Directed antimicrobial prophylaxis in recipients has been shown to be effective in preventing transmission of multidrug-resistant Gram-negative pathogens. In a case report from the United States, Ariza-Heredia et al describe the use of organs from a donor known to be infected with carbapenem-resistant K. pneumoniae before organ procurement. The donor was a 21-year-old man who sustained multiple injuries in a motor vehicle accident and was hospitalized for approximately 3 weeks before being declared brain dead. He developed pneumonia during treatment, an infected subdural hematoma, and meningitis due to carbapenem-resistant K. pneumoniae, although blood cultures remained negative. The donor was treated with IV tigecycline for 9 days and received 3 doses of intrathecal gentamicin at the time of death. As cultures were still positive for carbapenem-resistant K. pneumoniae at the time of death, the transplant teams were informed and specific consent sought from the potential recipients and their families. The liver, kidneys, heart, and a vein graft were retrieved. The recipient of the right kidney received pretransplant doses of IV gentamicin (4 mg/kg) and tigecycline (100 mg), and posttransplant received a 10-day course of IV tigecycline (50 mg every 12 hours). Surveillance cultures of the preservation fluid were negative, and 5 months posttransplant, the recipient was doing well. The heart recipient received perioperative IV cefepime (2 g every 12 hours) and tigecycline (100 mg loading does then 50 mg twice daily). Antimicrobial prophylaxis received posttransplant included valacyclovir, trimethoprim-sulfamethoxazole, and inhaled amphotericin B, and cultures remained negative for carbapenem-resistant K. pneumoniae.
The recipient of the liver and kidney in the case reported by Ariza-Heredia developed a postoperative infected hematoma and peritonitis due to carbapenem-resistant K. pneumoniae, despite receiving prophylaxis with IV tigecycline (initial loading dose of 100 mg, followed by 50 mg every 12 hours planned for 2 weeks). On posttransplant day 10, the patient developed severe abdominal pain, tenderness and leukocytosis, and cultures of the ascetic fluid were positive for carbapenem-resistant K. pneumoniae. The patient underwent exploratory laparotomy and washout, and IV amikacin was added to the treatment regimen, along with ciprofloxacin for possible synergy, and fluconazole to treat a concurrent Candida albicans infection. On day 24, cultures were still positive for carbapenem-resistant K. pneumoniae, and the treatment regimen was changed to meropenem (1 g IV every 8 hours), amikacin (500 mg IV every 12 hourly), ampicillin (1 g IV every 6 hours), and fluconazole (200 mg p.o. daily) for 4 weeks. Five months posttransplantation, the recipient showed no recurrence of infection.
Source control is the first priority in the treatment of multidrug-resistant bacteria, including drainage of collections and the removal of any infected devices. The choice of antimicrobial treatment and dosage should take into account pathogen susceptibility profile and local resistance patterns, predicted drug levels at the site of the infection, cost, method of administration, side-effect profile, severity of infection, and any know multidrug-resistant colonizers in the recipient. Treatment recommendations for multidrug-resistant gram-negative bacteria infections in solid organ transplant recipients are given in Table 31.
The number of cases of infectious syphilis reported in Australia in 2016 was 3367, of which 87% of diagnoses were in males and 16% were in ATSI persons. In the non-Indigenous population, male-to-male sex is the primary transmission route, and over 90% of all notifications of infectious syphilis are in males (see Figure 13). In contrast, only 54% of infectious syphilis notifications in ATSIs in 2006 were in males. The infectious syphilis notification rate in Australia increased 107% from 2012 to 2016 (from 6.9 to 14.3 cases per 100 000), driven largely by increased transmission among MSM and by an ongoing outbreak of infectious syphilis among ATSI people living in northern Australia. This outbreak began in northern Queensland in January 2011, spread to the Northern Territory in July 2013, and to the Kimberley region of Western Australia in June 2014. An outbreak in the western, Eyre and far north regions of South Australia was declared in March 2017. By 2016, the infectious syphilis notification rate in the ATSI population living in remote and very remote areas was 135.4 per 100 000:50.1 times higher than the rate in the non-Indigenous population. Also of note, this outbreak has primarily affected young ATSI people:in 2016, 21% of infectious syphilis notifications in the ATSI population were in the 15- to 19-year age group, compared to only 2% of the non-Indigenous population.
In New Zealand there has also been a steady increase in infectious syphilis cases since 2002, with a notable jump in notifications from 2013 to 2014 (from 82 to 140 cases). As in Australia, the vast majority of cases (>90%) are in males, and male-to-male sex is the primary transmission route (approximately 90% of cases). The majority ethnicity reported in MSM cases was NZ European (57% in 2014), followed by Asian (13%), Maori (13%), other (12%), and Pacific Islanders (3%). Cases are concentrated among males aged 20 to 34 years, with the biggest increase in cases since 2011 occurring among males aged 20 to 24 years. The Auckland region reported the highest number of infectious syphilis notifications in 2014 (61% of the total).
Historically, syphilis screening has been based on nontreponemal serological tests:either the RPR or Venereal Disease Research Laboratory (VDRL) test:which are sensitive in newly infected individuals but can produce false-positive results due to factors such as other infections (eg, HIV), autoimmune conditions, injecting drug use, or other causes of inflammation or immunological reactivity. In a retrospective study of RPR-positive deceased donors, Theodoropoulos et al demonstrated a false-positive rate of 40.6% for RPR tests. Treponemal-specific tests have greater specificity but continue to yield positive results after successful treatment. The United States Centers for Disease Control specify that a diagnosis of syphilis requires positive results on both a nontreponemal test and a treponemal-specific test. Treponemal-specific tests include FTA-ABS tests, the TP-PA) assay, various EIAs, chemiluminescence immunoassays, immunoblots, or rapid treponemal assays. Test performance characteristics of available syphilis tests, versus TP-PA as the gold standard, are given in Table 32.
The conventional approach to screening has been to test first with a nontreponemal test and then confirm positive results with a treponemal-specific test, though more recently there has been a shift to a "reverse-sequence" approach, whereby an initial treponemal-specific test is followed by a nontreponemal test to confirm positive results. Current international guidelines and state-based guidelines in Australia recommend routine screening of deceased donors for syphilis infection using a treponemal-specific EIA, with confirmation by a nontreponemal serological test. If the nontreponemal test is negative, then a second treponemal test based on different antigens to the original test should be performed. This reverse sequence approach has the advantage of being able to distinguish potential donors who have been previously treated for syphilis, those with untreated or incompletely treated syphilis, and those with a false-positive result. Treponemal test results should be interpreted in the context of what is known about the donor's history of treatment for syphilis and their sexual history, because there is always the possibility that previously treated persons may have a new, recently reacquired syphilis infection.
A positive syphilis test does not necessarily preclude organ donation; however, newly diagnosed syphilis indicates that the donor is also at increased risk of having recently acquired HIV, HBV, or HCV, and decisions regarding utilization should be made accordingly. If the decision is made to proceed with transplantation, then the recipient will require appropriate treatment.
Only 4 cases of syphilis transmission via organ donation have been reported:1 confirmed transmission reported to the United States OPTN, and 3 reports in the published literature. In a 2003 case, a homosexual male with a history of treated syphilis donated kidneys to 2 recipients. Donor syphilis serology, available only after transplantation had taken place, was reactive on TP-PA (titer, 1:1280) and RPR (titer, 1:2), which was interpreted as consistent with a history of treated infection. The 2 recipients were informed and were administered a single dose of 2.4 g IV benzyl penicillin instead of the recommended benzathine penicillin 2.4 MU administered intramuscularly. Recipient serum samples collected on day 5 posttransplant were reactive on treponemal EIA, and both recipients were then treated for early latent syphilis according to the 2002 UK guidelines. After 2 years of follow up, both recipients had excellent kidney function, and 3 monthly RPR tests remained negative.