A 35-year-old man comes to the emergency department due to urinary urgency, a burning sensation on urination, and urethral discharge. The patient had similar symptoms 3 months ago, and urethral swab microscopy showed numerous neutrophils and intracellular gram-negative diplococci. The symptoms resolved after treatment with ceftriaxone and doxycycline but recurred 4 days ago. The patient was advised to use condoms but has had unprotected sexual encounters recently. He has no other medical conditions. The patient occasionally drinks alcohol and smokes cigarettes. Temperature is 37.1 C (98.8 F). BMI is 18.8 kg/m². No suprapubic or flank tenderness is present. Mild erythema is noted at the urethral meatus. Nucleic acid amplification testing of a clean catch urine specimen is positive for Neisseria gonorrhoeae and negative for Chlamydia trachomatis. Which of the following is the most likely reason for the recurrence of infection in this patient?

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11ec160b_3865_a748_9249_f1847bd78599_MD0001_00 This young patient who engages in high-risk sexual activity developed dysuria, frequency, and urethral discharge 3 months ago, indicating infectious urethritis. Gram stain at that time showed intracellular gram-negative diplococci, which is diagnostic for Neisseria gonorrhoeae infection. Because coinfection with N gonorrhoeae and Chlamydia trachomatis is common, and because Chlamydia cannot be seen on Gram stain due to lack of peptidoglycan in the cell wall, the patient was treated empirically for both infections with ceftriaxone and doxycycline. Although treatment resolved the symptoms completely, the patient developed recurrent manifestations after additional unprotected sexual encounters, raising suspicion for N gonorrhoeae reinfection. Gonorrhea infection generates IgA and IgG antibodies against the bacteria; however, these antibodies provide limited or no protective immunity against future infections due to an extremely high rate of antigenic variation in bacterial surface molecules (eg, porins, Opa proteins, lipooligosaccharide). (Choice A) Memory T cells form in response to gonococcal infection but are not effective at preventing reinfection due to high antigenic variation, which prevents recognition of antigens from the organism. (Choice B) The humoral antibody response can be impaired by severe malnutrition; however, the high rate of antigenic variability in gonococcal infection would already preclude development of an effective antibody response. (Choice D) Antigenic mimicry occurs when an organism displays similar antigens to the host, preventing the host's immune system from recognizing the organism as foreign. (Choice E) Gonorrhea is largely susceptible to third-generation cephalosporins (eg, ceftriaxone) but may be resistant to penicillins, macrolides, and fluoroquinolones. Antibiotic resistance should be suspected when initial symptoms do not improve with treatment. Because this patient's initial symptoms resolved after he was treated with ceftriaxone and then recurred a few months later, reinfection is far more likely than drug resistance. Educational objective: Neisseria gonorrhoeae has high antigenic variability of surface molecules (eg, porins, Opa proteins, lipooligosaccharide), which prevents the formation of protective immunity and leads to susceptibility to repeat infection. __________ References: New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host. (http://www.ncbi.nlm.nih.gov/pubmed/21833308)

A 35-Year-Old Man Comes to the Emergency Department Due to Urinary