Staphylococcus Infections

Beverly L. Connelly

Staphylococci are ubiquitous inhabitants of the skin and mucous membranes of humans and other mammals. They exist in a commensal relationship until a breach in a cutaneous or mucosal barrier permits staphylococcal access to deeper tissues and the bloodstream or until a foreign body or medical device provides a foothold. The production of coagulase, an enzyme that clots plasma, distinguishes Staphylococcus aureus from other medically important staphylococci. Those that do not produce coagulase are grouped collectively as coagulase-negative staphylococci (CoNS) and represent the most common resident bacteria of humans.¹

COAGULASE-NEGATIVE STAPHYLOCOCCI

EPIDEMIOLOGY

Coagulase-negative staphylococci (CoNS) colonize virtually all normal skin. Because of the commensal nature of the CoNS, they are often recovered from specimens from superficial sites and may be recovered from body fluids and deep sites when inadequate or improper collection techniques have been employed. Recovery of CoNS from a normally sterile body site must be interpreted in light of the clinical circumstances of the patient. Of the more than 30 species, at least 15 are indigenous to humans, with S epidermidis being the most common of the resident CoNS.

Staphylococcus hominis and S saccharolyticus are common resident flora as well, with S haemolyticus and S warneri less frequent. Other transient colonizers include S xylosus, S simulans, S cohin, and S lugdunensis. Selected species are also recognized for the special niches they colonize, including S capitus (scalp), S auricularis (ear), and S saprophyticus (genitourinary tract).^2,3S lugdunensis has been recognized for its propensity to cause severe infections of skin and soft tissue in the absence of underlying risk factors.⁵ In one series, isolates were associated particularly with abscesses in the perineal and gluteal areas.^7,8S lugdunensis endocarditis has a predilection for native valves and may result in a fulminant course similar to that of S aureus.^9-12 Identification in the laboratory may be difficult because S lugdunensis may produce clumping factor, a heat-stable DNAse easily misidentified as coagulase on initial slide screening tests for S aureus.^1,13

PATHOPHYSIOLOGY AND GENETICS

Most infections attributed to coagulase-negative staphylococci (CoNS) are facilitated by the formation of biofilm on host tissue or medical device surfaces. Binding to indwelling devices appears to be mediated in part by a fibronectin-binding protein as well as surface proteins SSP-1 and SSP-2, an autolysin, a biofilm-associated protein, and capsular polysaccharide/adhesin (PS/A). In addition, polysaccharide intracellular adhesin (PIA) facilitates accumulation of S epidermidis in multilayered cell clusters, and associates with additional extracellular proteins resulting in biofilm formation.^14-16 Biofilms are key to the pathogenesis of foreign body–associated infections, offering the bacteria resistance to antimicrobial therapy as well as a means of evading the host immune responses. S saprophyticus is uniquely outfitted as a genitourinary pathogen because of a novel cell wall–anchored protein involved in adherence to uroepithelial cells,¹⁷ redundant urine adaptive transporter systems, and urease.¹⁸

CLINICAL MANIFESTATIONS

Device-Related Infections

Coagulase-negative staphylococci (CoNS) are the leading causes of medical device–related infections that can be attributed to colonization and subsequent biofilm production. Staphylococcus S epidermidis has been associated with approximately 34% of catheter-associated bloodstream infections and approximately 40% of the cases of bacterial peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).^20,21 Hemodialysis catheters and ventriculoperitoneal shunt catheters frequently fall victim to CoNS and to S epidermidis in particular.^22-24S lugdunensis may be an emerging cause of a variety of these infections.¹³ The biologic characteristics of these organisms and their ability to escape immune surveillance facilitate prolonged smoldering shunt infections that may manifest only as intermittent device malfunctions. As many as one half of patients present without overt signs of central nervous system inflammation; thus, a high index of suspicion is required to make the appropriate diagnosis.

Bacteremias

Determining whether a positive blood culture for coagulase-negative staphylococci (CoNS) in the presence of a catheter equates with disease can be problematic when only a single blood culture is obtained. CoNS have been responsible for approximately one third of the bacteremias in children receiving chemotherapy for childhood malignancies, patients receiving hemodialysis, and a majority of bacteremias reported in infants in neonatal intensive care units.^25-27 CoNS are more recently recognized as causes of native-valve endocarditis in normal as well as compromised hosts.²⁸ CoNS are the most common cause of bacteremia following pediatric lung transplant.²⁹ To the extent that the skin is the primary source for CoNS, these trends may change as quality improvement initiatives focused efforts on preventing infections related to line insertion and line care. To the extent that mucosal colonization serves as the portal of entry for bacteremia, CoNS bacteremias will continue to plague intravascular catheter use.³⁰ In neonates, CoNS may be associated with cellulitis and abscesses, omphalitis, pneumonia, and possibly with necrotizing enterocolitis. Risks for infection include the presence of intravascular devices, loss of integrity of skin or mucosal barriers, parenteral nutrition (specifically intravenous lipid), and use of immunosuppressive drugs. Additional information on catheter-associated infections can be found in Chapter 239.

Urinary Tract Infections

Staphylococcus saprophyticus is the second most common cause of uncomplicated urinary tract infections (UTIs) in adolescent females and young women, although it is the cause in only 0.3% to 3% of UTIs in all ages.^31-33 Asymptomatic carriage of S saprophyticus may occur in a small number of healthy women; however, S saprophyticus is generally detected in the presence of a symptomatic urinary tract infection that may involve the upper tract. Urethral trauma associated with intercourse is speculated to be a significant risk factor preceding infection in some cases.³⁴ Diagnosis requires recognition that colony counts may be falsely low (< 10⁵ cfu/mL).³⁵ Other coagulase-negative staphylococci (CoNS) may be implicated in catheter-associated urinary tract infections and should prompt catheter removal.

TREATMENT

Virtually all S epidermidis produce β-lactamase and more than 80% of S epidermidis are methicillin resistant.² Until speciation and formal susceptibility testing is available, vancomycin is the drug of choice for coagulase-negative staphylococci (CoNS) infections.³⁶ Central nervous system/shunt infections require higher dosing of vancomycin to achieve adequate concentrations in the cerebrospinal fluid. The addition of gentamicin or rifampin to vancomycin should be considered for severe infections. Nearly all CoNS will be susceptible to linezolid, and about half will be susceptible to clindamycin, trimethoprim/sulfamethoxazole, and gentamicin; fewer will be susceptible to macrolides.³⁶ Unlike other CoNS, S lugdunensis generally demonstrates low minimum inhibitory concentrations for penicillins and cephalosporins¹² and only about 20% are β-lactamase positive.⁸ Since β-lactams generally exhibit superior efficacy when compared to vancomycin, use of a penicillin or a cephalosporin would be preferred to treat S lugdunensis if it is β-lactamase negative. Staphylococcus saprophyticus is generally susceptible to ampicillin, cephalosporins, trimethoprim/sulfamethoxazole, and ciprofloxacin, among others drugs commonly used to treat urinary tract infections.³⁷

STAPHYLOCOCCUS AUREUS

EPIDEMIOLOGY

Humans and other mammals are the natural reservoirs for Staphylococcus aureus. In humans, the principal site for S aureus colonization is the nares, although the pharynx, axillae, vagina, and damaged skin are also important reservoirs. Nasal carriage with S aureus may be 50% to 85% in selected high-risk populations. Nasal carriage may be persistent (∼20%), intermittent (∼60%), or absent (∼20%).³⁸ Individuals who are intermittently colonized may be recolonized with the same strain or different strains. Carriage is an important risk factor for the development of infection in patients undergoing selected surgeries, hemodialysis, or peritoneal dialysis, as well as those with indwelling catheters, underlying conditions such as diabetes, immune deficiencies, or intravenous drug use.^39,40

The severity and extent of invasion by S aureus are dependent on the complex interplay between host defenses and virulence factors of the bacteria. Infections may be mild and self-limited or severe and life threatening, especially in individuals with underlying risk factors. Staphylococcus aureus is also responsible for an array of toxin-mediated diseases that may also be mild or potentially life threatening, as in toxic shock syndrome in otherwise healthy individuals.

Methicillin-resistant S aureus (MRSA) emerged as a cause of serious health care–associated infections in the 1970s and by 2003 accounted for 64% of the S aureus isolates in US intensive care units.⁴¹ During the recent decade, community-associated MRSA (CA-MRSA) has emerged as a cause of severe infections in individuals without underlying risk factors.⁴² The clinical features of cases and the microbiologic characteristics of the strains indicated that these were distinctly different from health care–acquired MRSA strains. Outbreaks of CAMRSA skin and soft tissue infections have been reported in childcare centers⁴³; high school,⁴⁴ college,⁴⁵ and professional sports teams⁴⁶; and military recruits.^47-49 The estimated prevalence of nasal colonization with CA-MRSA is 1.5% to 3%,^49,50 much less than that of MSSA; however, in a prospective observational study of military recruits, individuals colonized with CA-MRSA were 10 times more likely to experience an infection than those colonized with MSSA.⁴⁹ As expected for any community bacteria, these CAMRSA strains are being seen in health care settings now as well.⁵¹

PATHOPHYSIOLOGY

Staphylococcal colonization and infections begin with bacterial adherence to host tissues. Surface and secreted molecules of S aureus are present in various combinations among staphylococcal populations.⁵² Microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) are the family of cell wall–anchored staphylococcal adhesins.⁵³ These proteins bind staphylococci variously to extracellular matrix composed of collagen, fibronectin, fibrinogen, bone sialoprotein, elastin, or laminin.^54-56 The distribution of MSCRAMM genes among clinical isolates of S aureus suggests participation of these proteins in selected diseases. For example, in a study of the distribution of MSCRAMM genes among clinical isolates of S aureus, detection of the gene for bone sialoprotein-binding protein (bbp) was associated more with osteomyelitis/arthritis than with endocarditis, while detection of the gene for fibronectin-binding protein B (fnbB) was associated more with endocarditis, although the associations were not absolute.⁵⁵

Additional surface molecules, as well as secreted proteins of staphylococci, interfere with host defenses. About 60% of S aureus secrete a chemotaxis inhibitor protein (CHIPS) that functions in concert with the extracellular adherence protein (Eap) to inhibit neutrophil recruitment to the site of infection.⁵³ The secreted hemolysins (α, β, σ, γ) and Panton-Valentine leukocidin (PVL) are cytotoxic to either red cells and white cells or white cells alone (PVL). There is a strong association between PVL expression and recurrent skin and soft tissue infections as well as severe necrotizing deep tissue infections.⁶⁰ Protein A on the surface of S aureus binds to the Fc portion of IgG in a nonphysiologic manner, inhibits phagocytosis.

Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins A, B, C1-3, D, E, G, and H act as superantigens, suppressing B cells while inducing T-cell proliferation, cytokine, and tumor necrosis factor release. The enterotoxins are responsible for the symptoms seen in food poisoning. Enterotoxins B and C are structurally very similar to TSST-1 and may be responsible for toxic shock syndrome in the absence of TSST-1. The hemolysins as well as phospholipase C and hyaluronidase enhance spreading and tissue invasion.⁶² The exfoliative toxins, exfoliatin A and B, are responsible for erythroderma and skin separation seen in staphylococcal scalded-skin syndrome.^63,64

ANTIBIOTIC-RESISTANT STAPHYLOCOCCUS AUREUS

Since the mid-1970s, methicillin resistance among hospital-acquired S aureus (HA-MRSA) isolates has increased from less than 5% to more than 50%.⁴¹ Among these isolates, methicillin/oxacillin resistance is conveyed by the presence of a unique transpeptidase that serves as penicillin-binding protein 2a (PBP2a), the product of the chromosomal mecA, which also confers cross-resistance to other β-lactam antibiotics, including currently available cephalosporins. In addition, HA-MRSAs are usually resistant to multiple other classes of drugs due to multiple other resistance genes carried in the mobile staphylococcal chromosome cassette (SCC). Recognized risks associated with HA-MRSA infections include prior antibiotic therapy and exposure to health care environments. Since the mid-1990s, a community acquired MRSA (CA-MRSA) has emerged, with a novel SCC mec that is smaller and does not contain multiple other resistance genes. These isolates, while resistant to all β-lactam antibiotics, usually maintain susceptibility to trimethoprim-sulfamethoxazole, and often clindamycin and tetracyclines. Genotyping of MRSA strains using pulse-field gel electrophoresis demonstrates a single lineage, USA 300, as the predominate clone associated with community outbreaks in the United States.^65-67 USA 300 is distinctly different from other MRSA strains and is more likely to encode for Panton-Valentine leukocidin (PVL),^68,69 the expression of which, while associated with more severe invasive disease, may only be a marker for additional virulence factors.^60,70-73 Vancomycin has been the mainstay of treatment for these severe infections in pediatrics, but resistance to this agent is now observed. S aureus with reduced susceptibility to vancomycin, referred to as vancomycin intermediate S aureus (VISA), have been isolated from patients with significant underlying diseases for which they had received long-term therapy for MRSA with vancomycin.⁷⁴ The genetics of resistance have not been established, but VISA strains exhibit increased extracellular material associated with the cell.⁷⁴Staphylococcus aureus with high levels of resistance to vancomycin (VRSA) were first seen in 2002.⁷⁵ Since 2002, the limited number of VRSA isolates have occurred in patients with both MRSA and vancomycin-resistant enterococcus (VRE).⁷⁶ The mechanism of resistance in VRSA has been the presence vanA, the gene that mediates resistance to vancomycin in enterococci.⁷⁷

CLINICAL MANIFESTATIONS

Skin and Soft Tissue Infection

Staphylococcal impetigo may appear as erythematous-crusted papules and pustules, often at the site of minor trauma such as an insect bite, and may be indistinguishable from infection caused by pyogenic streptococci. Bullous impetigo is more classically staphylococcal in origin and appears as flaccid coalescent pustules and bullae on previously undamaged skin.⁷⁸ Cleavage of the skin in bullous impetigo occurs at a very superficial layer mediated by the local production of enterotoxins A and B, and does not result in scarring, unlike infections involving deeper skin layers. The appearance of S aureus and especially community-acquired methicillin-resistant S aureus (CA-MRSA) infections among healthy newborns warrants review of infection prevention practices in the nursery settings.⁷³ Furuncles occur when focal infection involves the hair follicle and surrounding tissues; carbuncles occur when multiple furuncles coalesce. Necrotic lesions, commonly mistaken for spider bites, have been described in association with deeper CA-MRSA infections.⁷⁸ Recurrent furunculosis and soft tissue abscesses are also associated with CA-MRSA and result in frequent emergency room visits.⁷⁹

The increasing prevalence of CA-MRSA has been associated with an increase in deep soft tissue infections such as myositis, pyomyositis,^80,81 necrotizing fasciitis,^71,82,83 and thrombophlebitis.⁸⁴ It is important to remember that recurrent staphylococcal infections may also be a sign of an underlying granulocyte dysfunction, notably chronic granulomatous disease.

Bacteremia and Sepsis

Staphylococcus aureus bacteremia may occur as a primary event in a normal host or may be in association with underlying wound infection, pneumonia, hemodialysis, or continuous ambulatory peritoneal dialysis (CAPD),²⁷ as well as those with indwelling central venous catheters or underlying conditions such as diabetes, immune deficiencies, or intravenous drug use.^39,40 Bacteremia without a source should raise suspicion for an undiagnosed occult deep site including osteoarticular or endovascular infection. Staphylococcus aureus is responsible for 20% of neonatal intensive-care-unit bacteremias,²⁵ usually catheter associated, and frequently with metastatic foci.⁸⁵ Up to 40% of catheter-related S aureus bacteremias in cancer patients are associated with systemic or metastatic complications.⁸⁶ Septic shock, disseminated intravascular coagulation, septic thromboses, osteoarticular infections, endocarditis, meningitis, acute respiratory distress syndrome, and death may complicate S aureus bacteremia.^86,87 In bacteremia where an intravascular catheter is implicated, it is important to remove the device. Failure to remove a catheter that is associated with S aureus bacteremia increases the risk of metastatic complications.^88-90 Rapidly positive blood cultures for S aureus likely reflect increased bacterial loads that are associated with prolonged bacteremia, endovascular source, increased complications (metastatic infections), and increased mortality.^91-93Staphylococcus aureus bacteremia occurring on multiple successive days is associated with poor outcomes.⁹⁴ Metastatic seeding of secondary sites may occur in as many as half of all patients and recognition of the distant site may be delayed.

Bone and Joint Infections

Staphylococcus aureus is the most common cause of osteomyelitis in children.⁹⁵ Hematogenous seeding of the metaphysis of long bones, often with a history of antecedent minor trauma, is typical. Bacteremia is present in about 50% of cases. Community-acquired methicillin-resistant S aureus (CA-MRSA) strains appear to be associated with the development of deep venous thrombosis in association with osteomyelitis, from which septic emboli may rapidly develop.⁹⁶ Radiographic evidence of periosteal reaction or bone lucencies may not be apparent until well into the second week of infection. Magnetic resonance imaging (MRI) of focal physical findings may facilitate early aspirate and biopsy for culture confirmation in nonbacteremic patients.

Staphylococcus aureus is also the most common cause of pyogenic arthritis in children,⁹⁷ and may occur as an extension of intracapsular metaphyseal bone infection (ie, at the elbow, shoulder, or hip) or may occur as an independent complication of staphylococcal bacteremia. Presentation is usually acute. Adequate drainage of the joint, either open or closed, is essential to minimize joint destruction. Removal of any prosthetic material is usually required.

Lower Respiratory Tract Infections

Staphylococcus aureus can cause rapidly progressive necrotizing pneumonia, more commonly complicating community-acquired methicillin-resistant S aureus (CA-MRSA) bacteremia than bacteremia with other strains.⁹⁸ Enhanced inflammatory responses and extensive tissue destruction have been associated with Panton-Valentine leukocidin (PVL) expressing strains of S aureus, dominated by CAMRSA.^60,71,72 The presence of pneumatoceles on a chest radiograph is strongly suggestive of staphylococcal disease. Pleural effusions and empyema accompany most cases and necessitate drainage for prompt resolution.^99,100

Endocarditis

Staphylococcus aureus is a leading cause of infective endocarditis (IE). The prevalence of IE among pediatric patients with S aureus bacteremia may be as high as 12%.^101,102 The risk of acquiring IE is highest among patients with valvular heart disease, congenital heart disease, prosthetic cardiac valves, and among intravenous drug abusers. Infective endocarditis (IE) that develops in association with a chronic catheter is associated with greater long-term mortality.¹⁰³ Bacteremia in association with S aureus IE may be sustained (≥ 7 days) even with appropriate antibiotics. Embolisms are common and may be peripheral or central. Neurologic sequelae are common with mitral and prosthetic valve involvement. Cardiac complications are especially common with aortic valvular involvement and include valvular destruction, myocardial abscess and fistula formation, and development of conduction abnormalities. Hematogenous dissemination to any tissue may occur (see Chapter 490).¹⁰⁴

Central Nervous System Infections

Staphylococcal central nervous system infections are associated with neurosurgical procedures, penetrating trauma, foreign bodies, direct extension from a contiguous site, and hematogenous dissemination from a distant site. Shunt infections, meningitis, brain abscess, subdural empyema, and epidural abscesses may occur.^105-107 Primary staphylococcal infection of the central nervous system (CNS) is rare.¹⁰⁸ Cyanotic congenital heart disease poses a significant risk for brain abscess, due to staphylococci as well as other organisms.¹⁰⁸ Because the earliest symptoms in young children are nonspecific, the diagnosis of epidural abscess is often delayed until signs of cord compression are present.

Surgical Wound and Foreign Body Infections

The risk of staphylococcal wound infection following surgery increases in the presence of underlying chronic disease, immunodeficiency, and in the presence of a foreign body. Local and systemic complications include wound dehiscence, tissue abscesses, septic thrombophlebitis, bacteremia, sepsis, and metastatic infections. Primary treatment of surgical wounds is debridement. Foreign bodies involved with staphylococcal infections generally must be removed; antibiotics are adjunctive.

Staphylococcus aureus is a major cause of morbidity and mortality in hemodialysis patients. Local infection at the access site may progress to abscess formation and be complicated by bacteremic disease. Staphylococcus aureus is a leading cause of exit- and tunnel-site infections in patients on chronic peritoneal dialysis as well.¹⁰⁹ Nasal carriage of S aureus appears to be a major risk factor for subsequent infections in each of these patient groups. Staphylococcus aureus is second to coagulase-negative staphylococci (CoNS) as a causative agent in intravascular device–related infections in other settings.

Toxin-Mediated Syndromes

The most common clinical syndromes associated with extracellular toxins produced by S aureus are toxic shock syndrome (TSS), staphylococcal scalded-skin syndrome (SSSS), and staphylococcal food-borne disease (SFD). Toxic shock syndrome results from infection or colonization with a strain of S aureus that produces staphylococcal enterotoxin(s) TSST-1, SEB, or SEC.^62,110-112 First described in young women in association with tampon use (menstrual TSS), nonmenstrual TSS now accounts for more than half of all cases.^111,114 Unlike streptococcal TSS, staphylococcal TSS is not commonly associated with bacteremia. Symptoms of TSS include fever, headache, chills, vomiting, diarrhea, sore throat, and myalgias. Hypotension, capillary leak syndrome, and respiratory distress may ensue. Diffuse erythroderma resembling sunburn is often described during the course of illness, and desquamation may be a late finding.^110,111 Toxic shock syndrome must be differentiated from septic shock, streptococcal toxic shock, scarlet fever, meningococcemia, Rocky Mountain spotted fever, Kawasaki syndrome, severe drug reactions, leptospirosis, and measles. Early intensive supportive care is essential in the care of TSS. Any identified focus of infection should be drained and treated. Clindamycin is often recommended because of its ability to inhibit protein synthesis, but should not be used alone unless susceptibility data are known.

Staphylococcal scalded-skin syndrome, often referred to as Ritter syndrome in young infants, is a blistering dermatitis mediated by exfoliative toxins enterotoxin A and B.¹¹⁵ Widespread hematogenous dissemination of the toxin produces fever and tender erythema that may rapidly progress to bullae formation. Minimal friction applied to the skin results in sloughing of the superficial layers of skin (Nikolsky sign). Bacteremia may or may not be present (see Figs. 367-8 and 367-9). Protection may be afforded older children by naturally occurring antitoxin antibodies present in up to 50% of 10 year olds.¹¹¹ Thus, a less-severe syndrome resembling streptococcal “scarlet fever” may be seen in older children where sloughing is generally absent, but superficial desquamation is often seen in the convalescent phase.

Staphylococcal food-borne disease is the most common cause of food poisoning in the United States.¹¹⁶ Foods are contaminated by toxin-producing strains of S aureus, including community-acquired methicillin-resistant S aureus (CA-MRSA),¹¹⁷ during preparation and maintained at a temperature suitable for toxin elaboration. The toxin-bearing food is then ingested by unsuspecting individuals. The incubation period for SFD is short, usually less than 4 hours; nausea, vomiting, and abdominal cramps follow. Fever and headache may occasionally be present. In most individuals, the SFD is self-limited, although severe dehydration and prostration and even death may be seen in a few individuals.¹¹⁸ Specific antistaphylococcal treatment is not indicated.

TREATMENT

The emerging problem of antibiotic resistance has complicated the treatment of S aureus infections. Clinicians should be familiar with the local prevalence of community-acquired methicillin-resistant S aureus (CA-MRSA) and take into consideration the potential consequences of treatment failure when planning therapy for suspected S aureus infections. Cultures should be obtained whenever possible to guide therapy.^119,120 When faced with a severely ill patient in whom S aureus infection is suspected, treatment to cover methicillin-resistant strains should be initiated until culture results and susceptibility data are available.

Local skin care and cleansing may no longer be sufficient therapy for minor superficial infections. Topical mupirocin is a useful adjunctive antibacterial therapy for well-circumscribed impetigo, although mupirocin resistance is increasing.¹²¹ Evaluation for potential bacteremia and treatment with systemic antistaphylococcal therapy should be considered for the neonate with bullous impetigo, especially when the prevalence of community-acquired methicillin-resistant S aureus (CA-MRSA) is high or when nursery outbreaks have been reported.

Cellulitis without abscess may be due to either streptococci or staphylococci; therefore, empirical antibiotic therapy for cellulitis should be effective against both. In areas of low MRSA prevalence, antibiotics such as dicloxacillin, cephalexin, cefadroxil, or amoxicillin plus clavulanate may be effective. Soft tissue abscesses have emerged as a common presentation for CA-MRSA. Lesions should be incised and the drainage sent for culture. In many circumstances, drainage and wound care will be sufficient for these lesions.¹²² However, antibiotics should be considered for more severe local disease or when disease has progressed in spite of incision and drainage. Erythromycin-resistant, clindamycin-susceptible strains should be checked for inducible clindamycin resistance by D-test. Clindamycin, doxycycline or minocycline (if over 8 years of age), and trimethoprim-sulfamethoxazole (TMP/SMX) provide coverage for many community-acquired methicillin-resistant S aureus cases (CA-MRSAs). Because of widespread resistance, the macrolides may not provide optimal management for MSSA or MRSA infections. Linezolid, the first of a new class of antibiotics, and the oxazolidinones, while bacteriostatic for S aureus, have been useful for the management of skin and soft tissue infections resulting from MRSA.¹²⁴ Linezolid is virtually 100% bioavailable following oral administration and intravenous and oral dosing are the same. Fluoroquinolones are not optimal for S aureus because resistance develops rapidly.

Vancomycin is the drug of choice for the treatment of severe or limb-threatening infections in pediatrics when MRSA is a possibility. However, because β-lactam agents exhibit superior antistaphylococcal activity over vancomycin,¹²⁷ they should be used in susceptible organisms. Ceftobiprole is an investigational new cephalosporin with promise as the first cephalosporin with activity against methicillin-resistant staphylococci.¹²⁶ Linezolid is an alternative; however, its bacteriostatic properties should be taken into consideration when treating severe infections. There is limited experience with linezolid in the treatment of bone and joint infections.^129,130 Daptomycin, a novel bactericidal lipopeptide, has been approved in adults to treat infections caused by antibiotic-resistant gram-positives including MRSA¹³¹; however, experience in pediatrics is limited.¹³² Daptomycin is only available in an intravenous (IV) formulation. The rapid bactericidal activity of daptomycin makes it attractive for treatment of MRSA endocarditis and endovascular disease.¹³³ Daptomycin offers once-a-day dosing; however, it is not indicated for the treatment of pneumonia and has not been approved for pediatrics.

Duration of therapy is dependent upon the nature of the infection. For limited skin and soft tissue infections, oral therapy for 5 to 7 days is usually sufficient.¹³⁴ Initial treatment with a parenteral agent should be considered in patients suspected of having a more serious disease. For moderate to severe soft tissue infections such as pyomyositis, 10 to 14 days of antibiotics are recommended with evidence of appropriate clinical response.¹³⁴ Treatment of catheter-associated bacteremia should last at least 14 days.^86,135 Septic arthritis should be treated for at least 3 weeks and osteomyelitis should be treated for at least 4 to 6 weeks, although shorter courses have been advocated.^136,137 Combination therapy with an aminoglycoside (gentamicin) or rifampin are sometimes advocated for severe infections. Data supporting the addition of gentamicin for more than 3 to 5 days are lacking. Clindamycin should not be used in staphylococcal endocarditis. In general, staphylococcal endocarditis should be treated at least 6 weeks with a bactericidal agent or combination.¹³⁸

PREVENTION

To date, there are no data to support the routine attempt to eradicate staphylococcal colonization. However, eradication of the carrier state may be desirable in certain patients at high risk or with a history of repeated staphylococcal infections, or in order to terminate outbreaks in a health care setting.¹³⁹ Regimens are not standardized.¹⁴⁰ Decolonization strategies have been employed including topical 2% mupirocin applied to the nasal vestibules alone or in combination with antiseptic baths, hand sanitizing, hot water laundering, and the daily sanitizing of razors and other personal items.^141-143 Dialysis patients may receive some benefit, although mupirocin resistance emerges with prolonged use. A 5- to 7-day regimen of nasal mupirocin in combination with daily bathing using a 2% chlorhexidine gluconate has been advocated as a preoperative regimen to reduce postoperative infections.¹⁴⁴ A similar strategy combined with either oral rifampin or doxycycline has been used to reduce transmission and to decrease infections in a hospital outbreak setting.¹⁴² Repeated or prolonged use of either mupirocin or antibiotics is discouraged because of the likely emergence of resistance. In general, prevention strategies that focus on good personal hygiene should be advocated first.

REFERENCES

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