Position statement of the German STI Society on the prophylactic use of doxycycline to prevent STIs (Doxy-PEP, Doxy-PrEP).

Over the past two decades, there has been a rise in the incidence of syphilis, particularly among men who have sex with men (MSM). This has sparked interest in studying the prophylactic use of doxycycline to prevent syphilis and other sexually transmitted infections (STIs), commonly referred to as Doxycycline Pre- or Post-Exposure Prophylaxis (Doxy-PrEP, Doxy-PEP). At the same time, demand from potential users for this preventive measure is increasing. Several randomized controlled trials have demonstrated that the prophylactic use of doxycycline in MSM and trans women using HIV pre-exposure prophylaxis (HIV-PrEP) or living with an HIV infection effectively reduces the risk of syphilis and chlamydia infections. At present, however, unresolved questions remain, particularly regarding implications of a broad implementation of prophylactic doxycycline to prevent STIs on tetracycline and other antimicrobial resistance in bacterial STIs, non-STI-related bacterial pathogens, and the microbiome. In response to the increasing demand and the challenge of balancing effectiveness, safety, and the risk of promoting antibiotic resistance, the German STI Society (DSTIG) has issued a position statement, providing specific recommendations regarding potential indications, criteria, and occasions for the use of doxycycline in STI prevention. These recommendations are based on current evidence and expert opinion.

Prevalence and antibiotic resistance of rectal Mollicutes in HIV-infected men who have sex with men at the University Hospital of Dresden, Germany.

BACKGROUND: Rectal sexually transmitted infections (STI) are common in men having sex with men (MSM). Mycoplasma genitalium is increasingly being reported in this localization, but due to frequent lack of symptoms at this site, clinical significance is still unclear. Rectal prevalence of Mycoplasma hominis and Ureaplasma species is not well studied so far. We aimed to investigate the prevalence and antibiotic sensitivity of rectal Mollicutes in our HIV-cohort. METHODS: In 227 MSM presenting for annual STI-screening, 317 anorectal swabs were collected from January 2017 to December 2018. PCR was performed for detection of Chlamydia trachomatis, Neisseria gonorrhoeae, M. genitalium and also culture for M. hominis and Ureaplasma spec. RESULTS: Prevalence for M. genitalium, M. hominis, Ureaplasma spec., C. trachomatis and N. gonorrhoeae was 8.2%, 7.3%, 12.0%, 5.1% and 1.9%, respectively. Patients were asymptomatic with few exceptions. Seroprevalence of syphilis in 227 MSM was 41.9%. In 20 strains of M. genitalium, resistance-associated mutations to macrolides and quinolones were found in 60% and 30%, respectively; in five strains (25%) to both. M. hominis and Ureaplasma spec. frequently occurred combined, mostly in significant quantity consistent with infection. M. hominis and Ureaplasma spec. regularly showed sensitivity to tetracycline. CONCLUSION: At screening, rectal colonization with Mollicutes was common in our patients, but rarely caused symptoms. Due to rising antibiotic resistance of M. genitalium against quinolones, therapeutic options are increasingly limited. Treatment should be guided by antibiotic resistance testing including quinolones. In persisting anorectal symptoms, M. hominis and Ureaplasma spec. should also be taken into account.

STI in times of PrEP: high prevalence of chlamydia, gonorrhea, and mycoplasma at different anatomic sites in men who have sex with men in Germany.

BACKGROUND: Men who have sex with men (MSM) are disproportionally affected by sexually transmitted infections (STI). STI are often extragenital and asymptomatic. Both can delay diagnosis and treatment. Approval of HIV pre-exposure prophylaxis (PrEP) might have influenced sexual behaviour and STI-prevalence of HIV- MSM. We estimated STI-prevalence and risk factors amongst HIV- and HIV+ MSM in Germany to plan effective interventions. METHODS: We conducted a nationwide, cross-sectional study between February and July 2018. Thirteen MSM-friendly STI-practices screened MSM for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhea (NG), and Trichomonas vaginalis (TV) using self-collected rectal and pharyngeal swabs, and urine samples. APTIMA™ STI-assays (Hologic™ Inc., San Diego, USA) were used for diagnostics, and samples were not pooled. We collected information on socio-demographics, HIV-status, clinical symptoms, sexual behaviour within the last 6 months, and PrEP use. We combined HIV status and PrEP use for defining risk groups, and used directed acyclic graphs and multivariable logistic regression to identify risk factors for STI. RESULTS: Two thousand three hundred three MSM were included: 50.5% HIV+, median age 39 [18-79] years. Median number of male sex partners within the last 6 months was five. Sex without condom was reported by 73.6%, use of party drugs by 44.6%. 80.3% had a STI history, 32.2% of STI+ MSM reported STI-related symptoms. 27.6% of HIV- MSM used PrEP. Overall STI-prevalence was 30.1, 25.0% in HIV-/PrEP- MSM (CT:7.2%; MG:14.2%; NG:7.4%; TV:0%), 40.3% in HIV-/PrEP+ MSM (CT:13.8%; MG:19.4%; NG:14.8%; TV:0.4%), and 30.8% in HIV+ MSM (CT:10.1%; MG:18.4%; NG:8.6%; TV:0.1%). Being HIV+ (OR 1.7, 95%-CI 1.3-2.2), using PrEP (OR 2.0, 95%-CI 1.5-2.7), having > 5 sex partners (OR:1.65; 95%-CI:1.32-2.01.9), having condomless sex (OR:2.11.9; 95%-CI:1.65-2.86), and using party drugs (OR:1.65; 95%-CI:1.32-2.0) were independent risk factors for being tested positive for at least one STI. CONCLUSIONS: We found a high STI-prevalence in MSM in Germany, especially in PrEP users, frequently being asymptomatic. As a relevant proportion of PrEP users will not use a condom, counselling and comprehensive STI screening is essential and should be low threshold and preferably free of cost. Counselling of PrEP users should also address use of party drugs.

Occupational allergy to phytase: case series of eight production workers exposed to animal feed additives.

BACKGROUND: In agricultural meat production, adding enzymes such as phytase to animal feed is widespread, but there is little awareness of the allergenic potential and health risks of these fungal enzymes. PATIENTS AND METHODS: We report on eight patients working in a plant producing phytase granulates. All patients complained about work-related rhinitis occurring within six months of the onset of exposure to phytase dust. Asthmatic symptoms and contact urticaria also occurred. To detect sensitizations to phytase, skin prick-, patch-, and basophil activation test were carried out with the factory product. Levels of IgE and IgG against phytase were also measured. RESULTS: There was a positive reaction to phytase with skin prick testing in seven of the eight patients. IgE specific to phytase was detectable in four of the eight patients, and IgG specific to phytase was detectable in six of the eight patients. The basophil activation test was positive in four out of seven patients tested, but the patch test was negative in all patients tested. Transfer to a different workplace with no exposure to phytase completely eliminated the symptoms. CONCLUSIONS: Mold enzymes such as phytase are highly potent occupational allergens. Occupational safety measures must be strictly implemented in order to protect the health of workers.

S3 guidelines: Epicutaneous patch testing with contact allergens and drugs - Short version, Part 1.

Epicutaneous patch testing is the diagnostic standard for the detection of allergic contact dermatitis. The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology and allergology as well as other medical specialties involved in establishing the indication for patch testing and its execution in patients with contact dermatitis and other forms of delayed-type hypersensitivity. The target audience also includes other health care providers and insurance funds. Based on a systematic literature search and a formal consensus process (S3), the guidelines were developed by dermatologists in collaboration with pediatricians, occupational medicine physicians, nursing staff as well as patient representatives. The systematic methodological approach and appraisal of evidence upon which the recommendations are based are outlined in a separate method report that also contains evidence tables. The guidelines address general aspects of patch testing as well as medicolegal issues. The recommendations given relate to topics such as the indication for patch testing, informed patient consent, as well as the choice of test substances, test chambers and test site, duration of exposure, reading times and interpretation of test reactions. Furthermore, recommendations are provided with respect to endogenous and exogenous factors, specific patient groups (children, pregnant women, immunosuppressed individuals) as well as possible risks and adverse events associated with patch testing using contact allergens. Note: This publication is part 1 of the short version of the S3 guidelines for "Epicutaneous patch testing using contact allergens and drugs" (registry no. 013 - 018; date: March 20, 2019; valid until December 31, 2021). Part 2 of the short version will be published in the next issue. The long version of these guidelines can be accessed at www.awmf.org. The method report is available as online publication (https://www.awmf.org/leitlinien/detail/ll/013-018.html) and contains the evidence tables in its appendix.

S3 Guidelines: Epicutaneous patch testing with contact allergens and drugs - Short version, Part 2.

Epicutaneous patch testing is the diagnostic standard for the detection of allergic contact dermatitis. The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology and allergology as well as other medical specialties involved in establishing the indication for patch testing and its execution in patients with contact dermatitis and other forms of delayed-type hypersensitivity. The target audience also includes other health care providers and insurance funds. Based on a systematic literature search and a formal consensus process (S3), the guidelines were developed by dermatologists in collaboration with pediatricians, occupational medicine physicians, nursing staff as well as patient representatives. The systematic methodological approach and appraisal of evidence upon which the recommendations are based are outlined in a separate method report that also contains evidence tables. The guidelines address general aspects of patch testing as well as medicolegal issues. The recommendations given relate to topics such as the indication for patch testing, informed patient consent, as well as the choice of test substances, test chambers and test site, duration of exposure, reading times and interpretation of test reactions. Furthermore, recommendations are provided with respect to endogenous and exogenous factors, specific patient groups (children, pregnant women, immunosuppressed individuals) as well as possible risks and adverse events associated with patch testing using contact allergens.

Safety and tolerability during build-up phase of a rush venom immunotherapy.

BACKGROUND: Safety and tolerability of venom immunotherapy (VIT) in patients with concomitant disease and comedications, especially ß-blockers (BBs) and angiotensin-converting enzyme inhibitors (ACEIs), are under discussion. OBJECTIVE: To identify risk factors for the occurrence of systemic reactions (SRs) during the build-up phase of a 3-day rush VIT with focus on comorbidities and related comedications. METHODS: Data of 175 three-day rush VIT courses (Vespula venom, n = 161; honeybee venom, n = 14) were analyzed. Starting with 0.02 µg of venom, the maintenance dose of 100 µg was reached in 15-dose increments within 3 days. Local reactions (LRs) and SRs were documented during the build-up phase. Comorbidities and related comedications were registered. Univariate, bivariate, and multivariate data analysis was performed. RESULTS: During the 3-day rush VIT, an LR was seen in 74 (42.3%) of 175, a large LR (>10-cm diameter) in 82 (46.9%) of 175, and SRs in 19 (10.9%) of 175 VIT courses. Multivariate logistic regression revealed that female sex (P = .01), immunotherapy with honeybee venom (P = .003), and accompanying ACEI medication (P = .03) were independent predictors of the development of SRs during the build-up phase of VIT. CONCLUSION: This study revealed that female sex, honeybee VIT, and ACEI use independent predictors for SRs.

Characteristics and coinfection with syphilis in newly HIV-infected patients at the University Hospital Dresden 1987-2012.

BACKGROUND: In Germany, notification data cannot be used to determine HIV and syphilis coinfection. No regional cohort has been studied for this in Eastern Germany. The rising incidence of syphilis from 2010 to 2012, predominantly in men having sex with men (MSM), has been suggested as a cause for recent increases in HIV infection rates in this group. PATIENTS AND METHODS: Characteristics of 355 consecutive patients newly diagnosed with HIV infection at the University Hospital Dresden 1987-2012 were retrospectively compared to German surveillance data from the region of Dresden. Additionally, coinfection with syphilis was determined. RESULTS: Compared to German surveillance data, we observed higher proportions of persons originating from high prevalence countries and of AIDS cases. In the age group of up to 25 years, the proportion of MSM has risen 3-fold since 2001. At time of HIV diagnosis, seroprevalence of syphilis was 20.3 %. Active syphilis (VDRL ≥ 1: 8) occurred in 6.7 % of patients, predominantly MSM, who also exhibited a significantly higher HIV viral load. CONCLUSIONS: Our findings suggest a causative relationship between recently rising incidences of syphilis and HIV infection in MSM. Early diagnosis of syphilis may promote earlier diagnosis of HIV infection; therefore, HIV prevention measures should also include other sexually transmitted infections.

Decreased perception of bourgeonal may be linked to male idiopathic infertility.

Regarding the chemotaxis of sperms, new insights have been gained during the last 20 years. Olfactory receptors are expressed on the flagellar midpiece of human spermatogenic cells. One of them, OR1D2, is also expressed in the olfactory epithelium. This receptor has been suggested to play a role in sperm chemotaxis and thus in fertility. As OR1D2 is activated by bourgeonal, the aim of the study was to investigate whether patients with idiopathic infertility would exhibit a decreased olfactory sensitivity toward bourgeonal. Participants were 14 patients with idiopathic infertility and 23 controls (all young fathers). After having ascertained normosmia, odor thresholds and intensity ratings for the pleasant and flowery odors of bourgeonal, helional, and phenylethylalcohol were obtained. As a result, patients had specifically decreased intensity ratings for bourgeonal. It suggests that men with unexplained infertility tend to be less suprathreshold sensitive toward the odor of bourgeonal but not to that of other floral odors. It may be speculated that the decreased olfactory sensitivity relates to a decreased functionality of OR1D2, which in turn may be linked to idiopathic infertility.

Metal hypersensitivity and metal ion levels in patients with coated or uncoated total knee arthroplasty: a randomised controlled study.

PURPOSE: Metal ion release by orthopaedic implants may cause local and systemic effects and induce hypersensitivity reactions. Coated implants have been developed to prevent or reduce these effects. This study was initiated to investigate the safety of a novel coating for total knee arthroplasty (TKA) implants. METHODS: A total of 120 patients undergoing primary TKA with no history of hypersensitivity and no other metal implant were randomised to receive either a coated or uncoated implant. Chromium (Cr), cobalt (Co), molybdenum (Mb) and nickel (Ni) hypersensitivity patch testing and plasma ion concentrations were evaluated pre-operatively and one year post-operatively. RESULTS: At the one year follow-up both groups demonstrated significant improvement in knee function and quality of life. One new weakly positive reaction to Co in the TKA group with coated implant and two doubtful skin reactions to Ni (one in each group) were noted. Even with sensitisation to implant materials no skin reactions were observed. Plasma metal ion concentrations did not increase and were not elevated at the one year follow-up in either group. CONCLUSIONS: Sensitisation after TKA was rare and had no influence on clinical results. TKA with coated implant and standard TKA demonstrated no plasma metal ion elevation.

Gonorrhea: Data on antibiotic resistance and accompanying infections at the University Hospital Dresden over a 10-year time period.

BACKGROUND: Over the last years, growing resistance of gonorrhea to quinolones has emerged worldwide. Currently, cases with resistance to oral and parenteral third-generation cephalosporins are increasingly reported. Because gonorrhea is not a notifiable infection in Germany, data on epidemiology and antimicrobial surveillance of gonorrhea are scarce. We present the results of N. gonorrhoea testing at the University Hospital Dresden over the course of ten years. PATIENTS AND METHODS: The results of cultural and nucleic acid amplification testing of gonorrhea and accompanying infections of 1,850 smears between 2001 and 2010 were analyzed retrospectively. RESULTS: Among 181 patients (mean age 30.4 years) 159 had positive PCR analyses for gonorrhea and 50 positive cultures of Neisseria gonorrhoea. The rate of ciprofloxacin resistance was high (in 46% of all isolates), primarily in men. Resistance to cefotaxime and ceftriaxone could not be detected so far. In 40% of the cases at least one accompanying urogenital infection occurred, predominantly with Chlamydia trachomatis. CONCLUSIONS: Similar to other regions of Germany, a high percentage of resistance to quinolones was found in gonorrhea, but not to cephalosporins. Additionally, accompanying infections were frequent and warrant screening. In the light of recent cases of resistance to cephalosporins currently emerging in Europe, cultural diagnosis of gonorrhea should definitely be intensified by all means. The results should be integrated into a surveillance system.