having a MIC of AZM of ≥0.5mg/L. In particular, the increase in the isolates having a MIC of AZM of ≥1mg/L was remarkable. Therefore, it was thought that the increase in these strains was the reason for the increase in treatment failures in 2015. Because no other drug is effective, it is currently necessary to use AZM-SR to treat gonococcal infections caused by ceftriaxone-resistant strains or patients allergic to ceftriaxone. To prevent a further increase in resistance to AZM, we should not use AZM-SR to treat normal cases of gonococcal infection.

Neisseria gonorrhoeae Antimicrobial Susceptibility Surveillance - The Gonococcal Isolate Surveillance Project, 27 Sites, United States, 2014.

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. 2014. 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. 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 µg/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 µg/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 µg/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. 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. 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. 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.

Results from the Survey of Antibiotic Resistance (SOAR) 2009-11 in Vietnam.

To investigate the susceptibility of respiratory tract infection pathogens collected between 2009 and 2011 from the SOAR study in Vietnam. MICs were determined using Etest(®) and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Two hundred and eighty-nine Streptococcus pneumoniae and 195 Haemophilus influenzae were collected from 11 centres. Overall, 4.8% of S. pneumoniae were penicillin susceptible (CLSI oral and EUCAST breakpoints). Using CLSI intravenous breakpoints, 86.9% were penicillin susceptible. Susceptibility to high-dose amoxicillin/clavulanic acid (or amoxicillin) using PK/PD breakpoints, cefuroxime (using CLSI or PK/PD breakpoints), cefaclor (CLSI breakpoint) and azithromycin (CLSI breakpoint) was 96.9%, 18.7%, 8% and 4.2%, respectively. Ofloxacin susceptibility was 93.4% by CLSI but 0% by EUCAST. All S. pneumoniae were fully vancomycin susceptible. S. pneumoniae from children were significantly less susceptible to most antimicrobials than those from the elderly. For ofloxacin, however, the reverse was true.Among H. influenzae isolates, 40.5% produced β-lactamase and 13.8% were β-lactamase negative but ampicillin resistant (BLNAR) by CLSI. H. influenzae were highly susceptible (97.4%) in vitro to amoxicillin/clavulanic acid and also to ceftriaxone by CLSI and PK/PD breakpoints but not EUCAST breakpoints. However, BLNAR isolates should be considered clinically resistant, with susceptibility reduced to 84.1%. With EUCAST breakpoints, amoxicillin/clavulanic acid susceptibility was lower, at 63.1%. Azithromycin susceptibility was 79.5% (CLSI). Resistance to antibacterials in Vietnam was high, with amoxicillin/clavulanic acid being the most active agent. Ceftriaxone was highly active against H. influenzae while ofloxacin appeared highly active against S. pneumoniae using CLSI but not by EUCAST breakpoints. Ongoing surveillance through SOAR will further assist in understanding susceptibility trends over time.

Azithromycin-Nonsusceptible Shigella flexneri 3a in Men Who Have Sex with Men, Taiwan, 2015-2016.

We report an outbreak of azithromycin-nonsusceptible Shigella flexneri 3a infection in Taiwan associated with men who have sex with men. The bacterial strains belonged to the sublineage A of a recently reported outbreak lineage associated with men who have sex with men, characterized by reduced azithromycin susceptibility and circulation in shigellosis low-risk regions.

Azithromycin Dose To Maximize Efficacy and Suppress Acquired Drug Resistance in Pulmonary Mycobacterium avium Disease.

Mycobacterium aviumcomplex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonaryM. aviumdisease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses.

100 Macrolide resistance is common among members of the CF airway microbiota

Objectives Chronic use of azithromycin has been associated with increased macrolide resistance in recognised CF pathogens. The aims of this study were to determine 1.macrolide resistance amongst other members of the CF airway microbiota 2.if resistance is associated with current patient prescription of azithromycin. Methods The susceptibility (MIC) of CF respiratory isolates (n = 26: Streptococcus, n=8; Rothia, n=5; Veillonella, n=5; Prevotella, n=4; Actinomyces, n=3; Fusobacterium , n=1) to azithromycin, clarithromycin and erythromycin was determined by Etest®. Isolates were separated into two groups depending on whether they were isolated from CF patients currently prescribed or not currently prescribed azithromycin and macrolide susceptibility was compared between the groups using the Mann–Whitney test. Results High-level macrolide resistance (>256 mg/mL) was common among the isolates tested: azithromycin, n=10/26 (38%); clarithromycin, n=6/26 (23%); erythromycin, n=11/26 (42%). Isolates from CF patients currently prescribed azithromycin (n = 9) had significantly higher MICs for the three macrolide antibiotics compared to isolates from patients not prescribed azithromycin (n = 17) [Table]. TableAzithromycin prescription versus susceptibilityMIC50 (mg/mL)PCurrent prescription of azithromycin (n = 9)No current prescription of azithromycin (n = 17)Azithromycin>25620.005Clarithromycin470.50.001Erythromycin>25640.01 Conclusion Resistance to three different macrolide antibiotics was common in bacteria present in the CF airway microbiota and was associated with current azithromycin prescription in CF patients. Work supported by a Wellcome Trust (FA) Vacation Scholarship.

Virulence factors and mechanisms of antimicrobial resistance in Shigella strains from periurban areas of Lima (Peru)

The study was aimed to describe the serotype, mechanisms of antimicrobial resistance, and virulence determinants in Shigella spp. isolated from Peruvian children. Eighty three Shigella spp. were serogrouped and serotyped being established the antibiotic susceptibility. The presence of 12 virulence factors (VF) and integrase 1 and 2, along with commonly found antibiotic resistance genes was established by PCR. S. flexneri was the most relevant serogroup (55 isolates, 66%), with serotype 2a most frequently detected (27 of 55, 49%), followed by S. boydii and S. sonnei at 12 isolates each (14%) and S. dysenteriae (four isolates, 5%).Fifty isolates (60%) were multi-drug resistant (MDR) including 100% of S. sonnei and 64% of S. flexneri. Resistance levels were high to trimethoprim-sulfamethoxazole (86%), tetracycline (74%), ampicillin (67%), and chloramphenicol (65%). Six isolates showed decreased azithromycin susceptibility. No isolate was resistant to nalidixic acid, ciprofloxacin, nitrofurantoin, or ceftriaxone. The most frequent resistance genes were sul2 (95%), tet(B) (92%), cat (80%), dfrA1 (47%), blaOXA-1 like (40%), with intl1 and intl2 detected in 51 and 52% of the isolates, respectively. Thirty-one different VF profiles were observed, being the ipaH (100%), sen (77%), virA and icsA (75%) genes the most frequently found. Differences in the prevalence of VF were observed between species with S. flexneri isolates, particularly serotype 2a, possessing high numbers of VF. In conclusion, this study highlights the high heterogeneity of Shigella VF and resistance genes, and prevalence of MDR organisms within this geographic region.

Acquired macrolide resistance genes in Haemophilus influenzae?

The objective of this study was to determine the prevalence of specific acquired macrolide resistance genes previously reported as present in clinical isolates of Haemophilus influenzae. A collection of 172 clinical respiratory isolates of H. influenzae, including 59 isolates from cystic fibrosis patients and 27 from non-cystic fibrosis bronchiectasis patients with significant prior macrolide use, was established. This collection was tested for azithromycin susceptibility using Etest and screened for the presence of erm(A), erm(B), erm(C), erm(F), mef(A) and mef(E) using locked nucleic acid dual-labelled hydrolysis probes. The azithromycin MICs ranged from 0.09 to >256 mg/L, with 2 (1.2%) isolates susceptible, 163 (94.8%) intermediate and 7 (4%) resistant according to EUCAST breakpoints (susceptible, ≤0.12 mg/L; resistant, >4 mg/L). None of the acquired macrolide resistance genes erm(A), erm(B), erm(C), erm(F), mef(A) or mef(E) was detected in any of the isolates. The specific acquired macrolide resistance genes are not widespread in H. influenzae and the high prevalence of these genes previously reported might be unique to the specific circumstances of that study.

Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A.

Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥13 mm to a 5-μg azithromycin disk identified S. Typhi isolates with an MIC of ≤16 μg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤16 μg/ml or disk inhibition zone size of ≥13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A.

Relationship between azithromycin susceptibility and administration efficacy for nontypeable Haemophilus influenzae respiratory infection.

Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection.

Screening of MDR-bacteria from fecal specimens of AAD patient and inhibit them using fruits extracts of Moringa oleifera Lam

The present research was undertaken to screen of multidrug resistant bacteria (MDRB) from fecal specimens of Antibiotic-associated diarrhea patient and to evaluate the potentiality of M. oleifera fruits extracts on those bacteria with the view to provide scientific evidence for its application in health remedy. MDRB were determined by antibiotic (tetracycline, azithromycin, ciprofloxacin & erythromycin) susceptibility test, using disc-agar diffusion method. Biochemical tests of the MDRB were done according to Bergey’s Manual of Determinative Bacteriology for identification of the species. Minimum inhibitory concentration (MIC) as well as minimum bactericidal concentration (MBC) of the extracts was also measured. Among the 13 isolated bacteria only 5 were found resistant to multiple antibiotics. The fruit extract showed a broad-spectrum antibacterial activity against isolated four species (Escherichia coli, Shigella sp., Salmonella sp. & Klebsiella sp.) of MDRB. Among used two solvents, methanol possessed better antibacterial activity than ethanol. The highest zone of inhibition (19.86mm) was found in methanol at the concentration of 500mg/ml for E. coli. The MIC and MBC values were determined as 300mg/ml and 400mg/ml respectively. The consequences of this investigation suggest that the extracts of M. oleifera Lam. can be used to discover antibacterial agent for developing new pharmaceuticals to control different severe illness caused by MRD bacteria.

Analysis of Neisseria gonorrhoeae azithromycin susceptibility in the United States by the Gonococcal Isolate Surveillance Project, 2005 to 2013.

Azithromycin, administered with ceftriaxone, is recommended by the CDC for the treatment of gonorrhea. Many experts have expressed concern about the ease with which Neisseria gonorrhoeae can acquire macrolide resistance. We sought to describe gonococcal azithromycin susceptibility in the United States and to determine whether azithromycin susceptibility has changed over time. We analyzed data from 2005 to 2013 from the Gonococcal Isolate Surveillance Project, a CDC-supported sentinel surveillance network that monitors gonococcal antimicrobial susceptibility. A total of 44,144 N. gonorrhoeae isolates were tested for azithromycin susceptibility by agar dilution methods. The overall azithromycin MIC50 was 0.25 μg/ml, and the MIC90 was 0.5 μg/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 had sex exclusively with women. The overall prevalence of reduced azithromycin susceptibility (MIC, ≥2 μg/ml) was 0.4% and varied by year from 0.3% (2006 and 2009) to 0.6% (2013). 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 the continued use of azithromycin in a combination therapy regimen for gonorrhea.

A study of antibiogram of Salmonella enterica serovar Typhi isolates from Pondicherry, India.

Enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi) is an important public health problem in developing countries like India.1 The emergence of resistance to fluoroquinolones has reduced the therapeutic options available. Currently, the uniform laboratory interpretation of ciprofloxacin and azithromycin susceptibility remains unclear. To study the antibiogram of S. Typhi isolates with special emphasis on in-vitro activity of ciprofloxacin and azithromycin. We evaluated the antimicrobial susceptibility pattern of 16 S. Typhi isolates from January 2012 to June 2013. We also determined by Epsilometer-test (E-test) method, the minimum inhibitory concentration (MIC) of ciprofloxacin and azithromycin against these isolates and compared them with their corresponding disc diffusion sizes. Fifteen (93.75 per cent) isolates were sensitive to chloramphenicol, 14 (87.5 per cent) were sensitive to cotrimoxazole. All isolates were resistant to nalidixic acid. MICs for ciprofloxacin ranged from 6μg/ml to 15μg/ml and corresponding zone diameters ranged from 15mm to 26mm. MIC and zone diameters for ciprofloxacin had significant negative correlation. MICs for azithromycin ranged from 3μg/ml to 24μg/ml, corresponding zone diameters ranged from 13mm to 19mm. However, MIC and zone diameters for azithromycin had no significant negative correlation. The widespread emergence of resistance to fluoroquinolones and reappearance of sensitivity to firstline drugs has reinforced the need for antibiotic recycling. There is a need to have uniform laboratory testing guidelines for testing susceptibility to ciprofloxacin and azithromycin for S. Typhi isolates.

Shigella spp. with reduced azithromycin susceptibility, Quebec, Canada, 2012-2013.

During 2012–2013 in Montreal, Canada, 4 locally acquired Shigella spp. pulse types with the mph(A) gene and reduced susceptibility to azithromycin were identified from 9 men who have sex with men, 7 of whom were HIV infected. Counseling about prevention of enteric sexually transmitted infections might help slow transmission of these organisms.

P3.278 Azithromycin Susceptibilities in Canadian Neisseria Gonorrhoeae Isolates (2010–2011)

BackgroundNeisseria gonorrhoeae have developed resistance to many antibiotics and current Canadian STI guidelines recommend azithromycin as part of a combination therapy for gonorrhoea.MethodsBetween 2010 and 2011, N. gonorrhoeae strains were...

O18.1 Molecular Techniques For Differentiation of the T. Pallidum Subspecies and Specimen Collection with FTA Elute Cards

IntroductionThe causative agents of venereal syphilis ( Treponema subsp. pallidum), yaws (subsp. pertenue), and bejel (subsp. endemicum) are indistinguishable on the basis of morphology, syphilis serology and existing diagnostic PCR....

With Reduced Azithromycin Susceptibility in the U.S.

Shigellosis is the third most common enteric bacterial infection in the U.S., with incidence highest among children aged <5 years. Infection can spread

Cephalosporin and Azithromycin Susceptibility in Neisseria gonorrhoeae Isolates by Site of Infection, British Columbia, 2006 to 2011

Widespread resistance of Neisseria gonorrhoeae to penicillin, tetracycline, and fluoroquinolones has challenged effective treatment and control; recent international case reports of cefixime, ceftriaxone, and azithromycin resistance suggest that the remaining treatment options are now additionally threatened. To explore trends in antimicrobial susceptibility of N. gonorrhoeae, we reviewed provincial laboratory data from British Columbia, 2006 to 2011. Susceptibility testing was performed for all N. gonorrhoeae isolates detected in-house or forwarded to the reference laboratory. Resistance or intermediate resistance (nonsusceptibility) was defined by standard breakpoints for penicillin, tetracycline, ciprofloxacin, and spectinomycin. Elevated minimum inhibitory concentrations (MICs) at serial dilutions of 0.064 μg/mL or greater were explored for cefixime/ceftriaxone and 0.5 μg/mL or greater for azithromycin. Nonsusceptibility/elevated MIC was compared by year, site of infection, sex, and age. A total of 1837 isolates representing 22% of all reported gonorrhea cases were analyzed. Nonsusceptibility to penicillin was established at baseline. Nonsusceptibility to tetracycline and ciprofloxacin increased over the study period, reaching 96% and 36%, respectively, in 2011. Sixteen isolates (1%) had a cefixime MIC of 0.25 μg/mL (none ≥0.5), none had a ceftriaxone MIC of 0.25 μg/mL or greater, and 15 (1%) had an azithromycin MIC of 2.0 μg/mL or greater. Elevated MIC of these agents showed an increasing trend over time. Nonsusceptibility and elevated MIC were consistently highest at the rectal and pharyngeal sites and higher in isolates from males, including when stratified to the pharyngeal site. Increases in elevated MIC of cefixime/ceftriaxone/azithromycin were superimposed on a background of established resistance to penicillin, tetracycline, and ciprofloxacin and may signal impending gonococcal resistance to first-line treatments. Ongoing surveillance will inform timely shifts in treatment recommendations.

Multiplex Bead Suspension Array for Screening Neisseria gonorrhoeae Antibiotic Resistance Genetic Determinants in Noncultured Clinical Samples

The increasing threat of antibiotic-resistant Neisseria gonorrhoeae highlights the need for new diagnostic options. A high-throughput multiplex bead suspension array assay was developed for profiling 29 N. gonorrhoeae genomic mutations and 2 plasmid genes conferring resistance to 6 antimicrobial agents: penicillin, ciprofloxacin, cefixime, tetracycline, azithromycin, and spectinomycin. The three steps of this assay include amplification of 12 N. gonorrhoeae chromosomal and plasmid loci, multiplex allele-specific primer extension reaction, and multiplex bead suspension array detection. Antibiotic resistance genetic determinants were identified successfully in 239 cervicovaginal N. gonorrhoeae-positive noncultured swab samples. This molecular assay can be used for detection of gonococci in clinical specimens, molecular typing, mutation profiling, and predictive assessment of N. gonorrhoeae susceptibility to antibiotics without the need for culture.

Resistance to Azithromycin of Neisseria gonorrhoeae Isolates From 2 Cities in China

Antimicrobial resistance in Neisseria gonorrhoeae (NG) is a public health concern globally, and azithromycin-resistant NG isolates have been identified in many countries. This study aimed to investigate azithromycin susceptibility in NG and to genetically characterize the azithromycin-resistant isolates identified in 2 cities in China. NG isolates (n = 318) were cultured from patients attending 2 sexually transmitted infection clinics in Nanjing and Chongqing, China, between 2008 and 2009. Minimum inhibitory concentration (MIC) of azithromycin, tetracycline, ciprofloxacin, spectinomycin and ceftriaxone was determined using the agar dilution method. NG strains ATCC 49226 and WHO G, J, L, and P were used for quality control. Azithromycin-resistant isolates were defined as having an MIC value equal to or greater than that of strain WHO P, which is internationally recognized as azithromycin-resistant (MIC = 2 mg/L), and genotyped using NG multiantigen sequence typing. The MIC values of strain WHO P for azithromycin were 2 to 4 mg/L in all runs, which showed that the method provided consistent and reliable MIC values. Seventeen isolates (5.3%) showed resistance to azithromycin. Among these isolates (n = 17), 11 sequence types (STs) were identified by NG multiantigen sequence typing, of which 5 were novel. The most common ST was ST3356, represented by 6 isolates. ST1866 was represented by 2 isolates, which were isolated from patients with an unknown relationship, and both isolates were highly resistant to azithromycin, i.e., displayed an MIC of >64 mg/L. A relatively high prevalence of azithromycin-resistant NG strains implies that azithromycin should not be recommended for the treatment of gonococcal urethritis or cervicitis in China.