Retrospective analysis of antimicrobial susceptibility trends (2000-2009) in Neisseria gonorrhoeae isolates from countries in Latin America and the Caribbean shows evolving resistance to ciprofloxacin, azithromycin and decreased susceptibility to ceftriaxone.

BACKGROUND: The emergence of resistance and treatment failures to third generation cephalosporins prompted the revitalization of the global Gonococcal Antimicrobial Surveillance Program (GASP) to ensure that information regarding trends of the antimicrobial susceptibility of Neisseria gonorrhoeae isolates is up-to-date. Accordingly, former and potential GASP participants in Latin America and the Caribbean were contacted to reinitiate the GASP network in the region and to undertake a retrospective analysis of the antimicrobial susceptibility of N. gonorrhoeae isolates between 2000 and 2009. METHODS: Eleven countries participated in this retrospective analysis reporting on the susceptibility of N. gonorrhoeae isolates to up to 6 antibiotics as well as national treatment guidelines over the period. Antimicrobial susceptibility determination was carried out using combination of agar dilution and disk diffusion (Clinical Laboratory and Standards Institute) or Etest. Antimicrobial susceptibility data from each country were aggregated and analyzed for antimicrobial resistance trends in the region. RESULTS: More than 11,400 N. gonorrhoeae isolates were tested for antimicrobial susceptibility: 6 countries tested N. gonorrhoeae over the entire period and 5 countries tested sporadically. Decreased susceptibility to ceftriaxone was reported from 1 country (7 isolates, MICs >0.25 µg/ml) in 2007. No resistance to spectinomycin was reported. From 2000 to 2009, aggregated ciprofloxacin resistance increased from 2% (19/784) to 31% (311/1015) in 9 countries and azithromycin resistance increased from 6% (39/646) to 23% (225/962) in 4/6 reporting countries. Overall, resistance to penicillin and tetracycline decreased from 35% (441/1241) to 26% (258/975) and from 60% (476/792) to 35% (323/931), respectively.In 2009, resistance to gentamicin (3%, 4/122), chloramphenicol (5%, 6/120), and ofloxacin (2%, 6/120) was reported from 1 country. CONCLUSIONS: The report of ceftriaxone-resistant isolates coupled with the emergence and spread of resistance to ciprofloxacin and azithromycin in Latin America and the Caribbean in the 2000s indicates the importance of active surveillance of N. gonorrhoeae antimicrobial susceptibility to determine antimicrobial resistance emerging trends so as to promptly inform and guide the development of effective treatment options for gonococcal infections.

Epidemic methicillin-susceptible Staphylococcus aureus lineages are the main cause of infections at an Iranian university hospital.

The majority of Staphylococcus aureus infections from Isfahan, Iran, were caused by epidemic methicillin-susceptible S. aureus (MSSA) lineages, sequence type 8 (ST8), ST22, ST30, and ST6. The predominant methicillin-resistant S. aureus strain was ST239. We observed a high prevalence of Panton-Valentine leukocidin-positive MSSA strains (19.7%), which is a matter of considerable concern, since these strains have the ability to cause severe infections.

Circulating levels of interleukin-17A and interleukin-23 are increased in patients with gonococcal infection.

Neisseria gonorrhoeae is the etiological agent of gonorrhoea, an infectious disease characterized by acute inflammation of the urogenital tract with a massive infiltration of neutrophils. Polymorphonuclear leukocyte recruitment is one of the activities of the recently described interleukin-17A (IL-17A); thus, we analyzed the serum concentration of IL-17A, together with IL-23 and interferon-γ (IFN-γ), in 27 patients with gonorrhoea. The concentration of these cytokines in patients' sera was significantly higher than that detected in healthy controls and an inverse correlation was found between the concentrations of IL-17A and IFN-γ. This is the first report showing a significant increase of IL-17A and IL-23 serum levels in patients with gonorrhoea, suggesting new players in the immune response to N. gonorrhoeae.

Trend of ciprofloxacin resistance in Neisseria gonorrhoeae strains isolated in Italy and analysis of the molecular determinants.

A total of 599 Neisseria gonorrhoeae strains collected in Italy in 2 periods, 2003 to 2005 and 2007 to 2008, were screened for ciprofloxacin susceptibility by Etest. Ciprofloxacin-resistant strains (49.7%) were characterized by i) serovar determination, patterns of mutation in gyrA, and parC genes (38%, randomly selected) and ii) N. gonorrhoeae multiantigen sequence typing (56% of the strains isolated from patients who declared their sexual orientation). The percentage of ciprofloxacin-resistant strains increased from 42 (2003-2005) to 58 (2007-2008); in the second period, strains with MIC value >32 microg/mL have been observed. Mutations in gyrA and parC genes were identified in the majority of strains (88%). Ciprofloxacin-resistant isolates among men who have sex with men (MSM) increased from 24% in 2003 to 2005 to 47% in 2007 to 2008. However, sequence types exclusively found among MSM were mostly due to a single strain. This is the first study in Italy combining N. gonorrhoeae ciprofloxacin susceptibility testing with molecular analyses and comparing the results over time.

Molecular analysis of two novel Neisseria gonorrhoeae virulent components: the macrophage infectivity potentiator and the outer membrane protein A.

Molecular analyses of mip and ompA genes were performed on 20 Neisseria gonorrhoeae isolates. The genes were present with a high degree of conservation in all strains. Sera from patients with urethritis or disseminated gonococcal infections were able to recognize the purified Neisseria gonorrhoeae macrophage infectivity potentiator (Ng-MIP) and Neisseria gonorrhoeae outer membrane protein A (Ng-OmpA).

Molecular analysis of tetracycline-resistant gonococci: rapid detection of resistant genotypes using a real-time PCR assay.

The aim of this study was to examine tetracycline-resistant gonococci and to set up a real-time PCR method to identify, in the same assay, both the chromosomally and the plasmid-mediated tetracycline-resistant genotypes. A retrospective analysis for tetracycline susceptibility was performed by the E-test and agar dilution methods on 289 gonococci isolated in Italy from 2003 to 2005. Molecular mechanisms of resistance were investigated by both sequence analyses of the three main genes associated with chromosomally mediated resistance (mtrR, penB and rpsJ genes) and by the identification of plasmids carrying the tetM determinant associated with plasmid-mediated resistance, by PCR (American- or Dutch-type plasmids). The genetic relatedness of nonsusceptible strains was evaluated by pulsed field gel electrophoresis (PFGE). The results showed the presence of 22.5% tetracycline-resistant and 49.5% tetracycline-intermediate gonococci. Coexistence of chromosomally and plasmid-mediated resistance to tetracycline was observed in the majority of resistant isolates. No clonal structure was highlighted by analysis of PFGE pattern profiles. Real-time PCR assay was able to identify all the tetracycline nonsusceptible gonococci correctly for the presence of both chromosomally and/or plasmid-mediated genotypes.

Characterization of invasive serogroup Y meningococci in Italy: prevalence of ST-23 Complex/Cluster A3.

The percentage of Neisseria meningitidis serogroup Y isolated from patients with invasive meningococcal disease (IMD) in Italy has increased from 1998 to 2006. In this study, phenotypic features and genetic relatedness have been investigated in all serogroup Y meningococci isolated during that period. Multilocus sequence typing (MLST) identified the ST-23 complex/Cluster A3 as the major clonal complex in 88.8% of the strains. That complex included all strains belonging to the sequence type (ST) 23 isolated from 1998 to 2004, whereas the ST-3171 was prevalent among strains in the years 2005 and 2006. The STs 23 and 3171 differ for only one nucleotide in the phosphoglucomutase (pgm) housekeeping gene. Over 80% of serogroup Y ST-23 complex/Cluster A3 strains showed phenotype Y:14:NST and 85% of the latter resulted indistinguishable by pulsed-field gel electrophoresis analysis. In 2005, serogroup Y meningococci with decreased susceptibility to penicillin were isolated for the first time in Italy. In the following year, three of the seven strains showed this phenotype. The results of this study allow us to draw a profile of the molecular characteristics of invasive serogroup Y in Italy and will be helpful to monitor the spread of this serogroup in the next years.

Disseminated gonococcal infection in an immunocompetent patient caused by an imported Neisseria gonorrhoeae multidrug-resistant strain.

We herein report the microbiological features of a Neisseria gonorrhoeae strain isolated from an immunocompetent patient with disseminated gonococcal infection (DGI). The strain expressed the IA/IB serovar; was resistant to penicillin, tetracycline, and ciprofloxacin; and had presumably been acquired in Southeast Asia. To date, this is the first case reported in our country of DGI due to an imported multidrug-resistant strain.