scholarly journals Time-kill curve analysis and pharmacodynamic functions for in vitro evaluation of antimicrobials againstNeisseria gonorrhoeae

2015 ◽  
Author(s):  
Sunniva Foerster ◽  
Magnus Unemo ◽  
Lucy J Hathaway ◽  
Nicola Low ◽  
Christian L Althaus

Gonorrhea is a sexually transmitted infection caused by the Gram-negative bacteriumNeisseria gonorrhoeae. Resistance to first-line empirical monotherapy has emerged, so robust methods are needed to appropriately evaluate the activity of existing and novel antimicrobials against the bacterium. Pharmacodynamic functions, which describe the relationship between the concentration of antimicrobials and the bacterial net growth rate, provide more detailed information than the MIC only. In this study, a novel standardized in vitro time-kill curve assay was developed. The assay was validated using five World Health OrganizationN. gonorrhoeaereference strains and various concentrations of ciprofloxacin, and then the activity of nine antimicrobials with different target mechanisms were examined against a highly susceptible clinical wild type isolate (cultured in 1964). From the time-kill curves, the bacterial net growth rates at each antimicrobial concentration were estimated. Finally, a pharmacodynamic function was fitted to the data, resulting in four parameters that describe the pharmacodynamic properties of each antimicrobial. Ciprofloxacin resistance determinants shifted the pharmacodynamic MIC (zMIC) and attenuated the bactericidal effect at antimicrobial concentrations above the zMIC. Ciprofloxacin, spectinomycin and gentamicin had the strongest bactericidal effect during the first six hours of the assay. Only tetracycline and chloramphenicol showed a purely bacteriostatic effect. The pharmacodynamic functions differed between antimicrobials, showing that the effect of the drugs at concentrations below and above the MIC vary widely. In conclusion,N. gonorrhoeaetime-kill curve experiments analyzed with pharmacodynamic functions have potential for in vitro evaluation of new and existing antimicrobials and dosing strategies to treat gonorrhea.

2019 ◽  
Vol 74 (12) ◽  
pp. 3521-3529 ◽  
Author(s):  
Sunniva Foerster ◽  
George Drusano ◽  
Daniel Golparian ◽  
Michael Neely ◽  
Laura J V Piddock ◽  
...  

Abstract Objectives Resistance in Neisseria gonorrhoeae to all gonorrhoea therapeutic antimicrobials has emerged. Novel therapeutic antimicrobials are imperative and the first-in-class spiropyrimidinetrione zoliflodacin appears promising. Zoliflodacin could be introduced in dual antimicrobial therapies to prevent the emergence and/or spread of resistance. We investigated the in vitro activity of and selection of resistance to zoliflodacin alone and in combination with six gonorrhoea therapeutic antimicrobials against N. gonorrhoeae. Methods The international gonococcal reference strains WHO F (WT) and WHO O, WHO V and WHO X (strains with different AMR profiles) were examined. Zoliflodacin was evaluated alone or combined with ceftriaxone, cefixime, spectinomycin, gentamicin, tetracycline, cethromycin or sitafloxacin in chequerboard assays, time–kill curve analysis and selection-of-resistance studies. Results Zoliflodacin alone or in combination with all six antimicrobials showed rapid growth inhibition against all examined strains. The time–kill curve analysis indicated that tetracycline or cethromycin combined with zoliflodacin can significantly decrease the zoliflodacin kill rate in vitro. The frequency of selected zoliflodacin-resistance mutations was low when evaluated as a single agent and further reduced for all antimicrobial combinations. All resistant mutants contained the GyrB mutations D429N, K450T or K450N, resulting in zoliflodacin MICs of 0.5–4 mg/L. Conclusions Zoliflodacin, alone or in combination with sexually transmitted infection therapeutic antimicrobials, rapidly kills gonococci with infrequent resistance emergence. Zoliflodacin remains promising for gonorrhoea oral monotherapy and as part of dual antimicrobial therapy with low resistance emergence potential. A Phase III trial evaluating efficacy and safety of zoliflodacin for uncomplicated gonorrhoea treatment is planned in 2019.


2005 ◽  
Vol 10 (37) ◽  
Author(s):  
M Lehtinen

At a World Health Organization meeting, the latest developments in human papillomavirus (HPV) vaccination were discussed. The leading theme that emerged was how to implement within national programmes the concept of vaccinating adolescents both against a common sexually transmitted infection


2021 ◽  
Vol 3 ◽  
Author(s):  
Karina Nava-Memije ◽  
Cecilia Hernández-Cortez ◽  
Verónica Ruiz-González ◽  
Claudia A. Saldaña-Juárez ◽  
Yazmín Medina-Islas ◽  
...  

The World Health Organization (WHO) and the Joint United Nations Programme on HIV and AIDS (UNAIDS) suggest that sexually transmitted infection (STI) surveillance should include other genital infections and not only human immunodeficiency virus (HIV). To monitor the concomitance of bacterial vaginosis (BV) and STIs in HIV-seropositive (HIV+) and HIV-seronegative (HIV–) patients, a prospective study was conducted in a cohort of 349 volunteers at a clinic specializing in treating STIs in Mexico City. Microbiological and molecular methods were used to detect STIs and dysbiosis in HIV+ and HIV– individuals. The prevalence of infection was higher in HIV+ (69.28%) than in HIV– (54.87%) individuals. BV was the most frequent infection in HIV+ individuals, and polymicrobial infections were 3 times more common in HIV+ individuals than in HIV– individuals (31.48 vs. 10.98%). Behaviors documented in a self-administered questionnaire included low condom use frequency in HIV+ individuals co-infected with BV or a STI. This finding highlights the importance of surveillance using routine microbiological evaluations for the correct management of genital infections in HIV+ patients because in the presence of HIV, the clinical presentations, courses, and therapeutic responses of some STIs can differ from those in patients without HIV infection.


2021 ◽  
Vol 8 (1) ◽  
pp. 160-165
Author(s):  
Masaaki Minami ◽  
Takafumi Ando ◽  
Hidemi Goto ◽  
Michio Ohta

Mupirocin (MUP) is an effective antibiotic against MRSA. Its bactericidal effect is stable under acid condition. By validating its antibacterial effect of Helicobacter pylori, we try to clarify MUP effect on H. pylori. The present study was conducted to investigate the effect of MUP on clarithromycin (CLR) / metronidazole (MNZ) -resistant and -susceptible strains of H. pylori, the time-kill effect of MUP, and the post antibiotic effect (PAE). We investigated the minimal inhibitory concentration (MIC) and the minimal bactericidal effect (MBC) of MUP against 140 H. pylori, which include clinical strains, ATCC43504, 26695 and J99. Ten of them were CLR -resistant strains and 3 were MNZ-resistant strains. The MIC90 and MBC of MUP on all 140 strains is 0.064 μg / ml, and 0.1 μg / ml, respectively. There were no differences of MUP effect between susceptible and resistant strains either for CLR or MNZ. Time-kill curve test and PAE test of MUP on ATCC43504 were performed. By adding MUP, time-kill curve showed that bacterial quantities decreased in dose and time-dependent manner. No viable colony was found after 12-hour culture with 0.1 μg / ml MUP. The value of PAE is 12. MUP is a potential effective antibiotic for H. pylori even those for CLR / MNZ -resistant strains.


2008 ◽  
Vol 52 (5) ◽  
pp. 1697-1702 ◽  
Author(s):  
S. Grayo ◽  
O. Join-Lambert ◽  
M. C. Desroches ◽  
A. Le Monnier

ABSTRACT Listeria monocytogenes is a facultative intracellular bacterium that causes severe infections associated with a high mortality rate. Moxifloxacin presents extended activity against gram-positive bacteria and has recently been suggested to be a potential alternative in the treatment of listeriosis. We evaluated the in vitro efficacy of moxifloxacin against L. monocytogenes using a combination of epidemiological and experimental approaches. The median MIC of moxifloxacin for a large collection of L. monocytogenes strains of various origins (human, food, and environment) was 0.5 μg/ml (MIC range, 0.064 to 1 μg/ml). No differences were observed, irrespective of the origin of the strains. Moreover, no cross-resistance with fluoroquinolones was detected in strains that have been reported to be resistant to ciprofloxacin. The in vitro activities of moxifloxacin and amoxicillin were compared by time-kill curve and inhibition of intracellular growth experiments by using a model of bone marrow-derived mouse macrophages infected by L. monocytogenes EGDe. Both moxifloxacin and amoxicillin were bactericidal in broth against extracellular forms of L. monocytogenes. However, moxifloxacin acted much more rapidly, beginning to exert its effects in the first 3 h and achieving complete broth sterilization within 24 h of incubation. Moxifloxacin has a rapid bactericidal effect against intracellular reservoirs of bacteria, whereas amoxicillin is only bacteriostatic and appears to prevent cellular lysis and the subsequent bacterial spreading to adjacent cells. No resistant bacteria were selected during the in vitro experiments. Taken together, our results suggest that moxifloxacin is an interesting alternative to the reference treatment, combining rapid and bactericidal activity, even against intracellular bacteria.


2019 ◽  
Author(s):  
Daiva Odelia

Sexually transmitted infection (STIs) is infections that transmitted from one individual to another commonly by sexual activities. STIs can also be referred as STDs (Sexual transmitted diseases). In present-day, STIs cause of mortality around the world especially in developed country. There are more than 30 different agents that can be transmitted and cause STIs. One of the most famous STIs that cause by bacteria, is gonorrhea. Gonorrhea is caused by infection of Neisseria gonorrhea by sexual activity and is currently become one of three primary focus infections that require immediate action according to World Health Organization. It can be occured in both men and women even though there is different rate of visibility in the two sexes. In women, gonorrhea often happens to be asymptomatic. Teenager is the group of people who is most susceptible in the spread of STI.


mBio ◽  
2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Mohsen Chitsaz ◽  
Vrinda Gupta ◽  
Benjamin Harris ◽  
Megan L. O’Mara ◽  
Melissa H. Brown

The historical sexually transmitted infection gonorrhea continues to be a major public health concern with an estimated global annual incidence of 86.9 million cases. N. gonorrhoeae has been identified by the World Health Organization as one of the 12 antimicrobial-resistant bacterial species that poses the greatest risk to human health. As the major efflux pump in gonococci, the MtrD transporter contributes to the cell envelope barrier in this organism and pumps antimicrobials from the periplasm and inner membrane, resulting in resistance.


Author(s):  
María Ángeles Pérez-Morente ◽  
María Gázquez-López ◽  
María Adelaida Álvarez-Serrano ◽  
Encarnación Martínez-García ◽  
Pedro Femia-Marzo ◽  
...  

The World Health Organization estimates that more than one million people acquire a Sexually Transmitted Infection (STI) every day, compromising quality of life, sexual and reproductive health, and the health of newborns and children. It is an objective of this study to identify the factors related to a Sexually Transmitted Infection diagnosis in the province of Granada (Spain), as well as those better predicting the risk of acquiring such infections. In this study, 678 cases were analyzed on a retrospective basis, which were treated at the Centre for Sexually Transmitted Diseases and Sexual Orientation in Granada, between 2000–2014. Descriptive statistics were applied, and by means of binary logistic regression, employing the forward stepwise-likelihood ratio, a predictive model was estimated for the risk of acquiring an STI. Sex, age, occupation, economic crisis period, drug use, number of days in which no condoms were used, number of sexual partners in the last month and in the last year, and number of subsequent visits and new subsequent episodes were associated with an STI diagnosis (p < 0.05). The risk of being diagnosed with an STI increased during the economic crisis period (OR: 1.88; 95%-CI: 1.28–2.76); during the economic crisis and if they were women (OR:2.35, 95%- CI: 1.24–4.44); and if they were women and immigrants (OR: 2.09; 95%- CI:1.22–3.57), while it decreased with age (OR: 0.97, 95%-CI: 0.95–0.98). Identification of the group comprised of immigrant women as an especially vulnerable group regarding the acquisition of an STI in our province reflects the need to incorporate the gender perspective into preventive strategies and STI primary health care.


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