chronic.html
CASE STUDY
Chronic genital ulcer disease with subsequent development of methicillin-resistant Staphylococcus aureus (MRSA) urethritis and bacteraemia in an HIV-seropositive person – a case observation
Christine Katusiime,
MB ChB, PGDPPM, MIPH
Andrew Kambugu,
MB ChB, MMed
Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda
HIV-seropositive persons are at increased risk of methicillin-resistant
Staphylococcus aureus (MRSA). Genital ulcerative disease and sexually
transmitted infection with subsequent MRSA infection in
HIV-seropositive persons have been documented only once. We report a
case of a 44-year-old man who presented to the Infectious Diseases
Institute, Kampala, Uganda, with chronic genital ulcer disease and who
subsequently developed MRSA urethritis and bacteraemia. This case also
demonstrates that persistent genital ulcer disease in HIV-seropositive
persons may be as a result of concurrent MRSA infection.
HIV-seronegative persons are less likely to become infected with Staphylococcus aureus and associated S. aureus septicaemia than their HIV-seropositive counterparts.1
,
2 Studies have demonstrated an increased risk of MRSA infection among HIV-seropositive persons of up to 18 times.3
MRSA infection therefore presents a public health concern. MRSA
infection has also been found to be associated with sexually
transmitted infections (STIs) and genital ulcer disease (GUD) in
HIV-seropositive persons.6 GUD with associated MRSA infection has only been documented once.6
The case we present in this report is of chronic genital ulceration
complicated by MRSA urethritis and bacteraemia. This case of chronic
GUD with subsequent MRSA infection in an HIV-seropositive host also
highlights the importance of ruling out concurrent MRSA infection in
chronic GUD in HIV-seropositive persons.
Case presentation
A 44-year-old HIV-seropositive man with World Health Organization
(WHO) stage IV disease, who had been on highly active anti-retroviral
therapy (HAART) of tenofovir, lamivudine and efavirenz, and
co-trimoxazole prophylaxis since March 2008, presented with an 8-month
history of genital ulceration and a 4-month history of urethral pus
discharge. He initially noticed a small papule on the glans of his
penis which increased in size and ulcerated. He subsequently developed
a yellow non-odorous urethral discharge. On review of symptoms, he
denied associated fevers and chills, or trauma to the site. He had no
significant previous medical history and denied cigarette smoking,
alcohol consumption and intravenous drug usage. He was heterosexual,
denied unsafe sexual practices, and had no history of previous STIs,
antibiotic use, and recurrent STIs or GUD.
Physical examination revealed a body temperature of 36.1oC,
pulse rate 86 beats per minute, blood pressure 120/70 mmHg, and
respiratory rate 12 breaths per minute. Genital examination revealed an
ulcer involving the glans of the penis with a yellow urethral
discharge. Precordial, ophthalmic, gastrointestinal and respiratory
examinations were unremarkable. Neurologically, there were no cranial
nerve deficits, reflexes were symmetrical and normal, and distal
sensation was intact.
Laboratory data revealed a white blood cell (WBC) count of
5 000/mm3 and an elevated
erythrocyte sedimentation rate (ESR) of 80 mm/hr. His urine revealed
500 leukocytes/ul, trace protein, 66 white blood cells/high-power field
(hpf) and 1 cast/hpf. The rest of the routine laboratory tests
including renal function tests, liver function tests, random blood
sugar (RBS), Treponemal pallidum
haemagglutination assay (TPHA), serum cryptococcal antigen (CRAG)
titres, hepatitis B surface antigen (HBsAg) and brucella agglutination
assay were unremarkable. CD4+ cell counts were 944 cells/mm3
(30%), and plasma HIV RNA levels were undetectable. Herpes simplex
virus-2 (HSV-2) serology could not be done because of the high costs
involved.
A penile wedge biopsy taken for histopathological examination
showed features suggestive of a chronic penile ulcer. The urethral pus
swabs and blood cultures grew MRSA sensitive to gentamicin,
ciprofloxacin and vancomycin but resistant to oxacillin, tetracycline,
penicillin and erythromycin. Urine cultures depicted no growth. A
clinical diagnosis of chronic ulcerative genital herpes was made,
following consultation with an STD specialist. The patient was then
admitted and commenced on a course of oral acyclovir 400 mg twice daily
for 6 months and intravenous vancomycin for 2 weeks for chronic
ulcerative genital herpes and MRSA urethritis and bacteraemia
respectively. Intravenous ceftriaxone was also administered to treat
the urinary tract infection (UTI). Continual adherence to
co-trimoxazole, acyclovir and HAART was continually emphasised.
The course of treatment was successful; examination at 1 month and 2
months follow-up revealed no urethral discharge and completely healed
penile ulcerations.
Discussion
HIV-infected persons have a higher risk of MRSA infection than the general population. 3 The reason why our patient was predisposed to MRSA infection could have been a result of the chronic genital ulceration.
Prior studies have implicated lack of co-trimoxazole prophylaxis,
intravenous drug usage, low CD4 T-cell count, high HIV viral load and
hospitalisation as risk factors for MRSA colonisation in
HIV-seropositive patients.10
These factors, however, were not noted in our patient. Ramsetty and
colleagues demonstrated that HIV-seropositive patients with CD4 T-cell
counts <200 cells/mm3 were at significant risk of MRSA infections.13 Our patient was the exception to this finding, as his CD4 T-cell count was 944 cells/mm3 .
A ramification of this case is the importance of considering
concurrent MRSA infection in HIV-seropositive patients with chronic
GUD. Other factors that make this case unique are the development of
MRSA urethritis and bacteraemia despite the patient’s high CD4
T-cell counts and good virological control.
Conclusion
Our patient developed MRSA infection following chronic GUD
that was not effectively managed. Clinicians need to maintain vigilance
in the management of chronic GUD in HIV-seropositive persons, as MRSA
co-infection may become an increasing complication in the future.
REFERENCES
1. Enthilkumar A, Kumar S, Sheagren J. Increased
incidence of Staphylococcus aureus bacteremia in hospitalized patients
with acquired immunodeficiency syndrome. Clin Infect Dis
2001;33:1412-1416.
1. Enthilkumar A, Kumar S, Sheagren J. Increased
incidence of Staphylococcus aureus bacteremia in hospitalized patients
with acquired immunodeficiency syndrome. Clin Infect Dis
2001;33:1412-1416.
2. Weinke T, Schiller R, Fehrenbach FJ, Pohle HD.
Association between Staphylococcus aureus nasopharyngeal colonization
and septicemia in patients infected with the human immunodeficiency
virus. Eur J Clin Microbiol Infect Dis 1992;11:985-989.
2. Weinke T, Schiller R, Fehrenbach FJ, Pohle HD.
Association between Staphylococcus aureus nasopharyngeal colonization
and septicemia in patients infected with the human immunodeficiency
virus. Eur J Clin Microbiol Infect Dis 1992;11:985-989.
3. Matthews WC, Caperna JC, Barbaer RE, et al.
Incidence of and risk factors for clinically significant
methicillin-resistant Staphylococcus aureus infection in a cohort of
HIV infected adults. J Acquir Immune Defic Syndr 2005;40:155-160.
3. Matthews WC, Caperna JC, Barbaer RE, et al.
Incidence of and risk factors for clinically significant
methicillin-resistant Staphylococcus aureus infection in a cohort of
HIV infected adults. J Acquir Immune Defic Syndr 2005;40:155-160.
4. Crum-Cianflone NF, Burgi AA, Hale BR.
Increasing rates of community-acquired methicillin-resistant
Staphylococcus aureus infections among HIV-infected persons. Int J STD
AIDS 2007;18:521-526.
4. Crum-Cianflone NF, Burgi AA, Hale BR.
Increasing rates of community-acquired methicillin-resistant
Staphylococcus aureus infections among HIV-infected persons. Int J STD
AIDS 2007;18:521-526.
5. Popovich KJ, Weinstein RA, Aroutcheva A, Rice
T, Hota B. Community-associated methicillin-resistant Staphylococcus
aureus and HIV: Intersecting Epidemics. Clin Infect Dis 2010;50:979-987.
5. Popovich KJ, Weinstein RA, Aroutcheva A, Rice
T, Hota B. Community-associated methicillin-resistant Staphylococcus
aureus and HIV: Intersecting Epidemics. Clin Infect Dis 2010;50:979-987.
6. Crum-Cianflone NF, Shadyab AH, Weintrob A, et
al. Association of methicillin-resistant Staphylococcus aureus (MRSA)
colonization with high-risk sexual behaviors in persons infected with
human immunodeficiency virus (HIV). Med 2011;90:379-389.
6. Crum-Cianflone NF, Shadyab AH, Weintrob A, et
al. Association of methicillin-resistant Staphylococcus aureus (MRSA)
colonization with high-risk sexual behaviors in persons infected with
human immunodeficiency virus (HIV). Med 2011;90:379-389.
7. Burkey MD, Wilson LE, Moore RD, Lucas GM,
Francis J, Gebo KA. The incidence of and risk factors for MRSA
bacteraemia in an HIV-infected cohort in the HAART era. HIV Med
2008;9:858-862.
7. Burkey MD, Wilson LE, Moore RD, Lucas GM,
Francis J, Gebo KA. The incidence of and risk factors for MRSA
bacteraemia in an HIV-infected cohort in the HAART era. HIV Med
2008;9:858-862.
8. Cenizal MJ, Hardy RD, Anderson M, Katz K,
Skiest DJ. Prevalence of and risk factors for methicillin-resistant
Staphylococcus aureus (MRSA) nasal colonization in HIV-infected
ambulatory patients. J Acquir Immune Syndr 2008;48:567-571.
8. Cenizal MJ, Hardy RD, Anderson M, Katz K,
Skiest DJ. Prevalence of and risk factors for methicillin-resistant
Staphylococcus aureus (MRSA) nasal colonization in HIV-infected
ambulatory patients. J Acquir Immune Syndr 2008;48:567-571.
9. Diep BA, Chambers HF, Graber CJ, et al.
Emergence of multidrug-resistant community-associated
methicillin-resistant Staphylococcus aureus clone USA300 in men who
have sex with men. Ann Intern Med 2008;148:249-257.
9. Diep BA, Chambers HF, Graber CJ, et al.
Emergence of multidrug-resistant community-associated
methicillin-resistant Staphylococcus aureus clone USA300 in men who
have sex with men. Ann Intern Med 2008;148:249-257.
10. Sissolak D, Geusau A, Heinze G, Witte W,
Rotter ML. Risk factors for nasal carriage of Staphylococcus aureus in
infectious disease patients, including patients infected with HIV, and
molecular typing of colonizing strains. Eur J Clin Microbiol Infect Dis
2002;21:88-96.
10. Sissolak D, Geusau A, Heinze G, Witte W,
Rotter ML. Risk factors for nasal carriage of Staphylococcus aureus in
infectious disease patients, including patients infected with HIV, and
molecular typing of colonizing strains. Eur J Clin Microbiol Infect Dis
2002;21:88-96.
11. Szumowski JD, Wener KM, Gold HS, et al.
Methicillin-resistant Staphylococcus aureus colonization, behavioral
risk factors, and skin and soft-tissue infection at an ambulatory
clinic serving a large population of HIV-infected men who have sex with
men. Clin Infect Dis 2009;49:118-121.
11. Szumowski JD, Wener KM, Gold HS, et al.
Methicillin-resistant Staphylococcus aureus colonization, behavioral
risk factors, and skin and soft-tissue infection at an ambulatory
clinic serving a large population of HIV-infected men who have sex with
men. Clin Infect Dis 2009;49:118-121.
12. Villacian JS, Barkham T, Earnest A, Paton NI.
Prevalence of and risk factors for nasal colonization with
Staphylococcus aureus among human immunodeficiency virus-positive
outpatients in Singapore. Infect Control Hosp Epidemiol 2004;25:438-440.
12. Villacian JS, Barkham T, Earnest A, Paton NI.
Prevalence of and risk factors for nasal colonization with
Staphylococcus aureus among human immunodeficiency virus-positive
outpatients in Singapore. Infect Control Hosp Epidemiol 2004;25:438-440.
13. Shet A, Mathema B, Mediavilla JR, et al.
Colonization and subsequent skin and soft tissue infection due to
methicillin-resistant Staphylococcus aureus in a cohort of otherwise
healthy adults infected with HIV type 1. J Infect Dis 2009;200:88-93.
13. Shet A, Mathema B, Mediavilla JR, et al.
Colonization and subsequent skin and soft tissue infection due to
methicillin-resistant Staphylococcus aureus in a cohort of otherwise
healthy adults infected with HIV type 1. J Infect Dis 2009;200:88-93.
14. Ramsetty SK, Stuart LL, Blake RT, Parsons CH,
Salgado CD. Risks for methicillin-resistant Staphylococcus aureus
colonization or infection among patients with HIV infection. HIV Med
2010;11:389-394.
14. Ramsetty SK, Stuart LL, Blake RT, Parsons CH,
Salgado CD. Risks for methicillin-resistant Staphylococcus aureus
colonization or infection among patients with HIV infection. HIV Med
2010;11:389-394.
Fig. 1. Ulceration and yellow penile urethral discharge.
Fig. 2. Ulceration involving entire glans.