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Staphylococcal and streptococcal infections
BACTERIAL INFECTIONS
Staphylococcal and streptococcal infections
What’s new? C
ME Torok NPJ Day
C
C
Abstract Staphylococcal and streptococcal infections are common infectious diseases and can range from mild, superficial skin infections to severe, life-threatening systemic infections. Staphylococcus aureus, group A streptococcus, and Streptococcus pneumoniae are the three major pathogens. The prevalence of invasive infections caused by community-associated meticillin-resistant S. aureus and group A streptococcus appears to be increasing. The emergence of drug resistance (e.g. meticillin and glycopeptide resistance in S. aureus, macrolide resistance in group A streptococci and penicillin resistance in S. pneumoniae), is concerning and a potential threat to successful treatment. Streptococcus suis has recently emerged as an important human pathogen.
Community-associated MRSA and Streptococcus suis have emerged as significant human pathogens over the past few years. Increasing antimicrobial resistance among Staphylococcus aureus and Streptococcus pneumoniae isolates is of growing concern and threatens successful treatment of these infections. There are limited data on the use of newer antimicrobial agents (e.g. linezolid, daptomycin and ceftobiprole) in the treatment of MRSA infections.
intrinsically resistant to all b-lactam antibiotics, is a major concern.1 Over the past few years, infections caused by community-associated MRSA (CA-MRSA) in previously healthy people have emerged as a significant clinical problem.2 Another concern is the emergence of isolates with reduced susceptibility or resistance to vancomycin [e.g. vancomycin-intermediate S. aureus (VISA), heterogeneous VISA (hVISA) and vancomycinresistant S. aureus (VRSA)].3 hVISA strains appear to be susceptible to vancomycin but contain a subpopulation of cells resistant to vancomycin. Patients at most risk of infection by hVISA, VISA and VRSA appear to be those with previous exposure to vancomycin.
Keywords community-acquired MRSA; group A streptococci; group B streptococci; Staphylococcus aureus; Streptococcus bovis; Streptococcus pneumoniae; Streptococcus suis; viridans streptococci
Staphylococci Pathogenesis: S. aureus has several putative determinants of pathogenicity, including cell wall constituents, surface proteins, toxins and enzymes, and specific cell wall-bound adhesins. It secretes enzymes, including catalase, coagulase, clumping factor, hyaluronidase, b-lactamases and DNase, and produces extracellular toxins, some of which are directly cytotoxic (haemolysins, leukocidins) and some of which act as superantigens, causing polyclonal proliferation of T cells (toxic shock syndrome toxin-1 (TSST-1), enterotoxins, epidermolytic toxins). The Pantone Valentine leucocidin (PVL) is a cytotoxin that causes leucocyte destruction and tissue necrosis. Although there is a strong epidemiological association of CA-MRSA infections and PVL production, its role in the pathogenesis and spread of infection is controversial. In a mouse sepsis model, PVL-negative strains of CA-MRSA were as lethal as wild-type strains and caused comparable skin disease.4 In a study of 31 strains collected from patients with infections of varying severity, the quantity of PVL production in vitro did not correlate with the severity of infection. Host factors that particularly predispose to S. aureus infection include inborn defects in neutrophil function, diabetes mellitus, and the presence of foreign material. Nasal carriers are more likely to develop nosocomial bacteraemia, though the associated mortality may be lower.
The genus Staphylococcus currently contains 35 species, all of which are part of the normal skin and mucous membrane flora of humans and animals. S. aureus is the most important pathogen, causing various pyogenic infections and toxin-mediated illnesses in normal hosts. Other species are collectively termed ‘coagulasenegative staphylococci’. These are generally considered nonpathogenic, apart from Staphylococcus epidermidis, which causes nosocomial (hospital-associated) bacteraemia and device-related infections, and Staphylococcus saprophyticus, which is a common cause of urinary tract infection. Staphylococcus aureus S. aureus is carried in the anterior nares of 20e40% of adults, depending on seasonal and local epidemiological factors. Some groups (e.g. medical staff, patients with type 1 diabetes, haemodialysis patients, intravenous drug users) appear to be particularly prone to colonization with S. aureus. Carriers transfer the organism to the skin, where trauma can provide a portal of entry, leading to local, deep, or systemic infection. The global spread of meticillin-resistant S. aureus (MRSA), which is
ME Torok MA MRCP FRCPath is a Consultant in Infectious Diseases in the Department of Infectious Diseases, Addenbrooke’s Hospital, Cambridge, UK. Competing interests: none declared.
Microbiology: S. aureus grows rapidly aerobically and anaerobically on blood agar and other non-selective solid media. Most strains are b-haemolytic. Microscopically, S. aureus is apparent as Gram-positive cocci that tend to form clusters on solid media. Identification is usually confirmed by positive catalase, coagulase and DNase tests. Typing is now
NPJ Day MA MRCP is Director of the WellcomeeMahidoleOxford Tropical Medicine Research Programme, Hospital for Tropical Diseases, Bangkok, Thailand. Competing interests: none declared.
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performed by molecular methods (e.g. pulsed-field gel electrophoresis, multi-locus sequence typing, SCCmec typing or spa typing).
Staphylococcal scalded skin syndrome is caused by epidermolytic toxin-producing S. aureus and is usually seen in children. Clinical presentation ranges from bullous impetigo to severe, generalized, exfoliative dermatitis with systemic upset. It is usually treated with intravenous antibiotics, supportive skin care and careful management of fluid and electrolyte losses. Toxic shock syndrome is caused by TSST-1 and other related staphylococcal enterotoxins. The menstrual form is associated with tampon use, the non-menstrual form with vaginal infections, contraceptive devices, abortion, childbirth and surgical procedures. The clinical case definition includes fever, hypotension, desquamating rash and involvement of three or more organ systems. Management requires aggressive fluid resuscitation, removal of any tampon, and parenteral anti-staphylococcal antibiotics.
Clinical manifestations: S. aureus is a major cause of skin and soft-tissue infections including impetigo, ecthyma (ulcerative pyoderma), folliculitis, furuncles, carbuncles, erysipelas, cellulitis and necrotizing fasciitis (see Medicine 37(11), pp. 603e609). Over the past few years, outbreaks of CA-MRSA infection have been reported in children, Alaskan natives, Pacific islanders, prisoners, sports teams and military personnel.2 CA-MRSA has become the most common cause of skin and soft-tissue infections presenting to emergency departments in the USA.5 The incidence of S. aureus bacteraemia, and the proportion of bacteraemic episodes caused by MRSA, has also increased over the past few years.6 It can be divided into two categories: community-acquired bacteraemia (onset <2 days post-hospital admission) and hospital-acquired (onset 2 days after hospital admission). Metastatic infections such as endocarditis, pericarditis, pneumonia, pulmonary abscesses, empyema, septic bursitis, septic arthritis, pyomyositis and discitis osteomyelitis can occur (Figures 1 and 2). The diagnosis is confirmed by cultures of blood and appropriate clinical specimens. Patients with S. aureus bacteraemia should have an echocardiogram to look for endocarditis. Investigations for metastatic infection should be guided by symptoms (e.g. magnetic resonance scan of spine to exclude suspected vertebral discitis or osteomyelitis).
Coagulase-negative staphylococci Coagulase-negative staphylococci (CoNS) are skin commensals. Often dismissed as culture contaminants, they are becoming increasingly recognized as pathogens.7 S. saprophyticus is a common cause of community-acquired urinary tract infection. S. epidermidis causes nosocomial bacteraemia and prosthetic device-related infections. Other species that have been associated with infection include Staphylococcus haemolyticus, Staphylococcus lugdunensis and Staphylococcus schleiferi. These organisms adhere to prosthetic material and become embedded in an exopolysaccharide matrix, forming a biofilm. The biofilm protects the organisms from phagocytic cells and reduces the penetration of antibiotics.
Management: treatment of S. aureus infections depends on the nature of the primary focus and the presence or absence of metastatic infection. Flucloxacillin is the drug of choice in meticillin-sensitive S. aureus (MSSA) infections, whereas vancomycin (or teicoplanin) is used in MRSA infections and penicillin-allergic patients. The role of the newer Gram-positive antimicrobial agents (e.g. linezolid, daptomycin, ceftobiprole) in the treatment of MRSA infections remains to be established. Aminoglycosides exhibit synergistic activity in vitro and are often used in endocarditis and other severe infections. Skin and softtissue infections usually respond to 7e14 days of antibiotic therapy. Deeper infections, such as deep abscesses, septic arthritis or osteomyelitis, often require drainage of the focus and more prolonged antimicrobial therapy. Catheter-related bacteraemia is treated with removal of the catheter and 14 days’ intravenous therapy. Bacteraemia of unknown source or endocarditis is treated with a minimum of four weeks’ intravenous therapy. The treatment of endocarditis is discussed elsewhere (see Medicine 37(11), pp. 582e585). In prosthetic device-related infection, the device should be removed and the infection treated with prolonged (4e6 weeks) intravenous therapy. In cases where the device cannot be removed (e.g. vascular graft infection), oral suppressive antimicrobial therapy should be continued indefinitely.
Microbiology: coagulase-negative staphylococci grow rapidly aerobically and anaerobically on blood agar and other nonselective solid media. Microscopically, they are Gram-positive cocci that form clusters on solid media. Identification is usually confirmed by negative coagulase and DNase tests. Nosocomial isolates usually multiply antibiotic-resistant (mainly plasmidmediated). Typing of coagulase-negative staphylococci is performed by molecular methods, because biochemical tests are unreliable. Clinical manifestations: S. saprophyticus is a common cause of cystitis in young women. It is treated with oral antibiotics (e.g. trimethoprim, nitrofurantoin or ciprofloxacin).
Toxin-mediated diseases: S. aureus can also cause a number of toxin-mediated diseases, such as food poisoning, scalded skin syndrome, and toxic shock syndrome. Staphylococcal food poisoning presents with vomiting and diarrhoea within hours of ingestion of foods containing enterotoxin-producing bacteria. Treatment is symptomatic.
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Figure 1 Psoas abscess caused by Staphylococcus aureus.
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placed taxonomically using molecular techniques such as DNA hybridization and ribosomal RNA sequencing. Group A streptococcus Group A streptococcus (Streptococcus pyogenes) is a major human pathogen, causing acute pharyngitis and variety of cutaneous and systemic infections. There are several pathogenic determinants, including M protein and a hyaluronic acid capsule, both of which are anti-phagocytic. Exotoxins (A, B, C, mitogenic factor and streptococcal superantigen), haemolysins (streptolysins O and S) and enzymes (DNases, hyaluronidase and streptokinase) are also produced.8 Microbiology: group A streptococci grow rapidly aerobically and anaerobically on blood agar and other non-selective solid media and are b-haemolytic. Microscopically, they are Grampositive cocci that grow in pairs or short chains. Identification is usually confirmed by streptococcal grouping using latex agglutination. Clinical manifestations: streptococcal pharyngitis is a common childhood infection, spread by droplet and presenting after a 2e4-day incubation period with fever, sore throat, inflamed pharynx, tonsillar enlargement, and tender regional lymphadenopathy. Treatment is with oral penicillin for 10 days. Group A streptococcus also causes various skin and soft tissue infections, including erysipelas, cellulitis and necrotizing fasciitis, which are described elsewhere (see Medicine 37(11), pp. 603e609). The incidence of severe, invasive infections appears to be increasing9 but the reason for this is not clear. Streptococcal toxic shock syndrome can be defined as any streptococcal infection associated with sudden onset of shock (systolic blood pressure 90 mm Hg) and multi-organ failure (defined as two or more of the following: renal impairment; coagulopathy; hepatic impairment; adult respiratory distress syndrome; generalized rash that may desquamate; soft-tissue necrosis). Streptococcal M protein is thought to have a major role in the pathogenesis by forming complexes with fibrinogen that bind to integrins on the surface of circulating neutrophils. The activated neutrophils cause endothelial cell damage and consequent vascular leakage and hypercoagulability, leading to hypotension and organ damage. Management is with prompt, aggressive surgical debridement of suspected deep-seated streptococcal infection, intravenous broad-spectrum antibiotic therapy, and intensive-care support. Once a streptococcal cause is confirmed, treatment can be rationalized to intravenous benzylpenicillin and clindamycin. Scarlet fever results from infection with an organism that produces an erythrogenic toxin (Figure 3). These toxins are superantigens; two (SPE A and SPE B) resemble S. aureus enterotoxins at the molecular level. A scarlatinal rash occurs, usually on the second day of the illness, and spreads from the upper chest to the trunk, neck and extremities, sparing the palms and soles. The rash fades over one week and is followed by extensive desquamation. Severe forms of disease are characterized by fever and marked systemic toxicity. Treatment is with penicillin. Acute rheumatic fever is an autoimmune disease caused by immunological cross-reactivity between streptococcal M proteins
Figure 2 L1/2 discitis caused by Staphylococcus aureus.
S. epidermidis is the most common cause of nosocomial bacteraemia and is often associated with intravascular catheters or prosthetic material. It is also the most common cause of early prosthetic-valve endocarditis (see Medicine 37(11), pp. 582e585) and cerebrospinal fluid shunt infections. Other infections include peritoneal dialysis catheter-associated peritonitis, bacteraemia in immunocompromised patients and neonates, sternal osteomyelitis, prosthetic joint infections, vascular graft infections and post-surgical endophthalmitis. Management: treatment of coagulase-negative staphylococcal infections usually requires removal of the intravascular catheter or infected prosthetic device and intravenous antibiotic therapy (e.g. vancomycin or teicoplanin). Where the foreign material cannot be removed, prolonged intravenous antibiotic therapy is required, and is often followed by long-term oral suppressive therapy.
Streptococci Streptococci are catalase-negative Gram-positive cocci that grow in pairs or chains. More than 30 species have been identified; those discussed below are the most pathogenic in humans. Classification of streptococci is complex and based on a number of features including haemolysis pattern on blood agar, biochemical reactions, antigenic composition, and genetic analysis. Three patterns of haemolysis are seen on blood agar: partial haemolysis (a-haemolysis); complete haemolysis (b-haemolysis); and non-haemolysis. a-Haemolytic streptococci produce a greenish discoloration of blood agar, hence the term ‘viridans streptococci’. b-Haemolytic streptococci are classified into Lancefield serogroups, determined by antigenic differences between cell wall carbohydrates. Streptococci lacking a recognizable group antigen are identified by their biochemical reactions, and
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and epidural and brain abscesses. Predisposing factors include defects in antibody formation, complement deficiency, neutropenia, hyposplenism, extremes of age, alcoholism, diabetes, and chronic diseases. Pathogenesis: S. pneumoniae has several adhesins that enable it to bind to epithelial cell receptors. It produces a capsule that helps it to evade phagocytosis. ‘C-polysaccharide’ (a teichoic acid constituent of the cell wall containing choline phosphate) is unique to S. pneumoniae and is responsible for the reaction between pneumococci and C-reactive protein, which leads to complement activation. Microbiology: S. pneumoniae grows in chains in liquid media, but often appears on Gram stain as lanceolate diplococci. It is ahaemolytic on blood agar, produces a negative catalase reaction, and is sensitive to optochin. Serotypes are based on antigenic differences between capsular polysaccharides. Resistance to penicillin and macrolides is increasing worldwide, ranging from 1 to 90% in different geographical areas.11 High-level penicillin resistance remains uncommon in the UK (3.8% of invasive isolates in 2007) but resistance to erythromycin is somewhat higher at 9%.12
Figure 3 The rash of scarlet fever in group A streptococcal bacteraemia.
and cardiac antigens, and is a delayed sequela of streptococcal pharyngitis. It mainly affects 6e15-year olds, particularly in the developing world. Non-suppurative inflammatory lesions involve the heart, joints, skin, subcutaneous tissues and central nervous system. Damage to the heart valves can result in progressive valvular lesions and cardiac failure. Diagnosis is based on the revised Jones criteria.10 Treatment is with analgesics and/or anti-inflammatory drugs (aspirin or corticosteroids). Post-streptococcal glomerulonephritis results from crossreactivity between streptococcal M proteins and host antigens, and follows streptococcal pharyngitis or pyoderma. It is an acute inflammatory disorder of the renal glomerulus, associated with diffuse proliferative glomerular lesions and presents with acute renal failure. Diagnosis is based on clinical features and confirmatory evidence of recent streptococcal infection. Treatment is directed towards management of acute problems (e.g. hypertension, fluid overload, acute renal failure) and eradication of the causative organism with penicillin (to prevent further transmission of the nephritogenic clone). The prognosis is good, although a few patients develop chronic glomerulonephritis.
Clinical manifestations: worldwide, S. pneumoniae is the most common cause of otitis media, community-acquired pneumonia and bacterial meningitis. It is also the predominant organism isolated in patients with meningitis following head injury. S. pneumoniae also causes sinusitis, bacteraemia, para-pneumonic effusion, empyema, lung abscess, septic arthritis, osteomyelitis, spontaneous bacterial peritonitis and endocarditis. S. pneumoniae infections are more common in HIV-infected persons and young people presenting with invasive disease should be offered an HIV test. Treatment: the treatment of S. pneumoniae infections depends on the site of infection and drug susceptibility pattern of the organism. Infections such as otitis media and sinusitis can be treated with oral amoxicillin (or moxifloxacin if the patient is penicillin-allergic). Treatment of pneumonia is with oral or intravenous amoxicillin, depending on disease severity. Alternatives in penicillin-allergic patients are doxycycline, erythromycin or clarithromycin. Bacteraemia is treated with intravenous benzylpenicillin. Meningitis is initially treated with intravenous ceftriaxone; vancomycin can be added if there is a high risk of penicillin resistance (e.g. patient from abroad). If the isolate is found to be fully susceptible (penicillin MIC <0.06 mg/L), treatment can be rationalized to benzylpenicillin. If the isolate has intermediate penicillin susceptibility (penicillin MIC 0.12e 1.0 mg/L), treatment should continue with ceftriaxone. Adjunctive corticosteroids have been recommended for the treatment of adult bacterial meningitis,13 but more recent data from the developing world are less supportive of their use.14,15
Group C and G streptococci Group C and G streptococci are b-haemolytic streptococci that colonize the nasopharynx, skin and genital tract and cause infections similar to group A streptococcus. These include pharyngitis, skin and soft-tissue infections, septic arthritis, osteomyelitis, pneumonia, endocarditis, puerperal sepsis, neonatal sepsis and bacteraemia. Post-streptococcal glomerulonephritis has been associated with group C streptococci. The treatment of choice for both group C and G streptococcal infections is penicillin (or vancomycin in penicillin-allergic patients). Penicillin tolerance is a feature of group C streptococci and synergistic gentamicin therapy has been recommended for the therapy of severe infections. Streptococcus pneumoniae S. pneumoniae (pneumococcus) is a common bacterial pathogen of humans found in the nasopharynx of 20e40% of children and 10e20% of adults. Colonization and infection rates are seasonal, increasing during the winter. S. pneumoniae is a major cause of otitis media, sinusitis, pneumonia and meningitis. Less commonly, it causes bacteraemia, peritonitis, endocarditis, pericarditis, septic arthritis, osteomyelitis, soft-tissue infections,
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Prevention: invasive disease can be prevented by vaccination. The pneumococcal polysaccharide vaccine, which contains 23 serotypes, has been recommended in those patients aged >65 years and those at increased risk (e.g. age >65 years, asplenia/hyposplenism, chronic respiratory,
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cardiac, renal or liver diseases, diabetes, immunosuppression, cochlear implants, cerebrospinal fluid leaks). In 2006, the pneumococcal conjugate vaccine, which contains seven serotypes, was added to the UK routine childhood immunization schedule. Group B streptococcus Group B streptococcus (Streptococcus agalactiae) is an important pathogen in pregnancy, post-partum women, and in neonates. The prevalence of asymptomatic vaginal colonization in pregnant women is 5e40%. The rate of vertical transmission in neonates born to women colonized at the time of delivery is 50%. The most devastating infections (bacteraemia and meningitis) occur in neonates, but group B streptococci can also cause bacteraemia in adults.
Figure 4 Purpuric rash in a patient with Streptococcus suis bacteraemia.
the oral cavity. They are considered to be of low pathogenicity, apart from their propensity to adhere to cardiac valves and cause endocarditis. Some species (e.g. Streptococcus mutans) have a strong association with dental caries. Viridans streptococci are facultatively anaerobic, catalasenegative Gram-positive cocci that grow on blood agar and other non-selective solid media, and are mainly a-haemolytic. Although some isolates react with Lancefield grouping antisera, they do not conform to specific serogroups and many isolates are non-groupable. In the past, the terminology applied to the viridans group of streptococci was confusing and inconsistent. Molecular techniques have now enabled genotypic differentiation, which has subsequently been found to correlate with phenotypic differences in biochemical tests. At present, clinically significant species can be assigned to one of the following groups: anginosus group; mitis group; mutans group; salivarius group. The viridans streptococci are a major cause of native valve endocarditis, usually in patients with underlying valve disease. They can also cause bacteraemia (particularly in neutropenic patients), meningitis, and pneumonia. Viridans streptococci were previously uniformly susceptible to penicillin but resistance to penicillin is increasing, particularly in nosocomial bloodstream isolates from immunocompromised patients. Although viridans streptococci are resistant to aminoglycosides (when traditional breakpoints are used), synergistic bactericidal activity has been seen with penicillin and aminoglycosides. Thus, a combination of penicillin and gentamicin is usually used to treat endocarditis (see Medicine 37(11), pp. 582e585).
Microbiology: group B streptococci are facultatively anaerobic, b-haemolytic diplococci that grow readily on various media. Definitive identification is based on detection of the group Bspecific cell wall antigen by latex agglutination. They can be subclassified into nine serotypes based on capsular polysaccharide determinants. Clinical features: group B streptococci are important pathogens in pregnancy and can cause asymptomatic bacteriuria, cystitis or, less often, pyelonephritis. Colonized pregnant women are at significantly increased risk of premature rupture of membranes, post-partum fever, endometritis and wound infection. Rarely, pelvic abscess, septic shock or septic thromboembolism occurs. Group B streptococci are also important causes of neonatal sepsis. Early-onset infection (onset <7 days after birth) is associated with certain maternal risk factors (age <20 years, previous miscarriage, premature or prolonged rupture of membranes, intra-partum fever) and prematurity (delivery at <37 weeks’ gestation) and presents with septicaemia (60%), pneumonia (30%) or meningitis (10%). Mortality is 2e8% in term infants and is inversely proportional to birth weight. Late-onset infection (7 dayse3 months) presents with bacteraemia, meningitis, osteomyelitis or septic arthritis. Uncommon foci include cellulitis, adenitis, otitis media, conjunctivitis, empyema, peritonitis, endocarditis and deep abscesses. Treatment is with high-dose intravenous benzylpenicillin. Invasive group B streptococcal infection causes considerable morbidity and mortality in adults. In the non-pregnant population, the incidence increases with age; men are more commonly affected. Diabetes, liver disease, neurological conditions, malignancy, renal or urological disease, cardiopulmonary disease and HIV infection predispose to invasive infection. Bacteraemia is the most common presentation. Other syndromes include pneumonia, septic arthritis, osteomyelitis, skin and softtissue infections, and meningitis. Treatment of adult infection is with high-dose intravenous benzylpenicillin (or vancomycin in those allergic to penicillin). Mortality in non-pregnant adults is 21e32%.
Streptococcus bovis S. bovis causes endocarditis and bacteraemia, the latter often associated with colonic malignancy or hepatic cirrhosis. It is an a-haemolytic streptococcus and is identified by biochemical tests and Lancefield serogrouping (group D). It is highly susceptible to penicillin, which is the drug of choice. Streptococcus suis S. suis was previously considered to be predominantly an animal pathogen but is increasingly being recognized as a cause of bacterial meningitis and septicaemia in humans (Figure 4).16 In 2005, a large outbreak of 215 cases occurred in China associated with a high mortality rate (62%).17 Predisposing factors include contact with pigs or undercooked pork, alcoholism and splenectomy. The organism is a-haemolytic and is identified by biochemical tests and serotyping. Treatment is with benzylpenicillin. A
Viridans streptococci Viridans streptococci are commensals in the gastrointestinal, respiratory and female genital tracts and are most prevalent in
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REFERENCES 1 Boucher HW, Corey GR. Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008; 46: S344e9. 2 Weber JT. Community-associated methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2005; 41: S269e72. 3 Appelbaum PC. Reduced glycopeptide susceptibility in methicillinresistant Staphylococcus aureus (MRSA). Int J Antimicrob Agents 2007; 30: 398e408. 4 Diep BA, Otto M. The role of virulence determinants in community-associated MRSA pathogenesis. Trends Microbiol 2008; 16: 361e9. 5 King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med 2006; 144: 309e17. 6 Johnson AP, Pearson A, Duckworth G. Surveillance and epidemiology of MRSA bacteraemia in the UK. J Antimicrob Chemother 2005; 56: 455e62. 7 Rogers KL, Fey PD, Rupp ME. Coagulase-negative staphylococcal infections. Infect Dis Clin North Am 2009; 23: 73e98. 8 Bisno AL, Brito MO, Collins CM. Molecular basis of group A streptococcal virulence. Lancet Infect Dis 2003; 3: 191e200. 9 Lamagni TL, Darenberg J, Luca-Harari B, et al. Epidemiology of severe Streptococcus pyogenes disease in Europe. J Clin Microbiol 2008; 46: 2359e67. 10 Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. Special writing group of the committee on rheumatic fever, endocarditis, and Kawasaki disease of the council on cardiovascular disease in the young of the American Heart Association. JAMA 1992; 268: 2069e73.
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11 Van Bambeke F, Reinert RR, Appelbaum PC, Tulkens PM, Peetermans WE. Multidrug-resistant Streptococcus pneumoniae infections: current and future therapeutic options. Drugs 2007; 67: 2355e82. 12 Health Protection Agency. Antimicrobial resistance and prescribing in England. Wales and Northern Ireland: Health Protection Agency, 2008. 13 de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347: 1549e56. 14 Scarborough M, Gordon SB, Whitty CJ, et al. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med 2007; 357: 2441e50. 15 Nguyen TH, Tran TH, Thwaites G, et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med 2007; 357: 2431e40. 16 Wertheim HF, Nghia HD, Taylor W, Schultsz C. Streptococcus suis: an emerging human pathogen. Clin Infect Dis 2009; 48: 617e25. 17 Yu H, Jing H, Chen Z, et al. Human Streptococcus suis outbreak, Sichuan, China. Emerg Infect Dis 2006; 12: 914e20.
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Staphylococci and streptococci are commensal organisms that can cause a wide variety of conditions ranging from skin and soft tissue infections to severe, life-threatening infections Patients who are systemically unwell should be admitted for appropriate investigations and intravenous antibiotic therapy Drug-resistance in these organisms is increasing and empirical antimicrobial therapy may need to reflect this
Ó 2009 Elsevier Ltd. All rights reserved.
Staphylococcal and streptococcal infections
What’s new? C
ME Torok NPJ Day
C
C
Abstract Staphylococcal and streptococcal infections are common infectious diseases and can range from mild, superficial skin infections to severe, life-threatening systemic infections. Staphylococcus aureus, group A streptococcus, and Streptococcus pneumoniae are the three major pathogens. The prevalence of invasive infections caused by community-associated meticillin-resistant S. aureus and group A streptococcus appears to be increasing. The emergence of drug resistance (e.g. meticillin and glycopeptide resistance in S. aureus, macrolide resistance in group A streptococci and penicillin resistance in S. pneumoniae), is concerning and a potential threat to successful treatment. Streptococcus suis has recently emerged as an important human pathogen.
Community-associated MRSA and Streptococcus suis have emerged as significant human pathogens over the past few years. Increasing antimicrobial resistance among Staphylococcus aureus and Streptococcus pneumoniae isolates is of growing concern and threatens successful treatment of these infections. There are limited data on the use of newer antimicrobial agents (e.g. linezolid, daptomycin and ceftobiprole) in the treatment of MRSA infections.
intrinsically resistant to all b-lactam antibiotics, is a major concern.1 Over the past few years, infections caused by community-associated MRSA (CA-MRSA) in previously healthy people have emerged as a significant clinical problem.2 Another concern is the emergence of isolates with reduced susceptibility or resistance to vancomycin [e.g. vancomycin-intermediate S. aureus (VISA), heterogeneous VISA (hVISA) and vancomycinresistant S. aureus (VRSA)].3 hVISA strains appear to be susceptible to vancomycin but contain a subpopulation of cells resistant to vancomycin. Patients at most risk of infection by hVISA, VISA and VRSA appear to be those with previous exposure to vancomycin.
Keywords community-acquired MRSA; group A streptococci; group B streptococci; Staphylococcus aureus; Streptococcus bovis; Streptococcus pneumoniae; Streptococcus suis; viridans streptococci
Staphylococci Pathogenesis: S. aureus has several putative determinants of pathogenicity, including cell wall constituents, surface proteins, toxins and enzymes, and specific cell wall-bound adhesins. It secretes enzymes, including catalase, coagulase, clumping factor, hyaluronidase, b-lactamases and DNase, and produces extracellular toxins, some of which are directly cytotoxic (haemolysins, leukocidins) and some of which act as superantigens, causing polyclonal proliferation of T cells (toxic shock syndrome toxin-1 (TSST-1), enterotoxins, epidermolytic toxins). The Pantone Valentine leucocidin (PVL) is a cytotoxin that causes leucocyte destruction and tissue necrosis. Although there is a strong epidemiological association of CA-MRSA infections and PVL production, its role in the pathogenesis and spread of infection is controversial. In a mouse sepsis model, PVL-negative strains of CA-MRSA were as lethal as wild-type strains and caused comparable skin disease.4 In a study of 31 strains collected from patients with infections of varying severity, the quantity of PVL production in vitro did not correlate with the severity of infection. Host factors that particularly predispose to S. aureus infection include inborn defects in neutrophil function, diabetes mellitus, and the presence of foreign material. Nasal carriers are more likely to develop nosocomial bacteraemia, though the associated mortality may be lower.
The genus Staphylococcus currently contains 35 species, all of which are part of the normal skin and mucous membrane flora of humans and animals. S. aureus is the most important pathogen, causing various pyogenic infections and toxin-mediated illnesses in normal hosts. Other species are collectively termed ‘coagulasenegative staphylococci’. These are generally considered nonpathogenic, apart from Staphylococcus epidermidis, which causes nosocomial (hospital-associated) bacteraemia and device-related infections, and Staphylococcus saprophyticus, which is a common cause of urinary tract infection. Staphylococcus aureus S. aureus is carried in the anterior nares of 20e40% of adults, depending on seasonal and local epidemiological factors. Some groups (e.g. medical staff, patients with type 1 diabetes, haemodialysis patients, intravenous drug users) appear to be particularly prone to colonization with S. aureus. Carriers transfer the organism to the skin, where trauma can provide a portal of entry, leading to local, deep, or systemic infection. The global spread of meticillin-resistant S. aureus (MRSA), which is
ME Torok MA MRCP FRCPath is a Consultant in Infectious Diseases in the Department of Infectious Diseases, Addenbrooke’s Hospital, Cambridge, UK. Competing interests: none declared.
Microbiology: S. aureus grows rapidly aerobically and anaerobically on blood agar and other non-selective solid media. Most strains are b-haemolytic. Microscopically, S. aureus is apparent as Gram-positive cocci that tend to form clusters on solid media. Identification is usually confirmed by positive catalase, coagulase and DNase tests. Typing is now
NPJ Day MA MRCP is Director of the WellcomeeMahidoleOxford Tropical Medicine Research Programme, Hospital for Tropical Diseases, Bangkok, Thailand. Competing interests: none declared.
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performed by molecular methods (e.g. pulsed-field gel electrophoresis, multi-locus sequence typing, SCCmec typing or spa typing).
Staphylococcal scalded skin syndrome is caused by epidermolytic toxin-producing S. aureus and is usually seen in children. Clinical presentation ranges from bullous impetigo to severe, generalized, exfoliative dermatitis with systemic upset. It is usually treated with intravenous antibiotics, supportive skin care and careful management of fluid and electrolyte losses. Toxic shock syndrome is caused by TSST-1 and other related staphylococcal enterotoxins. The menstrual form is associated with tampon use, the non-menstrual form with vaginal infections, contraceptive devices, abortion, childbirth and surgical procedures. The clinical case definition includes fever, hypotension, desquamating rash and involvement of three or more organ systems. Management requires aggressive fluid resuscitation, removal of any tampon, and parenteral anti-staphylococcal antibiotics.
Clinical manifestations: S. aureus is a major cause of skin and soft-tissue infections including impetigo, ecthyma (ulcerative pyoderma), folliculitis, furuncles, carbuncles, erysipelas, cellulitis and necrotizing fasciitis (see Medicine 37(11), pp. 603e609). Over the past few years, outbreaks of CA-MRSA infection have been reported in children, Alaskan natives, Pacific islanders, prisoners, sports teams and military personnel.2 CA-MRSA has become the most common cause of skin and soft-tissue infections presenting to emergency departments in the USA.5 The incidence of S. aureus bacteraemia, and the proportion of bacteraemic episodes caused by MRSA, has also increased over the past few years.6 It can be divided into two categories: community-acquired bacteraemia (onset <2 days post-hospital admission) and hospital-acquired (onset 2 days after hospital admission). Metastatic infections such as endocarditis, pericarditis, pneumonia, pulmonary abscesses, empyema, septic bursitis, septic arthritis, pyomyositis and discitis osteomyelitis can occur (Figures 1 and 2). The diagnosis is confirmed by cultures of blood and appropriate clinical specimens. Patients with S. aureus bacteraemia should have an echocardiogram to look for endocarditis. Investigations for metastatic infection should be guided by symptoms (e.g. magnetic resonance scan of spine to exclude suspected vertebral discitis or osteomyelitis).
Coagulase-negative staphylococci Coagulase-negative staphylococci (CoNS) are skin commensals. Often dismissed as culture contaminants, they are becoming increasingly recognized as pathogens.7 S. saprophyticus is a common cause of community-acquired urinary tract infection. S. epidermidis causes nosocomial bacteraemia and prosthetic device-related infections. Other species that have been associated with infection include Staphylococcus haemolyticus, Staphylococcus lugdunensis and Staphylococcus schleiferi. These organisms adhere to prosthetic material and become embedded in an exopolysaccharide matrix, forming a biofilm. The biofilm protects the organisms from phagocytic cells and reduces the penetration of antibiotics.
Management: treatment of S. aureus infections depends on the nature of the primary focus and the presence or absence of metastatic infection. Flucloxacillin is the drug of choice in meticillin-sensitive S. aureus (MSSA) infections, whereas vancomycin (or teicoplanin) is used in MRSA infections and penicillin-allergic patients. The role of the newer Gram-positive antimicrobial agents (e.g. linezolid, daptomycin, ceftobiprole) in the treatment of MRSA infections remains to be established. Aminoglycosides exhibit synergistic activity in vitro and are often used in endocarditis and other severe infections. Skin and softtissue infections usually respond to 7e14 days of antibiotic therapy. Deeper infections, such as deep abscesses, septic arthritis or osteomyelitis, often require drainage of the focus and more prolonged antimicrobial therapy. Catheter-related bacteraemia is treated with removal of the catheter and 14 days’ intravenous therapy. Bacteraemia of unknown source or endocarditis is treated with a minimum of four weeks’ intravenous therapy. The treatment of endocarditis is discussed elsewhere (see Medicine 37(11), pp. 582e585). In prosthetic device-related infection, the device should be removed and the infection treated with prolonged (4e6 weeks) intravenous therapy. In cases where the device cannot be removed (e.g. vascular graft infection), oral suppressive antimicrobial therapy should be continued indefinitely.
Microbiology: coagulase-negative staphylococci grow rapidly aerobically and anaerobically on blood agar and other nonselective solid media. Microscopically, they are Gram-positive cocci that form clusters on solid media. Identification is usually confirmed by negative coagulase and DNase tests. Nosocomial isolates usually multiply antibiotic-resistant (mainly plasmidmediated). Typing of coagulase-negative staphylococci is performed by molecular methods, because biochemical tests are unreliable. Clinical manifestations: S. saprophyticus is a common cause of cystitis in young women. It is treated with oral antibiotics (e.g. trimethoprim, nitrofurantoin or ciprofloxacin).
Toxin-mediated diseases: S. aureus can also cause a number of toxin-mediated diseases, such as food poisoning, scalded skin syndrome, and toxic shock syndrome. Staphylococcal food poisoning presents with vomiting and diarrhoea within hours of ingestion of foods containing enterotoxin-producing bacteria. Treatment is symptomatic.
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Figure 1 Psoas abscess caused by Staphylococcus aureus.
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placed taxonomically using molecular techniques such as DNA hybridization and ribosomal RNA sequencing. Group A streptococcus Group A streptococcus (Streptococcus pyogenes) is a major human pathogen, causing acute pharyngitis and variety of cutaneous and systemic infections. There are several pathogenic determinants, including M protein and a hyaluronic acid capsule, both of which are anti-phagocytic. Exotoxins (A, B, C, mitogenic factor and streptococcal superantigen), haemolysins (streptolysins O and S) and enzymes (DNases, hyaluronidase and streptokinase) are also produced.8 Microbiology: group A streptococci grow rapidly aerobically and anaerobically on blood agar and other non-selective solid media and are b-haemolytic. Microscopically, they are Grampositive cocci that grow in pairs or short chains. Identification is usually confirmed by streptococcal grouping using latex agglutination. Clinical manifestations: streptococcal pharyngitis is a common childhood infection, spread by droplet and presenting after a 2e4-day incubation period with fever, sore throat, inflamed pharynx, tonsillar enlargement, and tender regional lymphadenopathy. Treatment is with oral penicillin for 10 days. Group A streptococcus also causes various skin and soft tissue infections, including erysipelas, cellulitis and necrotizing fasciitis, which are described elsewhere (see Medicine 37(11), pp. 603e609). The incidence of severe, invasive infections appears to be increasing9 but the reason for this is not clear. Streptococcal toxic shock syndrome can be defined as any streptococcal infection associated with sudden onset of shock (systolic blood pressure 90 mm Hg) and multi-organ failure (defined as two or more of the following: renal impairment; coagulopathy; hepatic impairment; adult respiratory distress syndrome; generalized rash that may desquamate; soft-tissue necrosis). Streptococcal M protein is thought to have a major role in the pathogenesis by forming complexes with fibrinogen that bind to integrins on the surface of circulating neutrophils. The activated neutrophils cause endothelial cell damage and consequent vascular leakage and hypercoagulability, leading to hypotension and organ damage. Management is with prompt, aggressive surgical debridement of suspected deep-seated streptococcal infection, intravenous broad-spectrum antibiotic therapy, and intensive-care support. Once a streptococcal cause is confirmed, treatment can be rationalized to intravenous benzylpenicillin and clindamycin. Scarlet fever results from infection with an organism that produces an erythrogenic toxin (Figure 3). These toxins are superantigens; two (SPE A and SPE B) resemble S. aureus enterotoxins at the molecular level. A scarlatinal rash occurs, usually on the second day of the illness, and spreads from the upper chest to the trunk, neck and extremities, sparing the palms and soles. The rash fades over one week and is followed by extensive desquamation. Severe forms of disease are characterized by fever and marked systemic toxicity. Treatment is with penicillin. Acute rheumatic fever is an autoimmune disease caused by immunological cross-reactivity between streptococcal M proteins
Figure 2 L1/2 discitis caused by Staphylococcus aureus.
S. epidermidis is the most common cause of nosocomial bacteraemia and is often associated with intravascular catheters or prosthetic material. It is also the most common cause of early prosthetic-valve endocarditis (see Medicine 37(11), pp. 582e585) and cerebrospinal fluid shunt infections. Other infections include peritoneal dialysis catheter-associated peritonitis, bacteraemia in immunocompromised patients and neonates, sternal osteomyelitis, prosthetic joint infections, vascular graft infections and post-surgical endophthalmitis. Management: treatment of coagulase-negative staphylococcal infections usually requires removal of the intravascular catheter or infected prosthetic device and intravenous antibiotic therapy (e.g. vancomycin or teicoplanin). Where the foreign material cannot be removed, prolonged intravenous antibiotic therapy is required, and is often followed by long-term oral suppressive therapy.
Streptococci Streptococci are catalase-negative Gram-positive cocci that grow in pairs or chains. More than 30 species have been identified; those discussed below are the most pathogenic in humans. Classification of streptococci is complex and based on a number of features including haemolysis pattern on blood agar, biochemical reactions, antigenic composition, and genetic analysis. Three patterns of haemolysis are seen on blood agar: partial haemolysis (a-haemolysis); complete haemolysis (b-haemolysis); and non-haemolysis. a-Haemolytic streptococci produce a greenish discoloration of blood agar, hence the term ‘viridans streptococci’. b-Haemolytic streptococci are classified into Lancefield serogroups, determined by antigenic differences between cell wall carbohydrates. Streptococci lacking a recognizable group antigen are identified by their biochemical reactions, and
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and epidural and brain abscesses. Predisposing factors include defects in antibody formation, complement deficiency, neutropenia, hyposplenism, extremes of age, alcoholism, diabetes, and chronic diseases. Pathogenesis: S. pneumoniae has several adhesins that enable it to bind to epithelial cell receptors. It produces a capsule that helps it to evade phagocytosis. ‘C-polysaccharide’ (a teichoic acid constituent of the cell wall containing choline phosphate) is unique to S. pneumoniae and is responsible for the reaction between pneumococci and C-reactive protein, which leads to complement activation. Microbiology: S. pneumoniae grows in chains in liquid media, but often appears on Gram stain as lanceolate diplococci. It is ahaemolytic on blood agar, produces a negative catalase reaction, and is sensitive to optochin. Serotypes are based on antigenic differences between capsular polysaccharides. Resistance to penicillin and macrolides is increasing worldwide, ranging from 1 to 90% in different geographical areas.11 High-level penicillin resistance remains uncommon in the UK (3.8% of invasive isolates in 2007) but resistance to erythromycin is somewhat higher at 9%.12
Figure 3 The rash of scarlet fever in group A streptococcal bacteraemia.
and cardiac antigens, and is a delayed sequela of streptococcal pharyngitis. It mainly affects 6e15-year olds, particularly in the developing world. Non-suppurative inflammatory lesions involve the heart, joints, skin, subcutaneous tissues and central nervous system. Damage to the heart valves can result in progressive valvular lesions and cardiac failure. Diagnosis is based on the revised Jones criteria.10 Treatment is with analgesics and/or anti-inflammatory drugs (aspirin or corticosteroids). Post-streptococcal glomerulonephritis results from crossreactivity between streptococcal M proteins and host antigens, and follows streptococcal pharyngitis or pyoderma. It is an acute inflammatory disorder of the renal glomerulus, associated with diffuse proliferative glomerular lesions and presents with acute renal failure. Diagnosis is based on clinical features and confirmatory evidence of recent streptococcal infection. Treatment is directed towards management of acute problems (e.g. hypertension, fluid overload, acute renal failure) and eradication of the causative organism with penicillin (to prevent further transmission of the nephritogenic clone). The prognosis is good, although a few patients develop chronic glomerulonephritis.
Clinical manifestations: worldwide, S. pneumoniae is the most common cause of otitis media, community-acquired pneumonia and bacterial meningitis. It is also the predominant organism isolated in patients with meningitis following head injury. S. pneumoniae also causes sinusitis, bacteraemia, para-pneumonic effusion, empyema, lung abscess, septic arthritis, osteomyelitis, spontaneous bacterial peritonitis and endocarditis. S. pneumoniae infections are more common in HIV-infected persons and young people presenting with invasive disease should be offered an HIV test. Treatment: the treatment of S. pneumoniae infections depends on the site of infection and drug susceptibility pattern of the organism. Infections such as otitis media and sinusitis can be treated with oral amoxicillin (or moxifloxacin if the patient is penicillin-allergic). Treatment of pneumonia is with oral or intravenous amoxicillin, depending on disease severity. Alternatives in penicillin-allergic patients are doxycycline, erythromycin or clarithromycin. Bacteraemia is treated with intravenous benzylpenicillin. Meningitis is initially treated with intravenous ceftriaxone; vancomycin can be added if there is a high risk of penicillin resistance (e.g. patient from abroad). If the isolate is found to be fully susceptible (penicillin MIC <0.06 mg/L), treatment can be rationalized to benzylpenicillin. If the isolate has intermediate penicillin susceptibility (penicillin MIC 0.12e 1.0 mg/L), treatment should continue with ceftriaxone. Adjunctive corticosteroids have been recommended for the treatment of adult bacterial meningitis,13 but more recent data from the developing world are less supportive of their use.14,15
Group C and G streptococci Group C and G streptococci are b-haemolytic streptococci that colonize the nasopharynx, skin and genital tract and cause infections similar to group A streptococcus. These include pharyngitis, skin and soft-tissue infections, septic arthritis, osteomyelitis, pneumonia, endocarditis, puerperal sepsis, neonatal sepsis and bacteraemia. Post-streptococcal glomerulonephritis has been associated with group C streptococci. The treatment of choice for both group C and G streptococcal infections is penicillin (or vancomycin in penicillin-allergic patients). Penicillin tolerance is a feature of group C streptococci and synergistic gentamicin therapy has been recommended for the therapy of severe infections. Streptococcus pneumoniae S. pneumoniae (pneumococcus) is a common bacterial pathogen of humans found in the nasopharynx of 20e40% of children and 10e20% of adults. Colonization and infection rates are seasonal, increasing during the winter. S. pneumoniae is a major cause of otitis media, sinusitis, pneumonia and meningitis. Less commonly, it causes bacteraemia, peritonitis, endocarditis, pericarditis, septic arthritis, osteomyelitis, soft-tissue infections,
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Prevention: invasive disease can be prevented by vaccination. The pneumococcal polysaccharide vaccine, which contains 23 serotypes, has been recommended in those patients aged >65 years and those at increased risk (e.g. age >65 years, asplenia/hyposplenism, chronic respiratory,
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cardiac, renal or liver diseases, diabetes, immunosuppression, cochlear implants, cerebrospinal fluid leaks). In 2006, the pneumococcal conjugate vaccine, which contains seven serotypes, was added to the UK routine childhood immunization schedule. Group B streptococcus Group B streptococcus (Streptococcus agalactiae) is an important pathogen in pregnancy, post-partum women, and in neonates. The prevalence of asymptomatic vaginal colonization in pregnant women is 5e40%. The rate of vertical transmission in neonates born to women colonized at the time of delivery is 50%. The most devastating infections (bacteraemia and meningitis) occur in neonates, but group B streptococci can also cause bacteraemia in adults.
Figure 4 Purpuric rash in a patient with Streptococcus suis bacteraemia.
the oral cavity. They are considered to be of low pathogenicity, apart from their propensity to adhere to cardiac valves and cause endocarditis. Some species (e.g. Streptococcus mutans) have a strong association with dental caries. Viridans streptococci are facultatively anaerobic, catalasenegative Gram-positive cocci that grow on blood agar and other non-selective solid media, and are mainly a-haemolytic. Although some isolates react with Lancefield grouping antisera, they do not conform to specific serogroups and many isolates are non-groupable. In the past, the terminology applied to the viridans group of streptococci was confusing and inconsistent. Molecular techniques have now enabled genotypic differentiation, which has subsequently been found to correlate with phenotypic differences in biochemical tests. At present, clinically significant species can be assigned to one of the following groups: anginosus group; mitis group; mutans group; salivarius group. The viridans streptococci are a major cause of native valve endocarditis, usually in patients with underlying valve disease. They can also cause bacteraemia (particularly in neutropenic patients), meningitis, and pneumonia. Viridans streptococci were previously uniformly susceptible to penicillin but resistance to penicillin is increasing, particularly in nosocomial bloodstream isolates from immunocompromised patients. Although viridans streptococci are resistant to aminoglycosides (when traditional breakpoints are used), synergistic bactericidal activity has been seen with penicillin and aminoglycosides. Thus, a combination of penicillin and gentamicin is usually used to treat endocarditis (see Medicine 37(11), pp. 582e585).
Microbiology: group B streptococci are facultatively anaerobic, b-haemolytic diplococci that grow readily on various media. Definitive identification is based on detection of the group Bspecific cell wall antigen by latex agglutination. They can be subclassified into nine serotypes based on capsular polysaccharide determinants. Clinical features: group B streptococci are important pathogens in pregnancy and can cause asymptomatic bacteriuria, cystitis or, less often, pyelonephritis. Colonized pregnant women are at significantly increased risk of premature rupture of membranes, post-partum fever, endometritis and wound infection. Rarely, pelvic abscess, septic shock or septic thromboembolism occurs. Group B streptococci are also important causes of neonatal sepsis. Early-onset infection (onset <7 days after birth) is associated with certain maternal risk factors (age <20 years, previous miscarriage, premature or prolonged rupture of membranes, intra-partum fever) and prematurity (delivery at <37 weeks’ gestation) and presents with septicaemia (60%), pneumonia (30%) or meningitis (10%). Mortality is 2e8% in term infants and is inversely proportional to birth weight. Late-onset infection (7 dayse3 months) presents with bacteraemia, meningitis, osteomyelitis or septic arthritis. Uncommon foci include cellulitis, adenitis, otitis media, conjunctivitis, empyema, peritonitis, endocarditis and deep abscesses. Treatment is with high-dose intravenous benzylpenicillin. Invasive group B streptococcal infection causes considerable morbidity and mortality in adults. In the non-pregnant population, the incidence increases with age; men are more commonly affected. Diabetes, liver disease, neurological conditions, malignancy, renal or urological disease, cardiopulmonary disease and HIV infection predispose to invasive infection. Bacteraemia is the most common presentation. Other syndromes include pneumonia, septic arthritis, osteomyelitis, skin and softtissue infections, and meningitis. Treatment of adult infection is with high-dose intravenous benzylpenicillin (or vancomycin in those allergic to penicillin). Mortality in non-pregnant adults is 21e32%.
Streptococcus bovis S. bovis causes endocarditis and bacteraemia, the latter often associated with colonic malignancy or hepatic cirrhosis. It is an a-haemolytic streptococcus and is identified by biochemical tests and Lancefield serogrouping (group D). It is highly susceptible to penicillin, which is the drug of choice. Streptococcus suis S. suis was previously considered to be predominantly an animal pathogen but is increasingly being recognized as a cause of bacterial meningitis and septicaemia in humans (Figure 4).16 In 2005, a large outbreak of 215 cases occurred in China associated with a high mortality rate (62%).17 Predisposing factors include contact with pigs or undercooked pork, alcoholism and splenectomy. The organism is a-haemolytic and is identified by biochemical tests and serotyping. Treatment is with benzylpenicillin. A
Viridans streptococci Viridans streptococci are commensals in the gastrointestinal, respiratory and female genital tracts and are most prevalent in
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REFERENCES 1 Boucher HW, Corey GR. Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008; 46: S344e9. 2 Weber JT. Community-associated methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2005; 41: S269e72. 3 Appelbaum PC. Reduced glycopeptide susceptibility in methicillinresistant Staphylococcus aureus (MRSA). Int J Antimicrob Agents 2007; 30: 398e408. 4 Diep BA, Otto M. The role of virulence determinants in community-associated MRSA pathogenesis. Trends Microbiol 2008; 16: 361e9. 5 King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med 2006; 144: 309e17. 6 Johnson AP, Pearson A, Duckworth G. Surveillance and epidemiology of MRSA bacteraemia in the UK. J Antimicrob Chemother 2005; 56: 455e62. 7 Rogers KL, Fey PD, Rupp ME. Coagulase-negative staphylococcal infections. Infect Dis Clin North Am 2009; 23: 73e98. 8 Bisno AL, Brito MO, Collins CM. Molecular basis of group A streptococcal virulence. Lancet Infect Dis 2003; 3: 191e200. 9 Lamagni TL, Darenberg J, Luca-Harari B, et al. Epidemiology of severe Streptococcus pyogenes disease in Europe. J Clin Microbiol 2008; 46: 2359e67. 10 Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. Special writing group of the committee on rheumatic fever, endocarditis, and Kawasaki disease of the council on cardiovascular disease in the young of the American Heart Association. JAMA 1992; 268: 2069e73.
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11 Van Bambeke F, Reinert RR, Appelbaum PC, Tulkens PM, Peetermans WE. Multidrug-resistant Streptococcus pneumoniae infections: current and future therapeutic options. Drugs 2007; 67: 2355e82. 12 Health Protection Agency. Antimicrobial resistance and prescribing in England. Wales and Northern Ireland: Health Protection Agency, 2008. 13 de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347: 1549e56. 14 Scarborough M, Gordon SB, Whitty CJ, et al. Corticosteroids for bacterial meningitis in adults in sub-Saharan Africa. N Engl J Med 2007; 357: 2441e50. 15 Nguyen TH, Tran TH, Thwaites G, et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med 2007; 357: 2431e40. 16 Wertheim HF, Nghia HD, Taylor W, Schultsz C. Streptococcus suis: an emerging human pathogen. Clin Infect Dis 2009; 48: 617e25. 17 Yu H, Jing H, Chen Z, et al. Human Streptococcus suis outbreak, Sichuan, China. Emerg Infect Dis 2006; 12: 914e20.
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Staphylococci and streptococci are commensal organisms that can cause a wide variety of conditions ranging from skin and soft tissue infections to severe, life-threatening infections Patients who are systemically unwell should be admitted for appropriate investigations and intravenous antibiotic therapy Drug-resistance in these organisms is increasing and empirical antimicrobial therapy may need to reflect this
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