Factors associated with rectal pH among men who have sex with men
Fabian Y. S. Kong
A D , Jacqueline Woutersen B , Michelle M. Kroone B , Jane S. Hocking A * and Henry J. C. de Vries C *
A Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, 3/207 Bouverie St, Melbourne, Vic. 3004, Australia.
B Public Health Service of Amsterdam (GGD Amsterdam), PO Box 2200, 1000 CE Amsterdam, The Netherlands.
C Amsterdam UMC, University of Amsterdam, Department of Dermatology, Amsterdam Institute for Infection and Immunity, Academic Medical Centre & STI Outpatient Clinic, Department of Infectious Diseases, Public Health Service Amsterdam, The Netherlands.
D Corresponding author. Email: kongf@unimelb.edu.au
Sexual Health 18(2) 140-146 https://doi.org/10.1071/SH20107
Submitted: 17 June 2020 Accepted: 11 December 2020 Published: 9 March 2021
Abstract
Background: Rectal chlamydia treatment failures up to 22% with azithromycin 1 g have been reported, but low tissue concentrations are unlikely to be the cause. Anecdotally, low rectal pH could reduce rectal azithromycin concentrations, with in vitro studies reporting higher minimum inhibitory concentrations (MICs) with lower pHs for antibiotics used to treat sexually transmissible infections (STIs). Leucocytes arising from an inflammatory immune response could also lower pH and efficacy. We examined factors that may alter rectal pH and potentially influence treatment outcomes. Methods: We recruited consecutive men who have sex with men (MSM) from a Dutch STI clinic between October 2016 and July 2018 who had not used antibiotics in the past fortnight. Rectal mucus collected under anoscopy using a cotton swab was used to wet a pH indicator strip. Logistic regression was used to examine the association of pH <8.0 to demographic, dietary, sexual health and behaviour data, recent medication use and STI diagnosis. Results: In total, 112 MSM were recruited (median age 37 years). It was found that 45% and 39% of men were HIV positive or had a rectal infection, respectively. And 50% had a rectal pH <8.0, with 27% reporting a pH between 6.0 and 6.5 where treatment failure is thought to occur for azithromycin. The adjusted odds ratio (OR) of a pH <8.0 showed that being aged 36–45 years (OR 6.7; 95%CI: 1.9–23.4) or having high rectal leucocytes in a Gram smear (OR 0.3; 95%CI: 0.1–0.7) were significantly associated with a low and high rectal pH, respectively. Conclusions: Lower rectal pH among MSM is associated with older age and could influence the rectal pharmacokinetics of azithromycin and other drugs influenced by pH and may therefore affect treatment outcomes.
Keywords: anorectal, azithromycin, Chlamydia trachomatis, pH, pharmacokinetics, risk behaviour, treatment effectiveness.
References
[1] Newman L, Rowley J, Vander Hoorn S, et al Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS One 2015; 10 e0143304| Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting.Crossref | GoogleScholarGoogle Scholar | 26646541PubMed |
[2] Chan PA, Robinette A, Montgomery M, et al Extragenital infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae: a review of the literature. Infect Dis Obstet Gynecol 2016; 2016 5758387
| Extragenital infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae: a review of the literature.Crossref | GoogleScholarGoogle Scholar | 27366021PubMed |
[3] Ward H, Ronn M. Contribution of sexually transmitted infections to the sexual transmission of HIV. Curr Opin HIV AIDS 2010; 5 305–10.
| Contribution of sexually transmitted infections to the sexual transmission of HIV.Crossref | GoogleScholarGoogle Scholar | 20543605PubMed |
[4] Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64 1–137.
| 26042815PubMed |
[5] Kong FYS, Tabrizi SN, Fairley CK, et al The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis. J Antimicrob Chemother 2015; 70 1290–7.
| The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis.Crossref | GoogleScholarGoogle Scholar |
[6] Wang SA, Papp JR, Stamm WE, et al Evaluation of antimicrobial resistance and treatment failures for Chlamydia trachomatis: a meeting report. J Infect Dis 2005; 191 917–23.
| Evaluation of antimicrobial resistance and treatment failures for Chlamydia trachomatis: a meeting report.Crossref | GoogleScholarGoogle Scholar | 15717267PubMed |
[7] Kong FYS, Rupasinghe TW, Simpson JA, et al Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men. PLoS One 2017; 12 e0174372
| Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men.Crossref | GoogleScholarGoogle Scholar | 28498845PubMed |
[8] Bitterman W, Spencer R, Huizenga K, et al Contact pH of rectal mucosa in humans and dogs. Dis Colon Rectum 1969; 12 96–8.
| Contact pH of rectal mucosa in humans and dogs.Crossref | GoogleScholarGoogle Scholar | 5774854PubMed |
[9] Wildfeuer A, Laufen H, Müller-Wening D, et al Interaction of azithromycin and human phagocytic cells. Uptake of the antibiotic and the effect on the survival of ingested bacteria in phagocytes. Arzneimittelforschung 1989; 39 755–8.
| 2551303PubMed |
[10] Pfizer Canada. Zithromax product information. Pfizer Canada; 2013.
[11] Meanwell NA. Tactics in contemporary drug design. USA: Springer; 2015.
[12] Babić S, Horvat AJM, Mutavdžić Pavlović D, et al Determination of pKa values of active pharmaceutical ingredients. Trends Analyt Chem 2007; 26 1043–61.
| Determination of pKa values of active pharmaceutical ingredients.Crossref | GoogleScholarGoogle Scholar |
[13] Carbon C. Pharmacodynamics of macrolides, azalides, and streptogramins: effect on extracellular pathogens. Clin Infect Dis 1998; 27 28–32.
| Pharmacodynamics of macrolides, azalides, and streptogramins: effect on extracellular pathogens.Crossref | GoogleScholarGoogle Scholar | 9675445PubMed |
[14] Foschi C, Salvo M, Cevenini R, et al Chlamydia trachomatis antimicrobial susceptibility in colorectal and endocervical cells. J Antimicrob Chemother 2018; 73 409–13.
| Chlamydia trachomatis antimicrobial susceptibility in colorectal and endocervical cells.Crossref | GoogleScholarGoogle Scholar | 29077843PubMed |
[15] Barcia-Macay M, Seral C, Mingeot-Leclercq MP, et al Pharmacodynamic evaluation of the intracellular activities of antibiotics against Staphylococcus aureus in a model of THP-1 macrophages. Antimicrob Agents Chemother 2006; 50 841–51.
| Pharmacodynamic evaluation of the intracellular activities of antibiotics against Staphylococcus aureus in a model of THP-1 macrophages.Crossref | GoogleScholarGoogle Scholar | 16495241PubMed |
[16] Hinkle AM, Bodey GP. In vitro evaluation of Ro 13–9904. Antimicrob Agents Chemother 1980; 18 574–8.
| In vitro evaluation of Ro 13–9904.Crossref | GoogleScholarGoogle Scholar | 6778383PubMed |
[17] Debbia EA, Marchese A, Pesce A, et al Parameters characterizing the in vitro activity of cefixime, a new oral broad spectrum cephalosporin, against respiratory and urinary pathogens. J Chemother 1992; 4 131–44.
| Parameters characterizing the in vitro activity of cefixime, a new oral broad spectrum cephalosporin, against respiratory and urinary pathogens.Crossref | GoogleScholarGoogle Scholar | 1517806PubMed |
[18] Fuchs EJ, Lee LA, Torbenson MS, et al Hyperosmolar sexual lubricant causes epithelial damage in the distal colon: potential implication for HIV transmission. J Infect Dis 2007; 195 703–10.
| Hyperosmolar sexual lubricant causes epithelial damage in the distal colon: potential implication for HIV transmission.Crossref | GoogleScholarGoogle Scholar | 17262713PubMed |
[19] Beharka AA, Paiva S, Leka LS, et al Effect of age on the gastrointestinal-associated mucosal immune response of humans J Gerontol A Biol Sci Med Sci 2001; 56 B218–B223.
| Effect of age on the gastrointestinal-associated mucosal immune response of humansCrossref | GoogleScholarGoogle Scholar | 11320102PubMed |
[20] Saraswati S, Sitaraman R. Aging and the human gut microbiota-from correlation to causality. Front Microbiol 2015; 5 764
| 25628610PubMed |
[21] Schmelzer M, Schiller LR, Meyer R, et al Safety and effectiveness of large-volume enema solutions. Appl Nurs Res 2004; 17 265–74.
| 15573335PubMed |
[22] De Milito A, Canese R, Marino ML, et al pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity. Int J Cancer 2010; 127 207–19.
| pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity.Crossref | GoogleScholarGoogle Scholar | 19876915PubMed |
[23] Imhann F, Bonder MJ, Vich Vila A, et al Proton pump inhibitors affect the gut microbiome. Gut 2016; 65 740–8.
| Proton pump inhibitors affect the gut microbiome.Crossref | GoogleScholarGoogle Scholar | 26657899PubMed |
[24] Zimmer J, Lange B, Frick JS, et al A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur J Clin Nutr 2012; 66 53–60.
| A vegan or vegetarian diet substantially alters the human colonic faecal microbiota.Crossref | GoogleScholarGoogle Scholar | 21811294PubMed |
[25] Donders G. Diagnosis and management of bacterial vaginosis and other types of abnormal vaginal bacterial Flora: a review. Obstet Gynecol Surv 2010; 65 462–73.
| Diagnosis and management of bacterial vaginosis and other types of abnormal vaginal bacterial Flora: a review.Crossref | GoogleScholarGoogle Scholar | 20723268PubMed |
[26] Eggert-Kruse W, Köhler A, Rohr G, Runnebaum B. The pH as an important determinant of sperm-mucus interaction. Fertil Steril 1993; 59 617–28.
| The pH as an important determinant of sperm-mucus interaction.Crossref | GoogleScholarGoogle Scholar | 8458467PubMed |
[27] Aframian DJ, Davidowitz T, Benoliel R. The distribution of oral mucosal pH values in healthy saliva secretors. Oral Dis 2006; 12 420–3.
| The distribution of oral mucosal pH values in healthy saliva secretors.Crossref | GoogleScholarGoogle Scholar | 16792729PubMed |
