++
In its beginning the malady is easier to cure but difficult to detect, but later it becomes easy to detect but difficult to cure.
NICCOLÒ MACHIAVELLI (1469–1527), ON TUBERCULOSIS
++
Bacterial infections can present diagnostic brain-teasers, and a high index of suspicion is needed to pinpoint the diagnosis. Many are rarely encountered, thus making diagnosis more difficult yet demanding vigilance and clinical flexibility.
++
++
tuberculosis
infective endocarditis
syphilis
septicaemia
the zoonoses (e.g. brucellosis, Lyme disease)
clostridial infections: tetanus, gas gangrene, puerperal infection, botulism, pseudomembranous colitis
hidden suppuration: abscess, osteomyelitis
mycoplasma infections: atypical pneumonia
Chlamydia infections: psittacosis, non-specific arthritis, pelvic inflammatory disease, trachoma, atypical pneumonia
legionnaire disease
Hansen disease
++
Chlamydia and rickettsial organisms have been confirmed as being small bacterial organisms.
++
Tuberculosis (TB), caused by Mycobacterium tuberculosis, still has a worldwide distribution with a very high prevalence in Asian countries where 60–80% of children below the age of 14 years are affected.1 This has special implication in Australia, where large numbers of Asian migrants are settling. The WHO estimates that one-third of the world’s population is infected by the tubercle bacillus. It remains a deadly disease with about 2 million people worldwide dying of TB every year and 8 million new cases a year.
++
TB can be a mimic of other diseases and a high level of suspicion is necessary to consider the diagnosis, especially if there are only extrapulmonary manifestations. There may be no symptoms or signs, even in advanced disease. Ideally patients should be referred early for specialist management.
+++
High risk people/situations
++
newborn and infants
adults over 60 years
patients with HIV/AIDS
chronic disease, e.g. diabetes
crowded or unsanitary living conditions
people affected by alcohol and drugs
immigrants and refugees from endemic countries (especially Indian sub-continent, Papua New guinea, South East Asia, Sub Sahara and South Africa)
++
DxT malaise + cough + weight loss ± fever/night sweats + haemoptysis ➜ pulmonary TB
++
The primary infection usually involves the lungs. Transmission is by droplet infection. The focus is usually subpleural in the upper to mid zones and is almost always accompanied by lymph node involvement.
++
Erythema nodosum may accompany the primary infection (see FIG. 29.1). Primary TB is symptomless in most cases although there may be a vague, ‘not feeling well’ illness associated with a cough. In most people this pulmonary focus heals but leaves some surviving tubercle bacilli, even if it becomes calcified (the Ghon focus).
++
+++
Progressive primary tuberculosis
++
If the immune response is inadequate, progressive primary TB develops, with constitutional and pulmonary symptoms. Rarely, haematogenous spread can occur to the lungs (‘miliary tuberculosis’), to the pleural space (tuberculosis pleural effusion) or to extrapulmonary sites such as the meninges and bone.
+++
Latent TB infection (LTBI)
++
LTBI is the presence of infection without evidence of active disease (contained by the immune system) and inability to transmit the infection. However, reactivation may occur if the host’s immune defences are impaired (occurs in about 10%). LTBI is very common in children in and from developing countries. Consider HIV in these people. The tubercular skin test is primarily intended to identify these people with a view to prophylaxis therapy. The standard preferred regimen is isoniazid (10 mg/kg up to 300 mg (o) daily for 6–9 months). This decision should be made by a consultant.
+++
Post-primary or adult-type pulmonary TB
++
Most cases of TB in adults are due to reactivation of disease some years later and not to re-infection. Symptoms of active TB include persistent cough, sputum production, haemoptysis, fever, sweating, malaise, weight loss and anorexia. The factors causing this include poor social living conditions with malnutrition, diabetes and other factors lowering natural immunity, such as immunosuppressant drugs, corticosteroids, lymphoma and HIV infection (later stage). The chest X-ray is usually abnormal—classic apical disease with infiltration and cavitation with fibrotic changes.
++
Practice tip
TB! − Think HIV.
+++
Reactivated pulmonary TB
++
This usually presents with constitutional symptoms of poor health and night sweats, and a cough that is initially dry but may become productive and be bloodstained (see CHAPTER 42). Sometimes the infection will be asymptomatic. The natural history of TB is illustrated in FIGURE 29.2.
++
++
The main sites of extrapulmonary disease (in order of frequency in Australia) are the lymph nodes (the commonest, especially in young adults and children), genitourinary tract (kidney, epididymis, Fallopian tubes), pleura and pericardium, the skeletal system (arthritis and osteomyelitis with cold abscess formation), CNS (meningitis and tuberculomas), the eye (choroiditis, iridocyclitis), the skin (lupus vulgaris), the adrenal glands (Addison disease—see CHAPTER 23) and the GIT (ileocaecal area and peritoneum). This is increasing, especially in HIV patients.
++
These sites are illustrated in FIGURE 29.3.
++
++
This disorder follows diffuse dissemination of tubercle bacilli via the bloodstream especially in those with chronic disease and immunosuppression. It can occur within 3 years of the primary infection or much later because of reactivation.
++
The symptoms, which are insidious, include weight loss, fever and malaise. Choroidal tubercules are pathognomonic. The classic chest X-ray is multiple 1–2 mm nodules in lung fields. It is fatal without treatment.
++
Children living in close contact with people with smear-positive pulmonary TB are highly vulnerable to acquiring the primary infection. A possible complication is miliary TB. The lifetime risk of TB disease in children with LTBI is in the order of 5–15%.4 Children with LTBI should be considered for prophylaxis with a course of isoniazid.
++
Primary disease is the more common form in young children. Reactivation is more common in adolescents.
++
A high index of suspicion is critical for the diagnosis of TB. Tests include:
++
Mantoux tuberculin test (TST) (a guide only)
chest X-ray; CT scan if doubtful
sputum or bronchial excretion or gastric aspirates for stain (acid-fast bacilli) and culture (takes about 6–8 weeks but important). Ideally requires 3 specimens over 3 days including one early morning
immunochromatographic finger-prick test (new and promising)
interferon gamma release assay (IGRA)
NAAT/PCR test—less sensitive than culture
biopsies on lesions/lymph nodes may be necessary. The hallmark is caseating granulomata
fibre-optic bronchoscopy to obtain sputum may be necessary
consider HIV studies
+++
Tuberculin (Mantoux) testing and BCG vaccination
++
A tuberculin (Mantoux) test should be performed prior to BCG vaccination in all individuals over 6 months of age. (It is read at 48–72 hours.) It is not a good test to diagnose TB.
++
++
<5 mm—negative (note: may be negative in presence of very active pulmonary infection)
5–10 mm—typical of past BCG vaccination
>5 mm—significant in immunocompromised, close contacts and HIV infection
>10 mm—positive = tuberculosis infection (active or inactive)
>15 mm—highly significant for ‘normal’ people
++
The BCG vaccination should be given if the reaction is <5 mm induration. Do not give it for a reaction >5 mm.
++
BCG vaccination is recommended for:
++
ATSI neonates in regions of high incidence
neonates born to patients with leprosy or family history of leprosy
children <5 years travelling for long periods to countries of high TB prevalence
++
BCG vaccination should be considered for:
++
neonates in household with immigrants or visitors recently arrived from countries of high prevalence (e.g. South-East Asia) (note: tuberculin test not necessary for neonates <14 days)
children and adolescents <16 years with continued exposure to active TB patient and where isoniazid therapy is contraindicated
others at increased risk (and where value of BCG vaccine uncertain), such as health care workers, travellers >5 years with significant exposure
++
BCG vaccination is contraindicated for:
++
tuberculin reactions >5 mm
immunocompromised or malignancies involving bone marrow lymphatics (can disseminate infection)
high-risk HIV infection
significant fever or intercurrent illness
generalised skin diseases, including keloid tendency
pregnancy
previous infection
++
This includes the increasing emergence of forms resistant to two or more front-line drugs—multidrug-resistant TB (MDR-TB). TB is much more aggressive in the immunocompromised and if not adequately treated can be fatal in 2 months, especially if they have MDR-TB. Treatment compliance is a huge issue and so the directly observed therapy (DOT) strategy for isoniazid in children is a WHO priority, as is ‘DOTS plus’ to control MDR-TB. TB is a more pressing problem in children requiring early treatment.
+++
Management and treatment5,6
++
Referral to experienced specialist care is appropriate. The current antimicrobial treatment is to use four antituberculous drugs initially (rifampicin + isoniazid + pyrazinamide + ethambutol) daily for 2 months, then rifampicin + isoniazid daily for a further 4 months. The usual precautions with adverse reactions are required. Pyridoxine 25 mg daily is recommended for adults taking isoniazid. A 3-times-weekly regimen is also an option if DOT is employed. Corticosteroids may be prescribed. Notify appropriate jurisdictional public health authorities. Promote healthy lifestyle advice.
++
Although syphilis is uncommon, it is increasing in the general population. It is extremely common in certain Indigenous groups and is frequently acquired from sexual contacts overseas.5,8
++
It presents either as a primary lesion or through the chance finding of positive syphilis serology. Family physicians should be alert to the various manifestations of secondary syphilis, which can cause difficulties in diagnosis. Congenital syphilis is rare where there is general serological screening of antenatal patients. Early syphilis—less than 2 years duration and based on positive serology—includes primary, secondary and latent syphilis.
++
The primary lesion or chancre usually develops at the point of inoculation after an incubation period averaging 21 days. The chancre is typically firm, painless, punched out and clean (see FIG 29.4). The adjacent lymph nodes are discretely enlarged, firm and non-suppurating. Any anorectal ulcer or sore should be considered as syphilis until proved otherwise.
++
++
Untreated, early clinical syphilis usually resolves spontaneously within 4 weeks, leading to latent disease, which may proceed to late destructive lesions.
++
The interval between the appearance of the primary chancre and the onset of secondary manifestations varies from 6 to 12 weeks after infection. Constitutional symptoms, including fever, headache, malaise and general aches and pains, may precede or accompany the signs of secondary syphilis.
++
The most common feature of the secondary stage of infection is a rash, which is present in about 80% of cases. The rash is typically a symmetrical, generalised, coppery-red maculopapular eruption on the face, trunk, palms and soles and is neither itchy nor tender. It can resemble any skin disease except those characterised by vesicles.
++
Positive serology in a patient without symptoms or signs of disease is referred to as latent syphilis and is the commonest presentation of syphilis in Australia today. Possibly because of the widespread use of antibiotics, the infection often proceeds to the latent stage without a recognised primary or secondary stage.
+++
Late (tertiary) syphilis
++
Tertiary manifestation of syphilis (follows >2 years latency), which is very rare, may be ‘benign’ with development of gummas (granulomatous lesions) in almost any organ, or more serious with cardiovascular or CNS involvement. Benign gummatous disease is rare but cardiovascular disease and neurosyphilis occasionally occur. Careful management and follow-up of patients with early or latent disease is essential to prevent late sequelae. It can only be detected by blood tests.
++
++
meningovascular (e.g. cranial nerve palsies)
tabes dorsalis (e.g. sensory ataxia, lightning pains, Charcot joints)
general paresis of the insane (e.g. dementia, psychosis)
++
Syphilis should not be overlooked as a cause of oral, ocular or anorectal lesions. The diagnosis of syphilis depends on a detailed history, careful clinical examination and specific examinations.
++
Underlying these approaches is the need to think of the possibility of syphilis with concurrent STIs.
+++
Syphilis and HIV infection8
++
HIV and syphilis are commonly associated. In patients with AIDS and syphilis, standard regimens for syphilis are not always curative. Seronegative syphilis has been reported in patients with HIV infection. Lymphadenopathy in a patient with HIV infection may be due to coexisting secondary syphilis.
+++
Dark field examination7
++
Spirochaetes can be demonstrated by microscopic examination of smears from early lesions using dark field techniques and provide an immediate diagnosis in symptomatic syphilis. The direct fluorescent antibody techniques (FTAABS) can be used on this smear.
++
Serological tests provide indirect evidence of infection, and the diagnosis of asymptomatic syphilis relies heavily on these tests. The main types of tests are:
++
reagin tests (VDRL and RPR)—not specific for syphilis but useful for screening
treponemal tests (TPPA, TPI, EIA, FTA-abs)—specific tests, with the latter being sensitive and widely used
PCR (blood or CSF)—very sensitive
++
+++
Infective endocarditis
++
Infective endocarditis, although uncommon, has high morbidity and mortality. It can be a difficult problem to diagnose but must be considered in the differential diagnosis of fever, especially in patients with a history of cardiac valvular disorders. It is caused by microbial infection of the cardiac valves or endocardium. Previously referred to as bacterial endocarditis, the term infective endocarditis is preferred because not all the infecting organisms are bacteria.
++
It may present as a fulminating or acute infection but more commonly runs an insidious course and is referred to as subacute (bacterial) endocarditis. Its incidence is increasing, probably due to the increasing number of elderly people with degenerative valve disease, more invasive procedures, IV drug use and increased cardiac catheterisation.9
++
DxT FUO + cardiac murmur + embolism ➜ endocarditis
++
Past history of endocarditis
Rheumatically abnormal valves, especially ASTIP
Congenitally abnormal valves
Mitral valve prolapse
Calcified aortic valve
Congenital cardiac defects (e.g. VSD, PDA)
Prosthetic valves, shunts, conduits
IV drug use
Central venous catheters
Temporary pacemaker electrode catheters
++
Note: Only about 50% of patients with infective endocarditis have previously known heart disease.7
+++
Responsible organisms10
++
Streptococcus viridans (50% of cases) most susceptible to penicillin
Streptococcus bovis
Enterococcus faecalis
Staphylococcus aureus (causes 50% of acute form)
Candida albicans/Aspergillus (IV drug users)
Staphylococcus epidermidis
Coxiella burnetii (Q fever)
HACEK group (Gram –ve bacilli) (5–10% of cases)
++
Acute endocarditis
Subacute endocarditis
Prosthetic endocarditis
++
Infective endocarditis without cardiac murmur is frequently seen in IV drug users who develop infection on the tricuspid valve.
+++
Warning signs for development of endocarditis
++
Change in character of heart murmur
Development of a new murmur
Unexplained fever and cardiac murmur = infective endocarditis (until proved otherwise)
A febrile illness developing after instrumentation (e.g. urethral dilatation) or minor and major surgical procedures (e.g. dental extraction, tonsillectomy, abortion)
++
The ‘classic tetrad’ of clinical features:9 signs of infection, signs of heart disease, signs of embolism, immunological phenomena
++
There is a significant high mortality and morbidity from infective endocarditis, which is often related to a delay in diagnosis.
++
A golden rule
Culture the blood of every patient who has a fever and a heart murmur.
++
The classic clinical features are summarised in FIGURE 29.5.
++
++
The patients are often elderly, appear pale and ill, with intermittent fever, and complain of vague aches and pains. The full clinical presentation takes time to develop. A febrile illness of 1 to 2 weeks duration is a common presentation.
++
++
FBE and ESR: ESR ↑, anaemia and leukocytosis
urine: proteinuria and microscopic haematuria
blood culture: positive in about 75%7 (at least 3 sets of samples—aerobic and anaerobic culture)
echocardiography—to visualise vegetations (TOE more sensitive than TTE)
chest X-ray
ECG
++
Consider kidney function tests and C-reactive protein.
++
The patient should be referred because optimal management requires close cooperation between physician, microbiologist and cardiac surgeon.
++
Any underlying infection should be treated (e.g. drainage of dental abscess). Bactericidal antibiotics are chosen on the basis of the results of the blood culture and antibiotic sensitivities. Four blood cultures should be sent to the laboratory within the first hour of admission and treatment should seldom be delayed longer than 24 hours.
+++
Antimicrobial treatment10,11
++
Consultation with an infectious diseases physician or clinical microbiologist should be sought.
+++
Empirical treatment11
++
Once cultures have been taken, prompt empirical antimicrobial treatment should be commenced, especially in fulminating infection suspected to be endocarditis (usually due to Staphylococcus aureus). Benzylpenicillin, gentamicin and flucloxacillin/dicloxacillin are recommended, for example (adults):
++
benzylpenicillin 1.8 g IV, 4 hourly
plus
flucloxacillin/dicloxacillin 2 g IV, 4 hourly
plus
gentamicin 4–6 mg/kg IV, daily
Vancomycin is indicated in certain circumstances
++
For specific organisms isolated on culture and prosthetic valve endocarditis confer with a consultant.
+++
Antibiotic prophylaxis10,11
++
The evidence for prophylaxis of endocarditis is not clear, and current international practice is not to treat low-risk cardiac abnormalities having procedures with a low incidence of bacteraemia.
++
It is advisable to discuss the relative risks with patients.
++
If in doubt, discuss the issue with the patient’s cardiologist or an infectious diseases specialist.8,10
++
References for specific conditions: see References5,12 and see also http://circ.ahajournals.org (Paediatrics).
++
These include patients with murmurs not due to valve disorders, isolated secundum ASD, pacemakers, implanted defibrillators, previous rheumatic fever without valve dysfunction, previous CABGS, mitral valve prolapse without regurgitation, complete surgical or device closures of congenital heart defects.
++
No prophylaxis is recommended in these patients.
+++
High risk of adverse outcomes11
++
These include past history of endocarditis, prosthetic heart valves, most congenital heart disease especially cyanotic types and those with repaired defects, hypertrophic cardiomyopathy, cardiac transplantation recipients who develop cardiac valvulopathy, rheumatic heart disease in Indigenous patients, all acquired valvular heart disease, mitral valve prolapse with regurgitation and surgically fashioned systemic-pulmonary shunts.
+++
Procedures requiring prophylaxis11
++
Dental: invasive dental surgery—any procedure causing bleeding from gingiva, bone or mucosa, for example, dental extractions, drainage of abscess, osteotomies, dental implants, replanting avulsed teeth, periodontal procedures including probing, endodontic surgery, intraligamentary local anaesthetic injections, root canal work
Other procedures—examples are:
– genitourinary procedures in the presence of infection, for example, D&C, IUCD, urethral dilatation, circumcision, prostatic surgery, vaginal delivery in presence of infection or prolonged labour
– gastrointestinal tract procedures in presence of infection
– respiratory tract procedures—tonsillectomy/adenoidectomy, rigid bronchoscopy, nasal and sinus surgery
– incision and drainage of local abscess, for example, boils, perirectal, dacryocystitis
+++
Recommended antibiotics
++
Dental procedures and URT interventions (S. viridans and Streptococcus cover):11
++
phenoxymethylpenicillin 2 g (child 40 mg/kg up to 2 g) orally 1 hour before procedure
or
amoxycillin 2 g (child 50 mg/kg up to adult dose) orally 30 minutes beforehand (if not on long-term penicillin)
or
amoxy/ampicillin 2 g (50 mg/kg up to adult dose) IV just before procedure commences or IM 30 minutes before if having a general anaesthetic
or
if hypersensitive to penicillin: clindamycin or lincomycin
+++
Genitourinary and gastrointestinal procedures11
++
++
++
If hypersensitive to penicillin: vancomycin or teicoplanin plus gentamicin.