Pathogens>Bacteria>

MICROBIOLOGY

• Staphylococci (Staph): clustered gram-positive beta-hemolytic bacteria. S. aureus (SA) is coagulase positive.
• Coagulase-negative Staph (CoNS): >30 species, 15 of which are human pathogens. S. epidermidis, S. saprophyticus (novobiocin resistant), S. haemolyticus, S. lugdunensis, & S. schleiferi are most commonly isolated.
• SA produces several toxins, including enterotoxins, epidermolytic toxins, & toxic shock syndrome toxins (TSST)
• Staph grow rapidly on blood agar and other non-selective media. They can survive harsh environmental conditions, high salt media, & are relatively heat-resistant.
• Methicillin resistance: >80% of CoNS, and an increasing number of both hospital acquired & community acquired SA (MRSA) encompasses all B-lactam antibiotics, including cephalosporins. Vancomycin-intermediate resistance (VISA) and vancomycin-resistant strains have emerged.

CLINICAL

• Both MRSA and methicillin-sensitive SA (MSSA) infections occur more frequently in HIV-infected pts. Advanced immunosuppression increases the risk.
• Increased prevalence of IDU among HIV-infected pts, frequent hospitalization, frequent use of antimicrobials, & need for long-term venous access have further increased risk of SA infections, especially MRSA.
• Signs and Sx depend on degree of immunosuppression & site of infection (see below).
• Dx: SA and CoNS grow easily in Cx; blood, urine, CSF, sputum, skin, & bone Cx, as indicated, should be obtained. Further investigation depends on site of infection.
• Community acquired (CA-) MRSA strains now account for >75% of soft tissue infections.
• CA-MRSA vs. hospital acquired MRSA: (1) more susceptible to ABx other than beta-lactams; (2) genotypes are not the same as isolates from local hospitals; (3) mainly harbor different meticillin-resistance cassettes; (4) CA-MRSA isolates more likely to encode a putative virulence factor called Panton-Valentine leukocidin.
• Currently, one strain of CA-MRSA predominates (staphylococcal chromosomal cassette type IV, sequence type 8, Panton-Valentine leukocidin gene positive)

SITES OF INFECTION

• Skin & soft tissue: cellulitis, folliculitis (SA), furuncles & carbuncles (SA), impetigo (SA), post-operative wound infections.
• Musculoskeletal: pyomyositis (SA), abscesses (mostly SA), osteomyelitis, septic arthritis, prosthetic joint infections.
• Cardiovascular: bacteremia, endocarditis, pericarditis (SA).
• Pulmonary: necrotizing pneumonia (SA), empeyema (SA)
• Neurological: abscesses, meningitis (mostly SA), & shunt infections (both SA and CoNS)
• GI: epidemic acute food poisoning (SA)
• Systemic: toxic shock syndrome.
• Urinary tract: isolation of SA from urine should prompt immediate evaluation for an endovascular source

TREATMENT

• Penicillin usually not effective to treat SA or CoNS infections due to widespread resistance.
• >80% of CoNS & a growing number of hospital-acquired & community acquired SA are methicillin-resistant.
• Vancomycin should not be used to treat MSSA as a convenience; efficacy inferior to beta-lactams.
• Short courses of parenteral therapy (2 wks) for endovascular infections should be discouraged in HIV-infected pts.
• CA-MRSA may be sensitive to >1of following: clindamycin, TMP-SMX, fluoroquinolones, or macrolides. Once resistance profile known, they may be used for non-life threatening infections (usually skin, soft tissue, & bone infections).
• Regimen and duration depends on site of infection and sensitivity of organisms; in general skin, soft tissue infections, & uncomplicated pulmonary infections require 10-14 d of Rx, endovascular & bone infections at least 4-6 wks of therapy.
• When infected collections of fluid are found (empyema, abscesses), surgical drainage must accompany antimicrobials Rx.
• Any indwelling vascular lines should be removed; success of eradicating endovascular staph infections (especially SA) without foreign body removal is low (<30%)
• Isolation of SA from blood requires therapy. Unlike CoNS, SA should not be viewed as a contaminant.

• MRSA decolonization has not led to reduction in infection in all pt populations; effect of any decolonization strategy seems to last only about 90 days
• Mupirocin: eradication of nasal colonization after initial (5-7 days) use is 88% for HIV + pts, but resistance develops quickly
• Chlorhexidine baths used in combination with intranasal mupirocin in uncontrolled trials and during outbreaks

• PO: cephalexin (500 mg PO qid), dicloxacillin (500 mg PO qid), clindamycin (300 mg PO qid), fluoroquinolones (advanced generation FQ tend to have better gram + coverage, e.g. levofloxacin, gatifloxacin, moxifloxacin), TMP-SMX, & minocycline
• IV: antistaphylococcal PCN [nafcillin (1-2 gm IV q 4h) or oxacillin (1-2 gm IV q4h)]; if MRSA, vancomycin (15 mg/kg IV q12h); linezolid (600 mg IV q12h).
• Synergy: gentamicin 1 mg/kg IV q8h; rifampin 300 mg IV/PO q12h. Limit to first 5 days of Rx. No benefit has been shown in extending the course.
• Endocarditis: MSSA-nafcillin or oxacillin +/- gentamicin or rifampin; MRSA-vancomycin +/- gentamicin or rifampin x 4-6 wks. Short courses for R-sided endocarditis not recommended in HIV-infected pts; new data for daptomycin (6mg/kg IV q24h) (see Fowler VG, Boucher HW, Corey GR, et al.) in MSSA and MRSA endocarditis.
• CoNS: Vancomycin +/- rifampin; occasionally may be sensitive to FQ or TMP-SMX; tigecycline, linezolid, and daptomycin are alternate choices.
• Intermediate resistance and full resistance to vancomycin in SA has been reported. Case reports suggest that the use of linezolid in combination with rifampin may be successful
• Susceptibility to fluoroquinolones, aminoglycosides, clindamycin, TMP-SMX, & rifampin must be ascertained prior to the use of these agents.

Drug Comments

FOLLOW UP

• Adjust ABx doses based or renal and hepatic function. Re-dose vancomycin when trough level <10-15; in general, no need to measure peak/trough levels of aminoglycosides when used at synergistic doses.
• Incomplete Rx may lead to hematogenous dissemination of SA and complications days to years after discontinuation of Rx.
• Resistance to erythromycin in CA-MRSA may suggest inducible resistance to clindamycin; ensure that a D-test is performed before clindamycin is prescribed.

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Flucloxacillin