Antimicrobial Chemotherapy, 5th Edition
Part 4 - Therapeutic Use of Antimicrobial Agents
Bone and Joint Infections
Bacteria can infect joints via the bloodstream (haematogenous septic arthritis) from a distant focus of infection such as a septic skin lesion, otitis media, pneumonia, meningitis, gonorrhoea, or an infection of the urinary tract. However, in adults prosthetic joint infection is now by far the most common presentation. Rarely bacteria may be introduced directly into the synovial space following a penetrating wound or an intra-articular injection. Also, the joint may become infected by direct spread from an adjacent area of osteomyelitis or cellulitis. Once established, septic arthritis can give rise to secondary bacteraemia.
Haematogenous septic arthritis
Staphylococcus aureus accounts for most bacteriologically proven joint infections. Other bacteria are important in specific age groups.Escherichia coli and streptococci of Lancefield group B (Streptococcus agalactiae) occur in neonates. Pneumococci, Str. pyogenes, and coliform bacilli are found in elderly people. Haemophilus influenzae of serotype b cause septicaemia and pyogenic arthritis in children under the age of 6 but childhood immunization with the H. influenzae conjugate vaccine has markedly reduced the incidence of this infection.Neisseria gonorrhoeae occasionally causes septic arthritis in young adults. Patients with meningococcal infection may develop septic arthritis during the course of their illness. Other rare causes include Mycobacterium tuberculosis, opportunist mycobacteria, Brucella spp., fungi, andBorrelia burgdorferi, the spirochaete that causes Lyme disease.
Prosthetic joint infection
Acute infections (within 1 year of the primary operation) are often caused by Staph. aureus or Str. pyogenes. Infections occurring more than a year after surgery are caused by a much wider range of bacteria, including coagulase negative staphylococci, enterococci, aerobic Gram-negative bacilli and anaerobic bacteria.
Haematogenous septic arthritis
In nine cases out of 10 a single joint is involved, most commonly the knee, followed by the hip. Typically, the patient is a child with a high temperature and a red, hot, swollen joint with restricted movement. However, septic arthritis is not uncommon in elderly and debilitated people, who may have non-specific symptoms. Patients with rheumatoid arthritis have an increased incidence of septic arthritis and a poorer prognosis, which may in part be attributable to delay in making the clinical diagnosis.
A presumptive diagnosis rests on the immediate examination of the joint fluid, because of the difficulty on clinical grounds in distinguishing other conditions with similar features, such as an exacerbation of rheumatoid arthritis, gout, acute rheumatic fever, or trauma to the joint. Typically, the fluid is cloudy or purulent with a marked excess of neutrophils. The Gram film is of immediate help not only in confirming the diagnosis but also in the choice of the most appropriate antimicrobial therapy (Table 24.1). Despite the microscopic evidence of bacterial infection, culture of synovial fluid may sometimes fail to yield the pathogen, and blood cultures should always be taken at the same time. In suspected gonococcal arthritis, cervical, urethral, rectal, and throat swabs should also be taken for culture before starting antimicrobial therapy.
In young adults who present with acute mono-arthritis but do not have purulent joint fluid a diagnosis of reactive arthritis secondary to sexually transmitted disease should be suspected (Chapter 29).
It is very important that a diagnosis is made rapidly and appropriate therapy started immediately, because permanent damage to the joint may occur and lead to long-term residual abnormalities. Most patients who are treated promptly recover completely. Infection of the hip joint is more difficult to treat since, in addition to antibiotics, open surgical drainage is needed because of the technical difficulty of needle aspiration. The key to success is a combination of antibiotics and drainage. In most cases this is achieved by multidisciplinary management, including input from orthopaedic surgeons, medical microbiologists, and physicians. Surgeons in particular should determine whether drainage of pus should be by repeated needle aspiration or wash-out of the joint in an operating theatre.
The choice of initial antibiotic therapy depends on the age of the patient and the findings in the Gram-film. If organisms can be identified with reasonable confidence before culture, the appropriate antibiotic for that particular organism is the automatic choice irrespective of the age (Table 24.1). If bacteria are not seen at this stage, the initial choice is influenced by the age of the patient or the underlying disease. Antibiotics are chosen to cover the most likely bacterial causes of the infection (Table 24.2) and can be modified subsequently if a pathogen is isolated.
Table 24.1 Initial antimicrobial therapy in septic arthritis when bacteria are seen in the Gram-film of the joint aspirate
Most antimicrobial agents given parenterally achieve therapeutic levels in the infected joint, so the intra-articular injection of antibiotics is not recommended, particularly as it may induce chemical synovitis.
A sequential intravenous-oral regimen, carefully monitored at the time of oral therapy, is widely used. In all cases, the initial treatment must be with parenteral antibiotics until the condition of the patient has stabilized (usually 7-10 days) and the joint is reasonably dry. Switch to oral therapy is appropriate once the condition has stabilized as all of the first choice drugs are well absorbed after oral administration. The total duration of treatment is usually between 4 and 8 weeks and should be determined by clinicians who are experienced in management of these infections.
Prosthetic joint infection
Most patients with prosthetic joint infection are not systemically unwell. Infection should be suspected in any patient who develops pain or signs of local inflammation in the joint, although it is impossible to distinguish between mechanical loosening of the joint and infection unless there are obvious signs of infection such as purulent discharge from a sinus.
Because there is rarely systemic illness it is not necessary to start empirical treatment and the chances of establishing a definitive microbiological diagnosis are greatly enhanced if antibiotics are not given. Serious systemic illness is the only reason for giving empirical antibiotics, as it is extremely unlikely that prosthetic joint infection will resolve with antibiotic therapy alone.
Table 24.2 Initial antimicrobial therapy in septic arthritis when no organisms are seen in the Gram-film of the joint aspirate
Patients with suspected prosthetic joint infection should be referred urgently to an orthopaedic surgeon who specializes in revision surgery for prosthetic joints and who is likely to work closely with medical microbiologists and infectious diseases physicians.
Osteomyelitis is infection of bone and is usually caused by bacteria. Unlike soft tissues, bone is a rigid structure and cannot swell. As infection proceeds and pus forms, there is a marked rise of pressure in the affected part of the bone, which, if unchecked or unrelieved, may impair the blood supply to a wide area and result in areas of infected dead bone. Once this chronic phase of osteomyelitis is established, necrotic bone (sequestrum) must be removed surgically in addition to the use of antibiotics if the infection is to be eradicated.
Pathogenesis and aetiology
Osteomyelitis may be haematogenous (infected through the bloodstream) or non-haematogenous (infected directly through a wound, including a fracture or an overlying chronic ulcer).
This type of infection is most commonly caused by staphylococci that reach the site through the bloodstream, usually with no obvious primary focus of infection. Acute haematogenous osteomyelitis is principally a disease of children under 16 years, in whom more than 85% of cases occur. The usual sites are the long bones (femur, tibia, humerus) near the metaphysis, where the blood supply to the bone is most dense. However, when the disease occurs in adults, the vertebrae are commonly affected.
Staph. aureus accounts for about half of all cases and for more than 90% of cases in otherwise normal children. In the elderly with underlying malignancies and other diseases, and in drug addicts, Gram-negative bacilli (coliform bacilli and Ps. aeruginosa) are reported with increasing frequency. Coliforms are particularly likely to cause vertebral osteomyelitis, as it is associated with recurrent urinary tract infection. H. influenzae has become very rare since the introduction of the conjugate vaccine. Other rare causes of haematogenous osteomyelitis include M. tuberculosis, Brucella abortus, and, particularly in parts of the world where sickle-cell anaemia is prevalent, salmonellae.
When bones are infected by the introduction of organisms through traumatic or postoperative wounds, Staph. aureus is still the commonest cause, but Gram-negative bacteria may also be found. Ps. aeruginosa may occasionally produce osteomyelitis of the metatarsals or calcaneum following a puncture wound of the sole of the foot and Pasteurella multocida infection may follow animal bites. Patients with infected pressure sores over a bone, or those with peripheral vascular disease or diabetes mellitus, may develop osteomyelitis with mixed aerobic and anaerobic organisms (coliforms and Bacteroides species), although Staph. aureus is an important cause of osteomyelitis by this route also.
Clinical and diagnostic considerations
The typical manifestations of acute, haematogenous osteomyelitis include the abrupt onset of high fever and systemic toxicity, with marked redness, pain, and swelling over the bone involved. In vertebral osteomyelitis, there may be general malaise, with or without low-grade fever and low back pain. If the infection is not controlled, it may spread to produce a spinal epidural abscess, with consequent neurological symptoms.
The diagnosis of osteomyelitis is confirmed by bone biopsy. A bone scan may help to localize the site and extent of the infection. However, bone scan is simply a demonstration of increased blood supply to the affected area and cannot distinguish between infection and other causes of inflammation. A positive bone scan should be a stimulus to further investigation, whereas a negative bone scan makes the diagnosis of osteomyelitis unlikely. Magnetic resonance imaging provides additional information about the presence and location of a sequestrum. Blood cultures should be taken in addition to bone biopsy. In patients with chronic osteomyelitis, it may be misleading to base antibiotic treatment on the results of cultures of pus obtained from a draining sinus, which will often yield organisms that are secondarily colonizing the sinus. For precise bacteriological diagnosis, material must be obtained during the surgical removal of dead bone and tissue.
Guidelines for antibiotic therapy and management
It is generally agreed that acute haematogenous osteomyelitis can be cured without surgical intervention, provided antibiotics are given while the bone retains its blood supply and before extensive necrosis has occurred. In practice, this is within the first 72 h of the development of symptoms. Antibiotic therapy must, therefore, start immediately after a bone biopsy and blood cultures have been obtained. Results from a Gram-film of aspirated material may help in the initial choice of antibiotic. If no organisms are seen Staph. aureus is the prime suspect in any age group, and an antistaphylococcal agent should be used (flucloxacillin or clindamycin). If Gram-negative bacteria are isolated a fluoroquinolone is the drug of choice.
To ensure adequate concentration at the site of infection, high doses of antibiotics should be given parenterally. If an abscess has already formed when the patient is first seen, or there is no significant clinical improvement within 24 h of starting parenteral therapy, then surgical drainage of the abscess is essential.
The details of treatment, including duration of intravenous therapy and total duration of treatment should be determined by specialists with experience in the management of these complex conditions.