Author response to comment on: a case of intercurrent shigellosis and rectal gonorrhea in an acutely unwell febrile returned traveler

Dear Editor,

We would like to thank Professor Taylor and colleagues for summarizing their very important body of work regarding sexually transmitted shigellosis in the men who have sex with men (MSM) population in response to our published case of intercurrent gonorrhea and Shigella flexneri infection in a febrile returned traveler. ¹ Indeed, we concur that the magnitude of sexual transmission networks globally should be considered in bedside decision-making, and we further concur that guidance for clinical management of sexually transmitted shigellosis is limited. As stated in our paper, “Sexually related gastrointestinal infections, including proctocolitis, have high rates of polymicrobial infection of up to 45.2%. ² These polymicrobial infections consist of enteric pathogens, parasites and classic sexually transmitted infections (STIs). Up to 40% of cases of shigellosis in MSM individuals have been identified to have concomitant STIs, including rectal gonorrhea.” ³ More broadly, we state that “clinical guidelines specific to a patient’s underlying comorbidities and presentation exist, particularly for those living with HIV.” ¹ It is also worth noting that edits made in response to peer review deemphasized our initial stated recommendation that the “current infection control guidelines surrounding shigellosis may need to be examined, particularly in the MSM population.”

Regarding the route of transmission, given that the onset of symptoms occurred on the fifth day of travel following “consumption of raw seafood, local cuisine, unpasteurized dairy” and drinking “local water,” ¹ we cannot exclude potential food-borne transmission. With a typical incubation period for shigellosis of 1–4 days, food-borne transmission in our reported case is probable. However, we certainly agree that with symptom onset 7 days following a sexual encounter, transmission via sexual means is also plausible. As stated, “Our patient had a recent history of condomless intercourse with multiple new partners, increasing risk of transmission for both shigellosis and gonorrhea, and travel history concerning for direct and indirect Shigella exposure.” ¹ We further state that “Regardless of travel history, shigellosis should be considered in cases of acute gastroenteritis or proctocolitis given the range of potential transmission pathways.” ¹

Regarding multidrug-resistant (MDR) shigellosis in the MSM population, specifically, we concur with Taylor et al. that this is of increasing concern. As stated in our paper, “Within Shigella isolates collected from the MSM population in the United Kingdom (UK), high rates of azithromycin resistance and outbreaks of S. flexneri 3a, S. flexneri 2a and S. sonnei have been reported.^4,5 Outbreaks of multi-drug resistant (MDR) S. sonnei outbreaks have been documented in Montreal, and S. flexneri serotype 1 in Vancouver, within the Canadian MSM population.”^6,7 Such emerging trends underscore the need for ongoing surveillance of AMR, and in particular, stratification of surveillance data with sufficient granularity as to inform epidemiologically based clinical decision-making. As stated in our paper, “Targeted antimicrobial therapy against Shigella spp. infection for individuals living with HIV is recommended. ⁸ In those with CD4 > 500 cells/mm³ where diarrhea resolves before culture confirmation, antimicrobial therapy may be withheld. In other cases where culture positivity is rendered during clinical illness, therapy should be offered ideally using ciprofloxacin for 7–10 days for isolates with MICs < 0.12 µg/mL.^8,9” Our clinical decision-making is supported not just by national-level guidance, but also by both local hospital-based antibiogram data^10,11 and reference laboratory surveillance data, available through Public Health Ontario. ¹² From such sources, we know that the vast majority of Enterobacteriaceae isolates seen in ambulatory patients at our center are susceptible to fluoroquinolones.^10,11 Moreover, we know that in the Province of Ontario (population > 16,000,000), 85% of S. flexneri isolates are resistant to ampicillin, 65% are resistant to TMP-SMX, 49% are resistant to azithromycin, and 34% are resistant to ciprofloxacin. ¹² As such, fluoroquinolones represented the best empiric choice for oral therapy when encountering such an ambulatory patient with probable travel-acquired and possibly sexually acquired S. flexneri infection. Reassuringly, of all extensively drug-resistant (XDR) isolates of Shigella identified through provincial surveillance, only 25% were reported among those engaging in same-sex sexual activity and all were S. sonnei. ¹² No cases of XDR S. flexneri were identified in provincial surveillance in the years following 2020. ¹² Moreover, the proportion of Shigella infections with XDR was equally distributed across male and female sex at 3.6% (27/740 and 12/332, respectively). ¹² Finally, we know through provincial surveillance that only 6% of travel-acquired XDR cases of shigellosis were reported from Europe, the region to which our patient had traveled. ¹² As such, based on the totality of antimicrobial resistance surveillance data in Shigella isolates and Enterobacteriaceae available to us, the patient’s clinical picture, planned close follow-up, and personal clinical experience in the care of such patients, we had every confidence that an initial short course of ciprofloxacin was likely to lead to significant clinical improvement. While we agree that oral fosfomycin and/or pivmecillinam following IV meropenem are step-down options for cases of XDR shigellosis in which symptoms are severe, we respectfully suggest that sufficiently robust data supporting their first-line use in mild cases of shigellosis that are unlikely to be XDR are lacking. ¹³ Furthermore, given the probable travel-acquired nature of our patient’s diarrheal illness, erring on the side of conforming to robust clinical practice guidelines regarding selection of antimicrobials was prudent and consistent with the standard of care.^14,15 We certainly agree that robust local and global surveillance data are required to best inform clinical care. While at the time of care, antimicrobial susceptibilities were not reported by the laboratory for this particular stool isolate of Shigella, based on the emerging AMR trends noted by Taylor and colleagues and in our paper, it is now standard practice for such information to accompany the species identification report. ¹⁶ Following direct request to the reference laboratory, susceptibility testing has now occurred, and the S. flexneri isolate has been reported as resistant to ampicillin and azithromycin, and susceptible to ceftriaxone, ciprofloxacin, levofloxacin, and trimethoprim–sulfamethoxazole.

We thank Taylor and colleagues for highlighting the need to screen for other STIs in such patients, a recommendation with which we fully concur. As stated in our paper, “Given . . .. . . overlapping symptoms, screening for parasitic, enteric and STI infections are important to identify possible polymicrobial infections in this population.” ¹⁷ As further stated, “There is transmission risk, incubation, and symptomatic overlap between common STIs, especially rectal infections, and shigellosis; as such, the differential diagnosis should remain broad to account for intercurrent infections and reducing the risk of premature diagnostic closure.” As noted in our paper, testing for HSV-1 and HSV-2 was negative, as was Chlamydia screening. We are fortunate to have access to test results ordered by other clinicians in our region through shared medical record systems, and as such, we were aware of the patient’s other screening results, which, while not explicitly reported in our manuscript, were non-contributory to the case. As evidenced by his effective suppressive antiretroviral therapy, his active engagement in ongoing primary care, including but not limited to age-appropriate screening and preventive interventions such as vaccines and doxycycline prophylaxis, is understood to exist.

We further thank Taylor and colleagues for identifying the need for behavioral-specific counseling following a diagnosis of possible sexually acquired shigellosis, with which we also agree. As stated in our manuscript, “Following treatment for shigellosis, the other management consideration in this patient was advice regarding infection prevention and control. CDC recommends waiting at least 2 weeks post-diarrhea resolution before engaging in any form of sexual intercourse given this risk of transmission. ⁹ Other groups recommend hand washing and avoiding sexual contact for 1 week after complete resolution of symptoms. ¹⁸ In our case, Toronto Public Health communicated infection control practices for our patient, however, it is important for health care providers to be aware of these recommendations and to discuss with their patients to aide in outbreak prevention.” ¹ In our province, both Shigella spp. infections and gonorrhea are notifiable diseases and, as such, generate automatic engagement of public health follow-up upon microbiological diagnosis or physician report. ¹⁹ Such follow-up entails individual case contact to elicit travel-, food-, and exposure history; educate on the risks of transmission; and advise around appropriate infection prevention and control practices.^20,21 We further state in our manuscript that “Individuals diagnosed with shigellosis should be counselled at the time of diagnosis around behaviors that will reduce or prevent transmission.” ¹ Taylor and colleagues should be congratulated on their contributions to the British Association of Sexual Health and HIV (BASHH) United Kingdom national guideline for the management of sexually transmitted enteric infections 2023, ²² which highlight the important and clinically impactful additional public health measures noted in their letter, including but not limited to pre-exposure preventive interventions and vaccination against human papillomavirus and Mpox. We further concur that continued surveillance for MDR and XDR isolates of Shigella with ideally iterative incorporation of surveillance data into clinical guidelines will optimize best practices in clinical care, particularly for at-risk populations such as MSM.