control and prevention of HIV/AIDS

The Intersection of HIV/AIDS and Community Acquired Methicillin Resistant Staphylococcus Aureus (CAMRSA)

Marci English

Advanced Topics in the Control and Prevention of HIV/AIDS



Staphylococcus aureus (SA) is a common bacterial pathogen associated with a wide spectrum of infections.1 23 In recent years, methicillin resistant S. aureus (MRSA) has become more prevalent, and has obtained significant attention due to the limited effective treatments.4,5 Another resistant clonal variant of SA, community-acquired methicillin resistant Staphylococcus aureus (CAMRSA), is emerging as a serious pathogen among the general population.2,4

CAMRSA arose independently in the community and is not simply a variant of healthcare associated MRSA (HAMRSA).3,5 Multiple publications have recently examined risk factors for CAMRSA infections among HIV positive patients. These researchers have also examined various subpopulations within the HIV positive community to elucidate additional risk. Several recent case studies have examined infections seen in the HIV community that may serve as harbingers of HIV infection in those previously undiagnosed. These studies and case reports will be summarized herein. The rise of CAMRSA within the HIV positive community merits concern and focus, as infections are likely to become more common in the future within this population. Knowledge and awareness among clinicians and additional research may result in better clinical outcomes for these patients.

General Epidemiology and Microbiology of CAMRSA: Differentiation from HAMRSA6

It is important to differentiate between HAMRSA and CAMRSA. HAMRSA is associated with contact with the health care system (i.e., long term care resident, healthcare worker, recent hospitalization or surgical procedure), prior antibiotic use, co-morbidities such as diabetes or other chronic illnesses, ICU admission, ventilator use, indwelling devices, and hemodialysis1,1,7,8. Conversely, CAMRSA was initially characterized as MRSA infections presenting in the community among healthy individuals with no known risk factors or recent hospital interaction. 1,5,8 These lines are becoming blurred however, as CAMRSA (USA 300 strain specifically) is on the rise globally, and there are indications that this strain will become more prevalent in the hospital setting. 4,9

HAMRSA and CAMRSA can be differentiated by phenotypic and genotypic profiling.5 Classification of strains has been recently standardized by employing pulse field gel electrophoresis (PFGE) to detect the staphylococcal chromosomal cassette and efforts to use an official naming system established by CDC which refers to strains as "USAxxx".10 For brevity, contrasting features between HAMRSA and CAMRSA are further summarized in Appendix A.

Some general CAMRSA risk factors and target populations have been elucidated by epidemiological study. CAMRSA was initially reported in small outbreaks in Australia,11 Minnesota/North Dakota12, and Chicago13 in otherwise healthy individuals. These outbreaks were unusual in that these individuals had no recent, documented contacts with health care services. Surveillance for CAMRSA has revealed associations with specific community groups, including but not limited to men who have sex with men (MSM)14-17, prison populations18 the homeless,19 military personnel,18 day care attendees,20 certain athletic sport participants,10,21 and, in one of the more media-covered outbreaks, professional athletes.22 Increasing study pertaining to these groups and their HIV status, particularly MSM and intravenous drug users, is attempting to elucidate additional risk factors associated with CAMRSA infection.

The global distribution of CAMRSA is still evolving, including in HIV+s. In the US, it is confirmed that infections and colonizations among HIV+s are increasing, with some facilities reporting CAMRSA infection rates in HIV+s that are 18-fold higher as compared to the general population.23 However, a recent European studies evaluating MRSA infections concluded that CAMRSA isolates were infrequently a cause of infection or colonization in their HIV+ patient cohorts.24-26 This may indicate that European outbreaks are in their infancy. Most worrisome is the potential for this epidemiological data to create a laxity in attitude regarding the possibility of a CAMRSA outbreak. Therefore, caution is warranted for those regions with little evidence of currently circulating CAMRSA, as the epidemic USA300 strain has demonstrated easy transmission and rapid circulation.19

Clinical Presentation and Pathology of CAMRSA in the General Population

CAMRSA infections predominantly manifest in uncomplicated or complicated skin and soft tissue infections (SSTIs). 1,27 Less frequently, it can cause respiratory syndromes such as necrotizing pneumonia,28 necrotizing fasciitis,29,30 sepsis,31 bacteremia,32 and endocarditis.33 The general characteristics of the clinical presentation of HAMRSA as compared to CAMRSA are outlined in Appendix B.

Clinical Presentation of CAMRSA in the HIV positive community

HIV+ patients are disproportionately affected by CAMRSA infections in terms of frequency, but the clinical presentation of the infections is similar to the general population overall.23,34 Abscesses and other SSTIs are most common.35 Folliculitis has a common etiology of CAMRSA in any population; however, eosinophilic follicultis is common in HIV+ patients with low CD4+ counts.36 It can be difficult to distinguish this non-infectious syndrome from a CAMRSA infection; thus clinicians should be aware of the possibility of CAMRSA causing this pathology. This is especially important if a patient has a follicular rash and has not recently started ART, as eosinophillic folliculitis is sometimes seen soon after ART therapy has commenced.36 Several unique clinical presentations of MRSA may aide in the initial HIV diagnosis and are discussed later in this summary.

What are The Risk Factors for CAMRSA Infection in HIV+ Patients?

Most of the data collected on risk factors for CAMRSA infection in HIV+s focus on retrospective cohorts or case-control studies. Generally, evaluated risk factors fall into two groups: those that relate to belonging to a particular group or participating in a particular behavior, or those that are co-morbidities (e.g., colonization) and/or associated with the pathology of the HIV infection. There are limitations to this data, in that the sample sizes are often very small and the results of such studies often produce conflicting data, as will be discussed. Large, prospective cohort studies are needed to further evaluate risk factors for CAMRSA in HIV+s.

Sub-populations and Behavioral Risk Factors

Men who have sex with men (MSM) are at increased risk of CAMRSA infection that results primarily in SSTIs with high rates of recurrence.37 In a retrospective study examining HIV+ MSM in two geographically independent communities, having male-male sex increased the risk of a USA 300 infection by 12-fold, with most of the USA 300 strains exhibiting multidrug resistance. 16 The infections involved the buttocks and/or genital area more frequently than other parts of the body, indicating that the infection may have been transmitted during sexual contact. 16 Interestingly, in a multivariate model, HIV status did not impact risk for acquisition of a MDR strain of USA 300.16 It has been suggested by other researchers that practitioners focused on sexual health need to be aware of the potential for CAMRSA to appear in their patient populations.38 Lee et al demonstrated that risk factors for CAMRSA associated with MSM typically involve subpopulations that participate in high risk activities, such as IDU and high risk sexual practices; however, immune status was not related to risk of infection.17 In contrast to other studies, ART and sexual contact was not related to the risk of infection. 17 Clearly, MSM risk factors need further study, however it may be true that HIV and immune status are not the leading factors for acquisition of infection in MSM.

Intravenous drug users (IDUs) are a group that is commonly HIV+, and IDU is a potential risk factor for CAMRSA infection. 37,39 This is logical, as IDUs by nature of the delivery of illicit drugs create wounds from which bacteria gain entry for subsequent infections. One examination of IDUs that were either HIV+ or HIV- indicated that there were no HIV-specific risk factors associated with SA colonization. 39 However, this study obtained very few MRSA isolates, with most being MSSA (a common IDU infection due to skin carriage), but the few MRSAs that were isolated were most commonly from HIV+ IDUs.39 A case of xanthogranulomatous pyelonephritis caused by CAMRSA in an HIV-infected IDU emphasizes the need for practitioners to expand what causative pathogens they consider when treating infections in IDUs.40

Patients with HIV often develop renal insufficiency and need hemodialysis.41 Epidemiological study of renally compromised HIV+ patients requiring hemodialysis demonstrates an increase in the number of vascular access associated CAMRSA infections.7 Specific case reports of HIV+s acquiring MRSA infections from hemodialysis treatment exist in the literature; however the report in question did not characterize the isolate as HAMRSA or CAMRSA.41 However, these facts in their entirety may indicate that hemodialysis is a potential risk factor for HIV+s, especially if CAMRSA strains continue to appear in the hospital setting.

Co-morbid Conditions and Other Therapies May Modify Risk

Decreased CD4+ cell counts are implicated as a risk factor for CAMRSA infection 23, but in some populations this association is not seen.17 It makes sense from a biological perspective that an immunocompromised patient would be at risk for opportunistic infections, including CAMRSA. However, a retrospective study of MSM in New York City to determine risk factors for recurrence of CAMRSA infections found that most of their HIV positive patients with CAMRSA infections had CD4+ counts above 200. {{}} Additionally, in the IDU study performed by Miller et al, no relationship between SA colonization and immunosuppression was found, but colonized individuals harbored predominantly MSSA isolates.42 Clearly other factors that have not yet been elucidated may be at play. It is important to note that these studies had very small sample sizes.

Viral load has been implicated as a risk factor, but only the maximum viral load has been associated with CAMRSA, rather than current viral load as measured at the time of the infection.23,43,44,44 The role of viral load is still unclear however, as other studies have not seen this association. 17

It may be that this conflicting data regarding immune status and CAMRSA risk in HIV+ persons is not truly discrepant. Surveys of studies by Thompson et al propose that CAMRSA may end up becoming one of the typical opportunistic infections seen in HIV+ individuals, much like TB or Kaposi's sarcoma. While infections can occur at any viral load or CD4 count, it may be that when viral load is very high or CD4 count is very low, these infections (CAMRSA included) are simply much more severe. 45

Prior antibiotic use within the past 6months-1 year has been linked with increased CAMRSA infections in HIV+s.35 However, treatment with TMP-SMZ, commonly prescribed to prevent against opportunistic infections, appears to be protective in some HIV+ cohorts studied.17 Opportunistic infections are common in HIV+ individuals and antibiotics are often prescribed 35; thus, care should be taken when suspected MRSA infections arise. As with many pathogens and chronic antibiotic use, pressure may cause resistance to develop in the currently circulating strains of CAMRSA.35,46

Treatment with HAART has been suggested as being protective against MRSA infections in general. This is hypothesized to be due to fewer interactions with the health care system as well as shorter inpatient stays due to improved health while on HAART; thus, a potential point of MRSA exposure is avoided.47 Another retrospective case control study comparing HIV infected patients with or without CAMRSA infections also concluded that recent ART reduced the risk of colonization or infection.48


Colonization with SA is common, with approximately 30% of the general population estimated to have asymptomatic nasopharyngeal carriage at any time.1 The prevalence of colonization with SA and MRSA has been studied in various populations (hospital workers, drug abusers, patients with frequent medical interaction) and these rates are higher than the general population, contributing to spread within hospital communities. 1 The NHANES study examined USA300 colonization, and the data collected confirmed that CAMRSA can colonize the nares in individuals with no hospital contact.10

Ramsetty et al48 conducted a case-control study to examine risk factors for colonization or infection with MRSA specifically in HIV+s. HIV+ patients with USA 300 colonization or infection were compared to HIV+ patients harboring a non-USA300 strain. The only statistically significant risk factor specifically associated with the USA300 strain was a prior SSTI infection; however, if all MRSA colonizations/infections were examined as a whole, risk factors included a CD4+ count <200 and prior antibiotic use.48 ART was protective and, while not statistically significant, TMP-SMZ was trending toward significance as well, indicating a protective advantage. 48 (This data on the potential protective effect of TMP-SMZ is supported by another prospective cohort study which found 0/29 patients on TMX/SMP were colonized with MRSA.)49 The authors also note that 28/219 (22%) of all the MRSA isolates obtained from their HIV+ patients were CAMRSA, which is much higher than had been reported in earlier publications. 48 They hypothesize that, while the characterization of CAMRSA was not exactly the same in each study, this may be another confirmation of rising USA 300 infections in HIV+ patients. 48

But is colonization a true risk factor for infection in HIV+ individuals? While these patients may have higher rates of carriage, the link between carriage and subsequent infection, especially with specific MRSA strains, is not clear.19 A study by Ellis et al found that decontamination using mupirocin indeed eliminated carriage but did not impact the total number of subsequent MRSA infections. 50 Additionally, in HIV + MSMs with prior SSTIs, nasopharyngeal colonization was not associated with recurrence.37

However, it may be that colonization of other body sites is more predictive of subsequent CAMRSA infection. Perianal colonization increases infection risk in MSMs, and more frequently results in SSTIs of the buttocks and groin.15,34,39

In total, it appears that while carriage in the nares may be higher in HIV+ s, this may not make a carrier at increased risk of infection. It may however, result in spread of a clone in a limited population, in which there may be an increase risk of infection among those susceptible. This is supported by the trend toward significance in SSTI recurrence rates in MSM that have CAMRSA positive partners. 37

CAMRSA as a Presenting Illness for Initial HIV Diagnosis

Several case reports indicate that CAMRSA infections should now be considered as a potential presenting condition in patients who otherwise appear healthy but have undiagnosed HIV/AIDS. In one case study 29, a patient with a self-diagnosed "spider bite" was given an initial antibiotic regimen of clindamycin. Worsening of the "bite" resulted in the patient seeking additional medical treatment, at which time the diagnosis was necrotizing fasciitis (NF). The time from initial presentation to the diagnosis of NF was 2 weeks. Subsequent testing for HIV was positive, and the patients CD4+ and viral load tests indicated the patient had progressed to AIDS. The authors of the report conclude that CAMRSA needs to be considered as a potential pathogen for NF cases, even though S. aureus cases of NF are usually not common.29

Another case report by Sturgiss et a l 38 describes a case of penile cellulitis due to CAMRSA in a previously undiagnosed HIV+ individual. Open herpes simplex sores were the underlying reason for the initial seeking of treatment. The patient reported only heterosexual contacts and an HIV test performed in the past 3 years was negative. A panel of HIV, hepatitis, and STD tests were performed, and the HIV test came back positive, with a CD4+ count of 400 and a viral load of 210 copies/ml. Shortly after diagnosis, the patient developed severe swelling of the penis and lymphadenopathy that resulted in admission to hospital. Cultures of the resulting ulcerations revealed CAMRSA. Proper antibiotic therapy was started and the patient had a satisfactory response. The authors concluded that the CAMRSA infection may have been acquired by sexual contact via the initial herpetic lesion; however, because the patient's immune function was only mildly impacted, the HIV infection was probably not a factor in the virulence of the CAMRSA infection. 38

These reports are potential harbingers of ability of CAMRSA to manifest, perhaps more severely or with greater frequency, in HIV+s.


CAMRSA is an emerging pathogen not only in the general community but among HIV+ individuals. Additional epidemiological and treatment research is needed which considers the HIV positive population, and whether it is HIV status that increases risk of CAMRSA or behaviors and co-morbidities associated with HIV+s that are the risk factors, or both. Prospective studies are warranted. Awareness of clinicians of CAMRSA risk factors in HIV+s is needed to avoid additional morbidity and mortality in this group. Treatment with prior antibiotics for other opportunistic infections may be protective, but may also serve to increase antibiotic pressure and mutant selection. CAMRSA infections may be a presenting illness in patients that are unaware of their HIV+ status and have certain risk factors, thereby opening an opportunity for HIV testing.

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