Chapter 24: Staphylococci

Although staphylococci have a marked tendency to form clusters (from the Greek staphyle, bunch of grapes), some single cells, pairs, and short chains are also seen. Staphylococci have a typical gram-positive cell wall structure. Like all medically important cocci, they are nonflagellate, nonmotile, and non–spore-forming. Staphylococci grow aerobically but are facultatively anaerobic. In contrast to streptococci, staphylococci produce catalase. More than one dozen species of staphylococci colonize humans; of these, S aureus is by far the most virulent. The ability of S aureus to form coagulase separates it from other, less virulent species (Table 24–1). It is common to lump the other species together as coagulase-negative staphylococci (CoNS).

STAPHYLOCOCCUS AUREUS

BACTERIOLOGY

STRUCTURE

In growing cultures, the cells of S aureus are uniformly gram-positive and regular in size, fitting together in clusters with the uniformity of a rack of billiard balls. In older cultures, in resolving lesions, and in the presence of some antibiotics, the cells often become more variable in size, and many lose their gram positivity.

The cell wall of S aureus consists of a typical gram-positive peptidoglycan interspersed with considerable amounts of teichoic acid. The peptidoglycan of the cell wall is commonly overlaid with polysaccharide and surface proteins. Polysaccharide capsules are present in most strains. Although they are antiphagocytic and increase virulence in animal models their significance in human infections is unknown. Surface proteins such as clumping factors (Clfs), which bind to fibrinogen, and fibronectin-binding proteins (FnBPs) likely play a role in the early stages of infection. Another protein, surface protein A (SpA), is unique in that it binds the Fc portion of IgG molecules, leaving the antigen-reacting Fab portion directed externally (turned around). It is present in most clinical isolates of S aureus. SpA is also able to stimulate cytokines (TNF-α), platelets, and activate B cells.

Metabolism

After overnight incubation on blood agar, S aureus produces white colonies that tend to turn a buff-golden color with time, which is the basis of the species epithet aureus (golden). Most, but not all, strains show a rim of clear β-hemolysis surrounding the colony. The most important laboratory test used to distinguish S aureus from other staphylococci is the production of coagulase, an enzyme which binds prothrombin in a manner that provides for the cleavage of fibrinogen to fibrin. It is demonstrated by incubating staphylococci in plasma; this produces a fibrin clot in a few hours.

TOXINS AND BIOLOGICALLY ACTIVE EXTRACELLULAR ENZYMES

Toxins

Staphylococcus aureus produces a number of named cytolytic toxins (α, β, δ, γ), of which α-toxin is the most important. α-Toxin, is a protein secreted by almost all strains of S aureus, but not by coagulase-negative staphylococci. It is a pore-forming cytotoxin (see Figure 22-6) that lyses the cytoplasmic membranes by direct insertion into the lipid bilayer to form transmembrane pores (Figure 24–2). The resultant egress of vital molecules leads to cell death. This action is similar to streptolysin O, complement, and the effector proteins of cytotoxic T-lymphocytes. α-Toxin is not active against neutrophils but does lyse a wide variety of other cells including keratinocytes. Another pore-forming toxin is active against neutrophils and thus long ago named Panton-Valentine leukocidin (PVL). PVL is also active against platelets. It causes tissue necrosis but until recently was found in only a small portion of clinical isolates (less than 10%). β-Toxin, a sphingomyelinase, is toxic to immune cells in concert with superantigens.

Exfoliatin

Exfoliatin is produced by a small proportion of S aureus strains. It binds to a specific cell membrane ganglioside found only in the stratum granulosum of the keratinized epidermis of the skin. There it causes intercellular splitting of the epidermis between the stratum spinosum and stratum granulosum, presumably by disruption of intercellular junctions. The toxin itself is a protease which acts on desmosomes important to interkeratinocyte adhesion. Two variants of exfoliatin are antigenic in humans, and the circulating antibody confers immunity to their effects.

Staphylococcal Superantigen Toxins

The superantigens (SAgs) are a family of secreted proteins that are able to stimulate systemic effects as a result of absorption from the gastrointestinal tract after ingestion or at a site where they are produced in vivo by multiplying bacteria. There are now more than 15 described staphylococcal superantigen toxins (StaphSAgs), the most important of which in human disease are antigenic variants of the long-known staphylococcal enterotoxins (SEA, SEB, etc) and the more recently discovered toxic shock syndrome toxin (TSST-1). An individual strain may produce one or more toxins, but less than 20% of S aureus strains produce any StaphSAg. As superantigens they are strongly mitogenic for T-cells and do not require proteolytic processing before binding with class II major histocompatibility complex (MHC) molecules on antigen-presenting cells. This process not only bypasses the specificity of antigen processing but results in massive cytokine release due to the ability of these superantigens to activate up to 20% of the total T-cell pool. The StaphSAg toxins share physiochemical and biologic activity similarities with each other and StrepSAgs produced by group A streptococci.

The ability of S aureus enterotoxins to stimulate gastrointestinal symptoms (primarily vomiting) in humans and animals has long been known. Once formed, these toxins are quite stable, retaining activity even after boiling or exposure to gastric and jejunal enzymes. In addition to their superantigen actions, they appear to act by stimulating reflexes in the abdominal viscera, which are transmitted to medullary emetic centers in the brain stem via the vagus nerve. The mechanism of the StaphSAg action on the intestinal mucosa is unknown.

STAPHYLOCOCCAL DISEASE

In many ways, S aureus is the “all-time champion” of microbial pathogens. Although tuberculosis and malaria have greater global prevalence and the spread of AIDS is more ominous, the ferocity of staphylococcal infections has remained constant for as long as we can tell. In Shakespeare’s King Lear (1606), quoted above, Lear is not himself infected. He has just chosen two prototype staphylococcal lesions (boil, carbuncle) as the vilest of symbols to characterize his ungrateful daughters and his treatment at their hands. Today, in any hospital in the world S aureus still heads the list of pathogens isolated from the bloodstream of seriously ill patients.

EPIDEMIOLOGY

The basic human habitat of S aureus is the anterior nares. Ten to thirty percent of the population carry the organism at this site at any given time, and rates among hospital personnel and patients may be much higher. From the nasal site, the bacteria are shed to the exposed skin and clothing of the carrier and others with whom they are in direct contact. Spread is augmented by touching the face and, of course, nose picking. It is blocked by handwashing. Once present on the skin, even transiently, S aureus can gain deeper access either through skin appendages or trauma (Figure 24–3). Although outbreak investigations show that some strains have enhanced virulence, no laboratory tests can separate these strains from those found in the large pool of colonized individuals.

Most S aureus infections acquired in the community are autoinfections with strains that the subject has been carrying in the anterior nares, on the skin, or both.

Community outbreaks are usually associated with poor hygiene and fomite transmission from individual to individual. Unlike many pathogenic bacteria, S aureus can survive periods of drying; for example, recurrent skin infections can result from use of clothing contaminated with pus from a previous infection.

Hospital outbreaks caused by a single strain of S aureus most commonly involve patients who have undergone surgical or other invasive procedures. The source of the outbreak may be a patient with an overt or unapparent staphylococcal infection (eg, decubitus ulcer), which is then spread directly to other patients on the hands of hospital personnel. A nasal or perineal carrier among medical, nursing, or other hospital personnel may also be the source of an outbreak, especially when carriage is heavy and numerous organisms are disseminated. The most hazardous source is a medical attendant who works despite having a staphylococcal lesion such as a boil. Hospital outbreaks of S aureus infection can be self-perpetuating: infected patients and those who attend them frequently become carriers, and the total environmental load of the causative staphylococcus is increased.

Staphylococcal food poisoning is one of the most common foodborne illnesses in the world. It has been an unhappy and embarrassing sequel to innumerable group picnics and wedding receptions in which gastronomic delicacies have been exposed to temperatures that allow bacterial multiplication. Characteristically, the food is moist and rich (eg, red meat, poultry, creamy dishes). The food becomes contaminated by a preparer who is a nasal carrier or has a staphylococcal lesion. If the food is left unrefrigerated for hours between preparation and serving, the staphylococci are able to multiply and produce enterotoxin in the food. Because of the heat resistance of the toxin, toxicity persists even if the food is subsequently cooked before eating.

PATHOGENESIS

Primary Infection

A boil (furuncle) is an abscess and a prototype for the purulent lesions produced by many other bacteria. The initial stages of attachment by S aureus are mediated by a number of surface proteins, which bind to elements on the host cell to their surface. Proteins that bind to the glycoprotein fibronectin that is ubiquitous on mucosal surfaces are of particular importance in the early stages of infection. The staphylococcal fibronectin binding proteins (FnBPs) mediate adhesion to and perhaps invasion of mammalian cells. This allows S aureus to persist and to produce α-toxin and other cytolysins, which injure the cell (Figure 24–4). As the lesions become destructive and spread below the surface, other proteins that bind to collagen and other elements of the extracellular matrix may play a role. At this stage, actions of coagulase and Clfs on fibrinogen-binding, and the antiphagocytic effect of protein A binding to IgG, all combine to limit the effectiveness of host phagocytes. If the strain produces PVL the compromise of innate cellular defenses would be enhanced. The continued production of α-toxin destroys keratinocytes, other cells, and platelets thus compromising repair and allowing the lesion to expand. The inflammatory cells, fibrin, and other tissue components form a wall, which becomes the painfully familiar boil (Figure 24–5). A carbuncle (Figure 24–6) is an extension of this process in which, rather than discharging at the surface, the process forms multiple compartments. There is evidence that S aureus can regulate this multifactored process deploying adhesions and extracellular products at the stages they are needed.

The fate of the lesion depends on the ability of the host to localize the process, which differs depending on the tissue involved. In the skin, spontaneous resolution of the boil by granulation and fibrosis is the rule. In the lung, kidney, bone, and other organs, the process may continue to spread with satellite foci and involvement of broad areas. In all instances, the action of the cytotoxins is highly destructive, creating cavities and massive necrosis with little respect to anatomic boundaries. In the worst cases, the staphylococci are not contained, spreading to the bloodstream and distant organs. Circulating staphylococci may also shed cell wall peptidoglycans, producing massive complement activation, leukopenia, thrombocytopenia, and a clinical syndrome of septic shock. Recent studies implicate a new player, enterotoxin P, which inhibits neutrophil function as a mediator of bacteremia.

Toxin-mediated Disease

If the strain of S aureus causing any of the effects described above also produces one or more of the exotoxins, those actions are added to those of the primary infection. The primary infection serves as a site for absorption of the toxin and need not be extensive or even clinically apparent for the toxic action to occur. In staphylococcal food poisoning, there is no infection at all. The contaminating bacteria produce StaphSAg in the food, which can initiate its enterotoxic action on the intestine within hours of its ingestion.

The in vivo production of exfoliative toxin takes at least a few days and may exert its effect locally or systemically. Toxin absorbed at the infection site reaches its infant stratum granulosum binding site through the circulation causing widespread desquamation by its action on the keratinized epidermis as in the staphylococcal scalded skin syndrome (Figure 24–7A and B). In older children, exfoliative toxin-producing strains may also cause a localized blister-like lesion called bullous impetigo.

In staphylococcal TSS, TSST-1 is produced during the course of a staphylococcal infection with systemic disease as a result of absorption of toxin from the local site. In comparison with other StaphSAgs, TSST-1 is more readily adsorbed across mucosal membranes. Menstruation-associated TSS requires a combination of improbable events. At any one time, less than 15% of women carry S aureus in their vaginal flora, and less than 20% of these have the potential to produce TSST-1. During menstruation, the relatively high protein level and pH in the vagina favor accelerated growth of these staphylococci. In the presence of such a strain, the combination of menstruation and the composition of high-absorbency tampons provide pH and ionic conditions that enhance both the growth of the staphylococci and the production of TSST-1. Toxin absorbed from the vagina can then circulate to produce the multiple effects of massive superantigen-mediated cytokine release (Figure 24–8).

Some cases of full-blown staphylococcal TSS are associated with strains that do not produce TSST-1. This is particularly true of nonmenstrual cases. Other StaphSAgs have been detected in these strains and have been shown to produce experimental toxic shock. TSS may be the result of in vivo production of any of the StaphSAgs, with TSST-1 simply the most common offender. The mechanisms by which the pyrogenic exotoxins produce the multiple renal, cutaneous, intestinal, and cardiovascular manifestations of TSS are not known.

IMMUNITY

The natural history of staphylococcal infections indicates that immunity is of short duration and is incomplete. Chronic furunculosis, for example, can recur over many years. The relative roles of humoral and cellular immune mechanisms are uncertain, and attempts to induce immunity artificially with various staphylococcal products have been disappointing at best. Women suffering menstruation-associated TSS, often have low or absent antibody levels to TSST-1 and often fail to mount a significant antibody response during the disease. This may be due to SAgs stimulation of T_H1 responses with minimal T_H2 component.

STAPHYLOCOCCAL INFECTIONS: CLINICAL ASPECTS

MANIFESTATIONS: PRIMARY INFECTION

Furuncle and Carbuncle

The furuncle or boil (Figure 24–5) is a superficial skin infection that typically develops in a hair follicle, sebaceous gland, or sweat gland. Blockage of the gland duct with inspissation of its contents causes predisposition to infection. Furunculosis is often a complication of acne vulgaris. Infection at the base of the eyelash gives rise to the common stye. The infected patient is often a carrier of the offending Staphylococcus, usually in the anterior nares. The course of the infection is usually benign, and the infection resolves upon spontaneous drainage of pus. No surgical or antimicrobial treatment is needed. Infection can spread from a furuncle with the development of one or more abscesses in adjacent subcutaneous tissues. This lesion, known as a carbuncle, occurs most often on the back of the neck (Figure 24–6), but it may involve other skin sites. Carbuncles are serious lesions that may result in bacteremia.

Chronic Furunculosis

Some individuals are subject to chronic furunculosis, in which repeated attacks of boils are caused by the same strain of S aureus. There is little, if any, evidence of acquired immunity to the disease; indeed, delayed-type hypersensitivity to staphylococcal products appears responsible for much of the inflammation and necrosis that develops. Chronic staphylococcal disease may be associated with factors that depress host immunity, especially in patients with diabetes or congenital defects of polymorphonuclear leukocyte function. However, in most instances, predisposing disease other than acne is not present.

Impetigo

Staphylococcus aureus has been long known as a secondary invader in group A streptococcal pustular impetigo (see Chapter 25), but is increasingly seen producing the skin pustules of impetigo on its own. Strains of S aureus that produce exfoliatin cause a characteristic form called bullous impetigo, characterized by blisters containing many staphylococci in the superficial layers of the skin.

Deep Lesions

Staphylococcus aureus can cause a wide variety of infections of deep tissues by bacteremic spread from a skin lesion that may be unnoticed. These include infections of bones, joints, deep organs, and soft tissues, including surgical wounds. Staphylococcus aureus is the most common cause of all forms of osteomyelitis and is responsible for over 90% of the form of this disease erupting in the long bones of children. Staphylococcal pneumonia is typically secondary to some other insult to the lung, such as influenza, aspiration, or pulmonary edema. A new necrotizing pneumonia has been associated with strains producing PVL. At deep sites, the organism has the same tendency to produce localized, destructive abscesses as it does in the skin. All too often the containment is less effective, and spread with multiple metastatic lesions occurs. Bacteremia and endocarditis can develop. All are serious infections that constitute acute medical emergencies. In all these situations, diabetes, leukocyte defects, or general reduction of host defenses by alcoholism, malignancy, old age, or steroid or cytotoxic therapy can be predisposing factors. Severe S aureus infections, including endocarditis, are particularly common in drug abusers using injection methods.

MANIFESTATIONS CAUSED BY STAPHYLOCOCCAL TOXINS

Scalded Skin Syndrome

Staphylococcal scalded skin syndrome results from the production of exfoliatin in a staphylococcal lesion, which can be minor (eg, conjunctivitis). Erythema and intraepidermal desquamation takes place at remote sites from which S aureus cannot be isolated (Figure 24–7). The disease is most common in neonates and children less than 5 years of age. The face, axilla, and groin tend to be affected first, but the erythema, bullous formation, and subsequent desquamation of epithelial sheets, can spread to all parts of the body. The disease occasionally occurs in adults, particularly those who are immunocompromised.

Toxic Shock Syndrome

Toxic shock syndrome (TSS) was first described in children, but came to public attention during the early 1980s when hundreds of cases were reported in young women using intravaginal tampons. The disease is characterized by high fever, vomiting, diarrhea, sore throat, and muscle pain. Within 48 hours, it may progress to severe shock with evidence of renal and hepatic damage. A skin rash may develop, later followed by desquamation at a deeper level than in scalded skin syndrome. Blood cultures are usually negative. With the withdrawal of certain brands of highly absorbent tampons the annual TSS rate in the United States dropped from 13 to 1 case per 100 000 menstruating women. The overall (menstruating and nonmenstruating) rate is well below that.

Staphylococcal Food Poisoning

Ingestion of staphylococcal enterotoxin-contaminated food results in acute vomiting and diarrhea within 1 to 5 hours. There is prostration, but usually no fever. Recovery is rapid, except sometimes in the elderly and in those with another disease.

DIAGNOSIS

Laboratory procedures to assist in the diagnosis of staphylococcal infections are quite simple. Most acute, untreated lesions contain numerous polymorphonuclear leukocytes and large numbers of gram-positive cocci in clusters. Staphylococci grow overnight on blood agar incubated aerobically. Catalase and coagulase tests performed directly from the colonies are sufficient for identification. In clinical laboratories the coagulase test (tube coagulase) is used only to confirm more convenient rapid slide tests which have a high correlation with the classic test. The rapid tests are based on the detection of Clf, protein A, and other structures unique to S aureus. Staphylococcus aureus isolates can be subdivided by a variety of typing systems and by their pattern of lysis by bacteriophages (phage typing). In epidemiologic investigations, molecular methods such as pulsed field gel electrophoresis are now used to “fingerprint” the spread of virulent clones. Antibiotic susceptibility tests are indicated because of the emerging resistance to multiple antimicrobials, particularly methicillin-resistant S aureus (MRSA). Deep staphylococcal infections such as osteomyelitis and deep abscesses present special diagnostic problems when the lesion cannot be directly aspirated or surgically sampled. Blood cultures are usually positive in conditions such as acute staphylococcal arthritis, osteomyelitis, and endocarditis, but less often in localized infection such as deep abscesses.

TREATMENT

Most boils and superficial staphylococcal abscesses resolve spontaneously without antimicrobial therapy. Those that are more extensive, deeper, or in vital organs require a combination of surgical drainage and antimicrobials for optimal outcome. Since the introduction of penicillin the antimicrobial side of this equation has resembled an arms race between the ability of S aureus to develop resistance and the ability of drug companies to overcome it with a new antibiotic.

STAPHYLOCOCCAL RESISTANCE

When penicillin was introduced to the general public after World War II, virtually all strains of S aureus were highly susceptible. Since then, the selection of preexisting strains containing a plasmid coding for a penicillinase. This enzyme opens the β-lactam ring, making the drug unable to bind with its target. The vast majority of isolates are now penicillin resistant.

Alterations in the β-lactam target, the peptidoglycan transpeptidases (often called penicillin-binding proteins, or PBPs), are the basis for resistance to methicillin. These MRSA strains are also resistant to the newer penicillinase-resistant penicillins such as oxacillin and nafcillin which are now preferred over methicillin. The most common genetic mechanism is the acquisition of a gene (mecA) coding for a new transpeptidase (PBP 2a), which has reduced affinity for β-lactam antibiotics, but is still able to carry out its enzymatic function of cross-linking peptidoglycan.

MRSA

The incidence of MRSA has great geographic variation but rates of 50% or higher are now common.

Laboratory susceptibility tests are performed under technical conditions that facilitate detection of what may be a small resistant subpopulation, and the results extrapolated to other relevant agents. For example, oxacillin resistance is considered proof of resistance to nafcillin and all cephalosporins. Methods for direct detection of the mecA gene have been developed but face the interpretive dilemma that the gene may be present in phenotypically susceptible isolates. Recent evidence shows that such strains may revert to MRSA during treatment and thus should be considered resistant. Vancomycin is often used to treat serious infections with MRSA. The recent emergence of S aureus with decreased susceptibility to vancomycin is still uncommon but of great concern.

MRSA originally associated primarily with hospitals have increasingly emerged in the community (CA-MRSA). At least one clone of CA-MRSA emerging in the United States (USA300) has distinctive pathogenic features beyond methicillin resistance. These strains produce particularly aggressive skin and soft tissue infections. This may be due to the almost universal presence of PVL in these isolates. These and similar clones have been detected in Europe but at a lower rate than in the United States.

ANTIMICROBIAL SELECTION

Although penicillin G is still effective for susceptible strains, it has disappeared from empiric therapy consideration due to the high rate of β-lactamase production as have the penicillinase-resistant penicillins (nafcillin, oxacillin) and cephalosporins (cefazolin, cephalexin) due to the increasing prevalence of MRSA. Once susceptibility has been completed the drug selection depends on (1) the presence of MRSA, (2) the severity of the infection, and (3) any patient history of hypersensitivity to β-lactams. The main MRSA alternatives are vancomycin and daptomycin for deep-seated infections (endocarditis, osteomyelitis, bacteremia, pneumonia) with clindamycin and doxycycline restricted to more superficial skin and soft tissue infections.

PREVENTION

In patients subject to recurrent infection such as chronic furunculosis, preventive measures are aimed at controlling reinfection and, if possible, eliminating the carrier state. Clothes and bedding that may cause reinfection should be dry-cleaned or washed at a sufficiently high temperature (70°C or higher) to destroy staphylococci. In adults, the use of chlorhexidine or hexachlorophene soaps in showering and washing increases the bactericidal activity of the skin. In such individuals, or persons found to be a source of an outbreak, anterior nasal carriage can be reduced and often eliminated by the combination of nasal creams containing topical antimicrobials (eg, mupirocin, neomycin, and bacitracin) and oral therapy with antimicrobials that are concentrated within phagocytes and nasal secretions (eg, rifampin or ciprofloxacin). Attempts to reduce nasal carriage more generally among medical personnel in an institution are usually fruitless and encourage replacement of susceptible strains with multiresistant ones.

Chemoprophylaxis is effective in surgical procedures such as hip and cardiac valve replacements, in which infection with staphylococci can have devastating consequences. Oxacillin, a cephalosporin, or vancomycin given during and shortly after surgery may reduce the chance for intraoperative infection while minimizing the risk for superinfection associated with longer periods of antibiotic administration. Immunization against virulence factors like α-toxin has shown some success in animals. Given the multifactorial nature of S aureus virulence a vaccine seems a long way off.

COAGULASE-NEGATIVE STAPHYLOCOCCI

Other than S aureus, there are more than 40 species of staphylococci. In medical practice, the less than 20 species that have been isolated from human infections are typically lumped together by a negative characteristic—failure to produce coagulase. These coagulase—negative staphylococci (CoNS) also do not produce α-toxin, exfoliatin, or any of the StaphSAg toxins. They have been shown to have surface adhesins and the ability to produce extracellular polysaccharide biofilms. By far the most common CoNS species isolated from human infections is S epidermidis, and S saprophyticus is a significant cause of urinary tract infections. Clinical laboratories rarely speciate CoNS isolates, although a simple test (novobiocin resistance) is often used to separate S saprophyticus from other urinary isolates.

CoNS DISEASE

Staphylococcus epidermidis and many other species of CoNS are normal commensals of the skin, anterior nares, and ear canals of humans. Their large numbers and ubiquitous distribution result in frequent contamination of specimens collected from or through the skin. In the past, they were rarely the cause of significant infections, but with the increasing use of implanted catheters and prosthetic devices, they have emerged as important agents of hospital-acquired infections. Immunosuppressed or neutropenic patients and premature infants have been particularly affected.

Organisms may contaminate prosthetic devices during implantation, seed the device during a subsequent bacteremia, or gain access to the lumina of shunts and catheters when they are temporarily disconnected or manipulated. The outcome of the bacterial contamination is determined by the ability of the microbe to attach to the surface of the foreign body and to multiply there. Central to this process is the ability of these species to form a viscous extracellular polysaccharide biofilm. The biofilm formation involves quorum sensing (see Chapter 22) and in addition to production of polysaccharide includes adhesive proteins and extracellular DNA. Initial adherence is facilitated by the hydrophobic nature of the synthetic polymers used in medical devices and the ability of polysaccharides produced by the organism to mediate attachment both to the plastic and between CoNS cells. As it expands, this biofilm provides additional adhesion, encases the entire bacterial population (Figure 24–9), and serves as a barrier to antimicrobial agents and host defense mechanisms.

The abovementioned circumstances are found almost exclusively in hospitals and other medical facilities. The most common device colonized is the intravenous catheter, but the same mechanisms apply to any implanted device such as cerebrospinal fluid shunts and artificial heart valves. The ensuing disease is typically low grade with little more than a slowly advancing fever to arouse suspicion. Staphylococcus aureus can also produce biofilms, and although a less frequent colonizer of medical devices, it is likely to produce a more aggressive course and metastatic infections. Removal of the contaminated device is the only sure way to avoid these complications.

The biology of S saphrophyticus infection is entirely different. Its usual habitat is the gastrointestinal tract, and from that location the organism gains access to the urinary tract. Among sexually active women, S saphrophyticus is second only to Escherichia coli as a cause of acute urinary tract infection. It is rarely found in men. The infection process is aided by surface adhesins to uroepithelial cells and factors aiding survival in urine like the production of a urease. Thus, although other CoNS are causes of infection among compromised patients in hospitals, S saphrophyticus produces community-acquired infection in women who are otherwise healthy. Staphyloccocus lugdunensis, although rare, produces disease with features more similar to S aureus than the other CoNS. A collection of unique virulence factors may be responsible.

The interpretation of cultures that grow CoNS is difficult. In most cases, the finding is attributable to skin contamination during collection of the specimen. The presence of at least moderate numbers of organisms or repeated isolations from the same site argue for infection over skin contamination. Specimens collected directly from catheters and shunts typically show large numbers of staphylococci. Most CoNS now encountered are resistant to penicillin, and many are also methicillin-resistant. Resistance to multiple antimicrobials usually active against gram-positive cocci, including vancomycin, is more common than with S aureus. Eradication of CoNS from prosthetic devices and associated tissues with chemotherapy alone is very difficult unless the device is also removed.