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Microbiology !!navigator!!

Staphylococci are gram-positive cocci that form grapelike clusters on Gram's stain; they are catalase positive (unlike streptococci), nonmotile, aerobic, and facultatively anaerobic. Staphylococcus aureus, which is distinguished from other staphylococci by its production of coagulase, is the most virulent species.

S. Aureus Infections !!navigator!!

Epidemiology !!navigator!!

S. aureus is an important cause of community-acquired infections and a leading cause of nosocomial infections.

  • S. aureus is a component of the normal human flora, most frequently colonizing the anterior nares and oropharynx but also colonizing the skin (particularly damaged skin), vagina, axilla, and perineum. These sites of colonization are reservoirs for future infection.
  • Of healthy persons, 20-40% are transiently colonized with S. aureus, while ∼10% are persistently colonized. The rate is elevated among insulin-dependent diabetic pts, HIV-infected persons, injection drug users, hemodialysis pts, and pts with skin damage.
  • Transmission of S. aureus most frequently results from direct personal contact, although spread via respiratory secretions has been reported. Most S. aureus infections are caused by a strain that is already a component of the pt's own microbiota.
  • Methicillin-resistantS. aureus (MRSA) is common in hospitals, and its prevalence is increasing dramatically in community settings among individuals without prior medical exposure.
    • In the United States, strain USA300 (defined by pulsed-field gel electrophoresis) causes most community-acquired MRSA (CA-MRSA) infections and can cause severe disease in immunocompetent pts.

Pathogenesis !!navigator!!

S. aureus is a pyogenic pathogen known for its capacity to induce abscess formation.

  • Invasive disease: For invasive S. aureus infection to occur, some or all of the following steps are necessary:
    • - Colonization/inoculation: Bacteria colonize tissue surfaces, particularly the anterior nares, or are inoculated directly into tissue-e.g., as a result of minor abrasions or via IV access catheters.
    • - Invasion: Bacteria replicate at the site of infection and elaborate enzymes that facilitate survival and local spread. CA-MRSA isolates that produce the Panton-Valentine leukocidin toxin have been linked to more serious infections.
    • - Evasion of host defense mechanisms: S. aureus possesses an antiphagocytic polysaccharide microcapsule that facilitates evasion of host defenses and plays a role in abscess formation. Organisms can survive intracellularly and then cause recrudescent infections when conditions are suitable.
    • - Metastatic spread: S. aureus can survive in PMNs and may use these cells to spread to and seed other tissue sites.
  • Toxin-mediated disease: S. aureus produces three types of toxin: cytotoxins, pyrogenic toxin superantigens, and exfoliative toxins.
    • Antitoxin antibodies are protective against toxin-mediated staphylococcal illness.
    • Enterotoxins and toxic shock syndrome toxin 1 (TSST-1) act as “superantigens” or T-cell mitogens and cause the release of large amounts of inflammatory mediators, producing multisystem disease that includes fever, rash, and hypotension.

Diagnosis !!navigator!!

S. aureus infections are readily diagnosed by Gram's stain and microscopic examination of infected tissue.

  • Routine cultures of infected material usually yield positive results, and blood cultures are sometimes positive even when infections are localized to extravascular sites.
  • PCR assays have been developed for rapid testing and are increasingly being used.

Clinical Syndromes !!navigator!!

SKIN AND SOFT TISSUE INFECTIONS- S. aureus causes a variety of cutaneous infections characterized by pus-containing blisters, many of which can also be caused by group A streptococci and other streptococcal species. Predisposing factors include skin disease (e.g., eczema), skin damage (e.g., minor trauma), injections, and poor personal hygiene.
  • Infections can be superficial (e.g., folliculitis, cellulitis, impetigo) or deep and painful (e.g., furuncles, carbuncles, hidradenitis suppurativa).
    • Carbuncles (often located in the lower neck) are more severe and painful than furuncles (boils that extend from hair follicles) and are due to coalesced lesions extending to deeper SC tissue.
    • Mastitis in lactating women can range from superficial cellulitis to abscess.
MUSCULOSKELETAL INFECTIONS- See Chap. 87 Infections of the Skin, Soft Tissues, Joints, and Bones for additional details.
  • S. aureus is among the most common causes of osteomyelitis arising from either hematogenous dissemination or contiguous spread from a soft tissue site (e.g., diabetic or vascular ulcers).
    • Hematogenous osteomyelitis in adults is often vertebral and occurs in pts with endocarditis, pts undergoing hemodialysis, injection drug users, or diabetics. Intense back pain and fever can occur, but infections may also be clinically occult.
    • - Epidural abscess is a serious complication that can present as trouble voiding or walking or as radicular pain in addition to symptoms of osteomyelitis; neurologic compromise can develop in the absence of timely treatment, which often requires surgical intervention.
    • Osteomyelitis from contiguous soft-tissue infections is suggested by exposure of bone, a draining fistulous tract, failure to heal, or continued drainage.
  • S. aureus is the most common cause of septic arthritis in native joints of both adults and children. S. aureus septic arthritis in adults may result from trauma, surgery, or hematogenous dissemination.
    • The joints most commonly affected are the knees, shoulders, hips, and phalanges.
    • Examination of synovial fluid reveals >50,000 PMNs/µL and gram-positive cocci in clusters on Gram's stain.
  • Pyomyositis, an infection of skeletal muscles that is seen in tropical climates and in immunocompromised pts (e.g., HIV-infected pts), causes fever, swelling, and pain overlying involved muscle and is usually due to S. aureus.
RESPIRATORY TRACT INFECTIONS-
  • Newborns and infants can develop serious infections characterized by fever, dyspnea, and respiratory failure; pneumatoceles (shaggy, thin-walled cavities), pneumothorax, and empyema are known complications.
  • Community-acquired pneumonia usually follows viral infections (e.g., influenza) and manifests as fever, bloody sputum production, and midlung-field pneumatoceles or multiple patchy pulmonary infiltrates.
    • Blood cultures are usually negative.
  • Nosocomial pneumonia is common in intubated pts and is indistinguishable from pneumonia of other bacterial etiologies.
    • Pts produce an increased volume of purulent sputum and develop fever, new pulmonary infiltrates, and respiratory distress.
BACTEREMIA AND SEPSIS- The incidence of metastatic seeding during bacteremia has been estimated to be as high as 31%, with bones, joints, kidneys, and lungs most commonly infected.
  • Diabetes, HIV infection, and renal insufficiency are often seen in association with S. aureus bacteremia and increase the risk of complications.
INFECTIVE ENDOCARDITIS- See Chap. 83 Infective Endocarditis for additional details.
  • S. aureus is the leading cause of endocarditis worldwide and accounts for 25-35% of cases.
  • The incidence is increasing as a result of injection drug use, hemodialysis, intravascular prosthetic devices, and immunosuppression.
  • Mortality rates range from 20% to 40% despite the availability of effective antibiotics.
  • The four clinical settings in which S. aureus endocarditis is encountered are (1) right-sided endocarditis in association with injection drug use, (2) left-sided native-valve endocarditis, (3) prosthetic-valve endocarditis, and (4) nosocomial endocarditis.
URINARY TRACT INFECTIONS- UTIs due to S. aureus are uncommon and suggest hematogenous dissemination.
PROSTHETIC DEVICE-RELATED INFECTIONS- Compared with coagulase-negative staphylococci (CoNS), S. aureus causes more acute disease, with localized and systemic manifestations that tend to be rapidly progressive. Successful treatment usually involves removal of the prosthetic device.
CA-MRSA INFECTIONS- While the skin and soft tissues are the most common sites of infection associated with CA-MRSA, 5-10% of these infections are invasive and potentially life threatening (e.g., necrotizing fasciitis, necrotic pneumonia, sepsis, purpura fulminans).
TOXIN-MEDIATED DISEASE- Each class of toxin produced by S. aureus results in a characteristic syndrome.
  • Food poisoning: results from inoculation of toxin-producing S. aureus into food by colonized food handlers, with subsequent toxin elaboration in growth-promoting foods (e.g., custard, potato salad, processed meat)
    • The heat-stable toxin is not destroyed even if heating kills the bacteria.
    • Because the disease is caused by preformed toxins, its onset is rapid and explosive, occurring within 1-6 h of ingestion of contaminated food.
    • The chief signs and symptoms are nausea and vomiting, but diarrhea, hypotension, and dehydration may occur. Fever is absent.
    • Symptoms resolve within 8-10 h; treatment is entirely supportive.
  • Toxic shock syndrome (TSS): results from elaboration of an enterotoxin (many nonmenstrual TSS cases) or TSST-1 (some nonmenstrual cases and >90% of menstrual cases)
    • Although the specific toxin may differ, the clinical presentation is similar in menstrual and nonmenstrual cases.
    • Diagnosis is based on a constellation of clinical findings. Table 89-1 Case Definition of Staphylococcus aureus Toxic Shock Syndrome summarizes the case definition for staphylococcal TSS.
    • Menstrual cases occur 2-3 days after menses begin.
    • Illness occurs only in people who lack antibody to the toxin.
  • Staphylococcal scalded-skin syndrome (SSSS): most often affects newborns and children. Fragility of the skin, with tender, thick-walled, fluid-filled bullae, can lead to exfoliation of most of the skin surface. Nikolsky's sign is positive when gentle pressure on bullae causes rupture of lesions and leaves denuded underlying skin.

Prevention !!navigator!!

Hand washing and careful attention to appropriate isolation procedures prevent the spread of S. aureus infection. Elimination of nasal carriage (e.g., with mupirocin) and/or colonization of additional body sites (e.g., with chlorhexidine) with S. aureus has been successful in high-risk pts (e.g., those in intensive care units).

Infections Caused By Coagulase-Negative Staphylococci !!navigator!!

Microbiology !!navigator!!

CoNS are generally less virulent than S. aureus but are important and common causes of prosthetic-device infections.

  • Of CoNS species, S. epidermidis most often causes disease. This organism is a normal component of the skin, oropharyngeal, and vaginal flora.
  • S. saprophyticus is a common cause of UTIs.
  • S. lugdunensis and S. schleiferi are more virulent than other CoNS species and cause serious infections, possibly because they apparently share more virulence determinants with S. aureus than do other CoNS species.

Pathogenesis !!navigator!!

CoNS are uniquely adapted to cause prosthetic-device infections because they can elaborate an extracellular polysaccharide (glycocalyx or slime) that forms a biofilm on the device surface, protecting bacteria from host defenses as well as from antibiotic treatment while allowing bacterial survival.

Clinical Syndromes !!navigator!!

CoNS cause diverse prosthetic device-related infections. Signs of localized infection are usually subtle, disease progression is slow, and systemic findings are limited. Fever and mild leukocytosis may be documented. Infections not associated with prosthetic devices are infrequent, but up to 5% of native-valve endocarditis cases have been due to CoNS in some series. Neutropenic pts and preterm infants are also at risk of CoNS infection, particularly those pts with intravascular devices.

Diagnosis !!navigator!!

CoNS are readily detected by standard methods, but distinguishing infection from colonization is often problematic because CoNS are common contaminants of cultures of blood and other sites. Only 10-20% of blood cultures positive for CoNS reflect true bacteremia.

TREATMENT

Staphylococcal Infections

  • Source control (e.g., drainage of suppurative collections, removal of infected prosthetic devices) and rapid institution of antibiotics are essential. The emergence of CA-MRSA has increased the importance of culturing material from all collections to identify the pathogen and determine its antimicrobial susceptibility.
  • Antibiotic therapy for S. aureus infection is generally prolonged (i.e., 4-6 weeks) for complicated infections, defined as those in which blood cultures remain positive 96 h after initiation of therapy, the infection was acquired in the community, a removable focus of infection is not removed, or the infection is deep-seated. For uncomplicated bacteremias in which shorter therapy (i.e., 2 weeks) is planned, a transesophageal echocardiogram to rule out endocarditis is warranted.
  • Antimicrobial therapy for serious staphylococcal infections is summarized in Table 89-2 Antimicrobial Therapy for Staphylococcal Infectionsa .
    • Penicillinase-resistant β-lactams, such as nafcillin, oxacillin, and cephalosporins, are highly effective against penicillin-resistant strains.
    • The incidence of MRSA is high in hospital settings, and strains intermediately or fully resistant to vancomycin have been described. In general, vancomycin is less reliably bactericidal than the β-lactams and should be used only when absolutely indicated. Desensitization to β-lactams remains an option for life-threatening infections.
    • Among newer antistaphylococcal agents, ceftaroline is a fifth-generation cephalosporin with bactericidal activity against MRSA; daptomycin is bactericidal but is not effective in pulmonary infections; quinupristin/dalfopristin is typically bactericidal but is only bacteriostatic against isolates resistant to erythromycin or clindamycin; linezolid is bacteriostatic and offers similar bioavailability after oral or parenteral administration; and tigecycline, a broad-spectrum minocycline analogue, is bacteriostatic against MRSA. Telavancin-a lipoglycopeptide derivative of vancomycin-is active against strains with reduced susceptibility to vancomycin (i.e., vancomycin-intermediate S. aureus, or VISA), and the long-acting lipoglycopeptides (dalbavancin and oritavancin) can be administered weekly.
  • Other alternatives include the quinolones, but resistance to these drugs is increasing, especially among MRSA strains.
  • Trimethoprim-sulfamethoxazole (TMP-SMX) and minocycline have been used successfully to treat MRSA infections in cases of vancomycin toxicity or intolerance.
  • Combinations of antistaphylococcal agents have been used to enhance bactericidal activity, to optimize empirical therapy (e.g., using a β-lactam plus vancomycin), and, in selected instances (e.g., right-sided endocarditis), to shorten the duration of therapy.

Special considerations for treatment include:

  • Empirical therapy: Empirical coverage for MRSA is generally indicated.
  • Salvage therapy: The optimal regimen for treatment of persistent bacteremia (>3 days) despite appropriate therapy is not known, although a combination of different antibiotic classes is often suggested.
  • Uncomplicated skin and soft tissue infections: Incision and drainage, with or without oral antibiotics, is usually adequate.
  • Native-valve endocarditis: A β-lactam is recommended for methicillin-sensitive S. aureus, and vancomycin (15-20 mg/kg q8-12h) or daptomycin (6-10 mg/kg q24h) is recommended for MRSA. Treatment should continue for 6 weeks.
  • Prosthetic-valve endocarditis: Surgery is often needed in addition to antibiotics. The combination of a β-lactam drug (or either vancomycin or daptomycin if MRSA is involved) with gentamicin for 2 weeks and rifampin for ≥6 weeks is indicated.
  • Hematogenous osteomyelitis or septic arthritis: A 4-week treatment course is adequate for children, but adults require longer courses. Joint infections require repeated aspiration or arthroscopy to prevent damage from inflammatory cells.
  • Chronic osteomyelitis: Surgical debridement-in addition to antibiotic therapy-is needed in most cases.
  • Prosthetic-joint infections:Ciprofloxacin and rifampin have been used successfully in combination, particularly when the prosthesis cannot be removed.
  • TSS: Supportive therapy and removal of tampons or other packing material or debridement of an infected site are most important. A combination of clindamycin and a semisynthetic penicillin (or vancomycin if the isolate is resistant to methicillin) is often recommended.
    • Clindamycin is recommended because it is a protein synthesis inhibitor and has been shown to decrease toxin synthesis in vitro; linezolid also appears to be effective.
    • Anecdotally, IV immunoglobulin is helpful.

Outline ⬆

Section 7. Infectious Diseases