Transcription: Simon Collins, HIV i-Base

Another talk in the IDU symposium was given by Frederick Altice from Yale University and looked at management of staphylococcal infections among IDUs. [1]

As an introduction, Professor Altice emphasied that skin and soft tissue infections are the leading cause for emergency room visits and hospitalisations for IDUs, with S aureus & S pyogenes the most common pathogens. [2] S aureus nasal carriage occurs in ~20% of people and associated with development of community- and nosocomial-acquired S aureus infections. [3, 4] IDUs have a higher rate of S aureus colonisation than the general population and is associated with subsequent infections in IDUs, [3, 4, 5]

An overview of risk factors and the relationship to HIV was summarised from a published paper form 2002. [6]

Skin and soft tissue infections (SSTIs) among IDUs include local (cellulitis & abscesses) and necrotising (complicated abscesses, necrotising fasciitis, pyomyositis, myonecrosis) infections. They are related to local tissue trauma as a direct effect of injecting drugs, tissue ischemia and inoculation of bacteria.

A recent study identified several potentially modifiable risk factors for SSTIs in injection drug users. The practice of injection directly into skin or muscle when veins are no longer accessible (“skin-popping”) is the strongest risk factor for abscess, followed by use of dirty needles and injection of a mixture of heroin and cocaine (“speedball”). The practice of drawing blood into the syringe before injection drug intravenously, known as “booting,” seems to be a risk factor in those who do not engage in skin-popping. The only protective factor identified was cleaning skin with alcohol before injection. Women may be at greater risk for SSTIs, presumably because they may have greater difficulty in accessing their veins.

The mechanism by which infection is established probably relates to tissue trauma, direct effect of drugs, tissue ischemia, and inoculation of bacteria. As a result of repeated injections into a single site, skin and surrounding tissue are damaged, develop local ischemia and necrosis, and become susceptible to infection. The drugs and diluents themselves may compound the tissue injury by causing vasospasm and thrombosis. Cocaine, in particular, has been associated with these complications.

Infecting organisms may come from the skin surface, contaminated needles, or saliva when the injection needle is licked or tablets are crushed between teeth before injection. Although one study suggested the drug itself might be the source of infecting bacteria, most other studies failed to establish this association. A recent outbreak of a clonal strain of group A streptococcus in Switzerland may have been caused by contaminated drug containers or by contaminated cocaine, but investigators were unable to prove that either was definitely the source.

Infection with HIV has been recognised as a risk factor by some but not all investigators. Immune disorders may contribute to injection drug users’ predisposition to infection. Recent evidence for the expression of opiate receptors on immune cells, specifically receptors for morphine and the metabolites of heroin, support a connection between opiates and immune function. Opiates suppress several T-cell functions important for cell-mediated immunity and also inhibit phagocytosis, chemotaxis, and killing by polymorphonuclear neutrophil leukocytes (PMNs) and macrophages in humans. This impairment of phagocytosis and killing may be an important additional cause for the frequency with which injection drug users present with SSTIs caused by common bacterial pathogens.

Invasive infections among IDUs (most commonly is S aureus > Strep > GNRs) usually include bacteremia from local source (lungs, SSTIs), endocarditis and osteomyelitis. Endocarditis more likely to be right-sided among IDUs than among non-IDUs and duration of antibiotics is prolonged though shorter duration may be possible for right-sided infections.

MRSA has increased significantly in North America, accounting for 0ver 40% of ICU infection. When hospital-acquired (h-MRSA) it is plasmid-mediated, not associated with toxin production, associated with recent hospitalisation and use of antibiotics and highly resistant to most oral antibiotics, except linezolid. By contrast, when community-acquired (c-MRSA) it is chromosomally-mediated, associated with toxin production (Panton-Valentine leukocidin) and person-to-person transmission that is not associated with traditional risk factors [IDUs, sexual contact and crowding - ie athletes, prisoners, homeless shelters, day care centers). It also remains sensitive to many oral antibiotics (TMP/SMZ, tetracycline, etc).

Staphylococcal colonisation among IDUs is also increasing. A survey in 2000 to detect methicillin-resistant Staphylococcus aureus (MRSA) colonisation in Vancouver downtown east side injection drug users (IDUs) revealed an MRSA nasal colonisation incidence of 7.4%. This is a follow-up study to determine the current prevalence of MRSA colonisation and to further characterise the isolates and risk factors for colonisation. S. aureus was isolated from 119 of 301 (39.5%) samples; three (2.5%) participants had both methicillin-sensitive S. aureus (MSSA) and MRSA, resulting in 122 isolates. Of these, 54.1% were MSSA and 45.9% were MRSA, with an overall MRSA rate of 18.6%. USA-300 (CMRSA-10) accounted for 75% of all MRSA isolates; 25% were USA-500 (CMRSA-5). The antibiograms of USA-300 compared to USA-500 isolates showed 100% versus 7.1% susceptibility to tri- methoprim-sulfamethoxazole (TMP-SMX) and 54.8% versus 7.1% susceptibility to clindamycin. MRSA nasal colonisation in this population has increased significantly within the last 6 years, with USA-300 replacing the previous strain. Most of these strains are PVL positive, and all were susceptible to TMP-SMX.

In a 2001 analysis of a methadone (MM) and heroin (HM) maintenance programme in Basel, nasal carriage higher in MM (43%) than in HM (23%) patients. There was difference in recent or remote hospitalisation, MM subjects were more likely to have used antibiotics in previous month (12% vs 4%), to be HIV-positive (20% vs 6%) and have no IDU (34% vs 0%). In multivariate analysis, enrolled in MM was the only significant (AOR 2.27) correlate of S aureus colonization. No MRSA was isolated but subsequent studies have demonstrated MRSA transmission between drug users and introduction of new MRSA strains. [6]

A recent (2008) case-controlled study of 60 hospitalised opioid dependent (OD) and 60 non-drug users in Egypt, reported that colonization was higher in drug vs. non-drug users (30% vs 10%), an increased risk associated with duration of drug use and use of non-prescription antibiotics and that 58% of active MRSA infections associated with colonisation. [7]

MRSA colonisation persists for years, despite treatment of infection. contact precautions and isolation of wounds are recommended but universal screening, isolation and eradication of the carrier state remain controversial.

In summary, the following five points were outlined.

• IDUs exist on all continents and are more likely to be colonised with S aureus.
• Morbidity and mortality related to S Aureus infections is greater among IDUs.
• Colonisation with S aureus, including MRSA, is associated with increased risk for infection.
• Infection can be reduced with skin cleaning and sterile syringes.
• MRSA prevalence is variable but growing in different regions of the world, thus requiring increased surveillance to guide clinical practice.

References
This presentation was part of a symposium on issues important to a global response relating to injecting drug use: Injecting Drug Use and Infectious Diseases: Implications for the Global HIV/AIDS Response (An IAS/IDSA Partnership). Symposium TUSY06.
http://www.aids2008.org/Pag/PSession.aspx?s=18

1. Frederick Altice. Staph infections in intravenous drug users. Abstract TUSY0603.
2. Palepu A et al. Hospital utilization and costs in a cohort of injection drug users. CMAJ August 21, 2001; 165 (4).
http://www.cmaj.ca/cgi/content/abstract/165/4/415
3. Kluytmans J et al. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev. 1997;10:505-20. [PMID: 9227864]
4. von Eiff C et al, Nasal Carriage as a Source of Staphylococcus aureus Bacteremia. NEJM 2001 Volume 344:11-16. (4 January 2001).
http://content.nejm.org/cgi/content/abstract/344/1/11?ck=nck
5. Bassetti et al. Staphylococcus aureus infections in injection drug users: risk factors and prevention strategies. Infection 2004 Jun;32(3):163-9.
http://www.ncbi.nlm.nih.gov/pubmed/15188077
6. Fleisch F et al. Transregional spread of a single clone of methicillin–resistant Staphylococcus aureus between groups of drug users in Switzerland. Infection, 2005.
http://www.springerlink.com/content/n8205g8169770204/
7. El-Sharif A, Ashour HM. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) colonization and infection in intravenous and inhalational opiate drug abusers. Exp Biol Med, 2008 Jul;233(7):874-80.
http://www.ncbi.nlm.nih.gov/pubmed/18445771