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Inhibitors of cell wall synthesis
https://t.me/med1917
fig
9.4
, p
379
See
selective target for antibiotics. Antibiotics which act on the cell wall include:
• - lactam antibiotics
• others: glycopeptides, polymyxins.
. The bacterial cell wall is unique in nature and therefore acts as a
- lactams: penicillins, cephalosporins, carbapenems, monobactam
Contain a - lactam ring which inhibits the formation of peptidoglycan cross- links
in the bacterial cell wall. Resistance occurs when the bacteria (eg staphylococci)
produce a - lactamase enzyme.
Penicillins: see table
9.3
, p
382
. Include natural penicillins (penicillin G and V) and
synthetic penicillins which are chemically modified to extend their spectrum of activity, eg amoxicillin, piperacillin.
In an attempt to overcome - lactamase resistance, penicillins have been combined
with - lactamase inhibitors to create - lactam- - lactamase inhibitor combinations
eg co- amoxiclav (amoxicillin + clavulanic acid), Tazocin
Staphylococcal resistance is conventionally defined by stability to meticillin, an
acid- labile and
Cephalosporins: see table
IV- only equivalent of flucloxacillin (see MRSA, p
9.4
, p
382
. Contain a - lactam ring attached to a six-
®
(piperacillin + tazobactam).
384
).
membered nuclear structure (five in penicillin), which allows synthetic modification at two sites (one in penicillin). This means that cephalosporins are the largest
groups of available antibiotics. Classification into ‘generations’ is not standardized: as a rough rule, the higher the generation, the wider the spectrum.
Carbapenems: see table
Seek expert microbiology advice before use.
Monobactam: aztreonam is only active against Gram- negative species including
Neisseria meningitidis, Haemophilus influenzae, Pseudomonas. Given
Inhaled preparation for chronic pulmonary Pseudomonas (cystic fibrosis). Dose
adjust for renal function.
9.5
, p
382
. Broadest spectrum of all - lactam antibiotics.
IV/ IM.
SE: N&V, GI bleed, rash, LFTS, plts, paraesthesia, seiz-
ures, bronchospasm.
Non- - lactam cell wall inhibitors
See fig
9.4
, p
379
, and table
9.6
, p
382
. Glycopeptides, eg vancomycin, teicoplanin.
Polymyxins, eg colistin. Fosfomycin (inhibits first step in cell wall synthesis).
Inhibitors of protein synthesis
fig
9.4
, p
379
See
• aminoglycosides
• macrolides
• tetracyclines and derivatives of tetracycline
• others: clindamycin, linezolid, chloramphenicol, fusidic acid.
, and table
9.7
, p
383
. Includes:
Inhibitors of nucleic acid synthesis
fig
9.4
, p
379
See
• folate synthesis inhibitors: trimethoprim, co- trimoxazole
• fluoroquinolones
• others: metronidazole, rifampicin, fidaxomicin.
, and table
9.8
, p
383
. Includes:
Nitrofurantoin is unique. Metabolites interfere with cell growth via ribosomes,
DNA, RNA, and cell wall. Multiple sites of attack mean resistance. Concentrates in
the urine (but not if
GFR), used in uncomplicated UTI, not systemically active. SE:
haemolysis, pulmonary fibrosis, hepatotoxicity.
Antibiotics for TB, see pp
390– 1
.
381
9 Infectious diseases
9 Infectious diseases
Antibiotics: summary tables
https://t.me/med1917
382
Table 9.
3
Penicillins
Antibiotic
Benzylpenicillin
(penicillin
‘penicillin’)
Phenoxymethyl-
penicillin
(penicillin
Ampicillin/
amoxicillin
Amoxicillin +
clavulanic acid
(co- amoxiclav)
Piperacillin +
tazobactam
Indications Considerations
Gram + ve: streptococci (chest, throat,
endocarditis, cellulitis), meningococcus,
G,
diphtheria, anthrax, leptospirosis
Throat, prophylaxis: splenectomy/
hyposplenism, rheumatic fever
V
)
Extended penicillin spectrum includes
enterobacteria ( activity against
Gram + ve): sinusitis, chest, otitis
media,
Used if resistance to narrowerspectrum antibiotics: chest, pyelonephritis, cellulitis, bone
Broad spectrum including Gram
+ ve, Gram –ve, Pseudomonas: neutropenic sepsis, hospital- acquired/
complicated infection
Pivmecillinam Gram –ve (not Pseudomonas or
enterococcus):
Flucloxacillin
Table 9.
- lactamase resistant,
Staphylococcus: skin, bone
4
Cephalosporins
Antibiotic Indications Considerations
Cefalexin
1
st generation)
(
Cefuroxime
2
nd generation)
(
Cefotaxime,
ceftriaxone,
ceftazidime
3
rd generation)
(
Cefepime (
generation)
Tazobactam/
ceftolozane (
generation)
Table 9.
5
Gram + ve infection:
Gram + ve and Gram –ve (Enterobacterales,
H. influenzae): UTI, sinusitis, skin, wound
Broad spectrum (not Pseudomonas,
Enterococcus spp., Bacteroides). Ceftazidime
includes Pseudomonas but activity against
Gram + ve
Gram + ve and Gram –ve (not
4
th
Broad spectrum including
5
th
Pseudomonas: complicated intra- abdominal
and
Carbapenems
Antibiotic Indications Considerations
Imipenem
Meropenem
Ertapenem
Broad spectrum (Gram + ve, Gram –ve,
aerobes, anaerobes, ertapenem does
not cover Pseudomonas): hospitalacquired/ ventilator- associated/ complicated infection, neutropenic sepsis
Table 9.
6
Lipopeptides and polymyxins
Antibiotic Indication Considerations
Lipopeptides
Vancomycin Complicated Gram + ve
Teicoplanin
Polymyxins
Colistin,
polymyxin
including
C. difficile (not absorbed)
Multi- resistant Gram –ve
B
UTI, H. pylori, Lyme disease
UTI
UTI, pneumonia. First- line use in
UTI, VAP
MRSA. Oral for
IV, poor oral absorption.
Give
Dose adjust for
rash,
GFR. SE: allergy,
N&V, C. difficile, cholestasis
Oral bioavailability may vary
IV, amoxicillin PO.
Ampicillin
Dose adjust for
penicillin
Dose adjust for
as per amoxicillin
SE:
GFR. SE: as per
G, rash with EBV
GFR
Tazobactam penetration of
blood– brain barrier. Dose adjust
GFR. SE: as per penicillin G.
for
Myelosuppression in prolonged
use (rare)
Risk of carnitine depletion
SE: as per penicillin G
Dose adjust for
rash,
GFR. SE: allergy,
N&V, cholestasis
UK due to risk of
C. difficile
SE: allergy, rash,
N&V, cholestasis,
haemolysis
Caution: false + ve
MRSA)
urinary glucose and
Coombs test
Ceftriaxone precipitation in urinary/
biliary tracts
Dose adjust for
given with cilastatin to renal
metabolism
SE: N&V, C. difficile, rash, eosino-
philia, plts,
IV to trough serum concentration.
Dose
SE: nephrotoxic (monitor creatinine, care
GFR. Imipenem
LFTs, seizures
with other nephrotoxics), ototoxic, plts
Nephrotoxicity in ~
50
%. Inhaled colistin
for ventilator- associated pneumonia
Table 9.
https://t.me/med1917
7
Inhibitors of protein synthesis
Antibiotic Indications Considerations
Aminoglycosides
Gentamicin Gram –ve infection (activity
Tobramycin
Amikacin
against most Gram + ve and
anaerobes). Tobramycin has
activity against Pseudomonas.
Macrolides
Azithromycin
Clarithromycin
Erythromycin
Amikacin has least resistance
Gram + ve cocci (not enterococci and staphylococci), syphilis, chlamydia.
Tetracyclines and derivatives
Doxycycline Exac erbation COPD, chlamydia,
MRSA
, Lyme disease, mycoplasma,
rickettsiae, brucella, anthrax,
Tigecycline Gram + ve and Gram –ve including
syphilis, malaria prophylaxis
- lactam- resistant st rain s
Other
Clindamycin Gram + ve cocci (not entero-
MRSA, anaerobes
Linezolid Gram + ve cocci,
Chloramphenicol
cocci),
anaerobes, mycobacteria
Gram + ve, Gram –ve, anaerobes,
mycoplasma, chlamydia, con-
Fusidic acid Staphylococci
Table 9.
junctivitis (topical)
8
Inhibitors of nucleic acid synthesis
Antibiotic Indications Considerations
Folate synthesis inhibitors
Trimethoprim Gram –ve: UTI, prostatitis Inhibits creatinine secretion: serum
Co- trimoxazole
(sulfamethoxazole + trimethoprim)
Pneumocystis jirovecii,
infection (eg Shigella, E. coli),
protozoans (eg Cyclospora),
listeria, nocardia
Fluoroquinolones
Ciprofloxacin
Levofloxacin
Moxifloxacin
Broad including Pseudomonas
(not moxifloxacin):
atypical and hospital- acquired chest
infection, infectious diarrhoea
Others
Metronidazole Anaerobic infection: intra-
abdominal, pelvic, oral, soft- tissue.
Bacterial vaginosis. C. difficile
Rifamycins:
• Rifampicin
• Rifabutin
• Rifapentine
Fidaxomicin
Mycobacteria (
bacteria, leprosy), some staphylococci, Legionella, meningococcal
prophylaxis
Narrow Gram + ve: C. difficile
MRSA, VRE,
MRSA
UTI, prostatitis,
TB, non-
TB
SE: nephrotoxic (monitor drug levels
and serum creatinine), vestibular
toxicity, ototoxicity
SE ( with erythromycin): GI,
cholestasis,
P
450
QT. Cytochrome
inhibition ( with
azithromycin): warfarin, rhabdomyolysis with statins, calcineurin
inhibitor levels
CI: pregnancy, <
SE: N&V, C. difficile, fatty liver, idio-
8
pathic intracranial hypertension
Dose adjust in liver dysfunction.
SE: N&V, photosensitivity, LFTS
Risk C. difficile
MAOI: check interactions,
myelosuppression, optic neuropathy
Systemic use limited by
myelosuppression
SE: GI, LFTS
creatinine without
Synergistic action. Good oral ab-
, GI
sorption and tissue/
SE: folate deficiency, K
myelosuppression, haemolysis with
G6PD defici ency
SE: GI irritation, CNS eects
( seizure threshold, headache,
drowsiness, mood change), peripheral neuropathy, tendinopathy
(Achilles),
QT, C. difficile
Good oral absorption. Dose adjust
for liver function.
reaction with alcohol, warfarin
metabolism, peripheral neuropathy
SE: hepatitis (monitor LFTs), GI,
myco-
CNS eects, myelosuppression, red
secretions (urine, saliva, sweat,
sputum, tears)
Poor systemic absorption, cost
yrs (teeth/ bones).
GFR
CSF penetration.
+
, rash,
SE: Disulfiram
383
9 Infectious diseases
9 Infectious diseases
Gram- positive bacteria
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384
Gram- positive cocci
Staphylococci
Staphylococci are skin/ nasal commensals in ~80% of adults. They can also cause
infectious disease. This produces a diagnostic challenge: are the detected organisms causing infection or a contaminating commensal? The answer may lie in the
presence or absence of coagulase, an enzyme which coagulates plasma.
Coagulase- negative staphylococci: eg Staphylococcus epidermidis are less virulent.
Pathogenicity is likely only if there is underlying immune system dysfunction or foreign material (prosthetic valve/ joint,
Staphylococcus aureus is coagulase positive. Presentation:
1
Toxin release causes disease distant from infection. Includes:
• scalded skin syndrome— bullae and desquamation due to epidermolytic toxins (no
mucosal disease, skin loss compared to toxic epidermal necrolysis)
• preformed toxin in food— sudden D&V (p
• toxic shock— fever, confusion, rash, diarrhoea, BP, AKI, multiorgan dysfunction.
Ta mp o n a ss o c ia t e d o r oc c u rs wi t h ( m in o r) l o c al in f ec t i on .
2
Local tissue destruction: impetigo, cellulitis, mastitis, septic arthritis, osteo-
myelitis, abscess, pneumonia,
3
Haematogenous spread: bacteraemia, endocarditis, ‘metastatic’ seeding.
Diagnosis: positive culture from relevant site of infection. Tre atm en t:
p
772
. Drain infected foci, antibiotic (topical/ oral/ IV) based on illness severity and risk
factors. Consider local epidemiology of resistance. If systemic treatment indicated,
use - lactam whenever possible (may need to cover resistant strains until sensitivity
available). Preformed toxin in food: supportive, antibiotics not usually indicated.
Resistant Staphylococcus aureus:
Staph. aureus which produces - lactamase, or an altered enzyme responsible
for cell wall formation, will be resistant to - lactam antibiotics (penicillins, ceph-
alosporins, carbapenems, see
meticillin, ie meticillin- resistant Staph. aureus (
exists and is classified by the amount of vancomycin needed to inhibit bacterial
growth: vancomycin- intermediate Staph. aureus (
Staph. aureus (
VRSA). Resistant staphylococci cause mo rbid ity a nd mo rtal ity c om-
pared to sensitive strains. Risk factors for colonization include: antibiotic exposure,
hospital stay, surgery, nursing home residence. Treatment of infection (not colonization): vancomycin (for
MRSA incl ude co- trimoxazole, doxycycline, linezolid. Prevention: sur veilla nce,
against
barrier precautions, hand- hygiene, decolonization (mupirocin
tree oil), antimicrobial stewardship. See
Streptococci
Classification based on Lancefield group persists in terminology (fig
• Streptococcus pyogenes (- haemolytic group A): colonizes throat, skin, anogenital
tract. Range of infection: tonsillitis, pharyngitis, scarlet fever, impetigo, erysipelas,
cellulitis, pneumonia, peripartum sepsis, necrotizing fasciitis. All can streptococcal
toxic shock = sudden- onset
rare: rheumati c fever (
• Streptococcus agalactiae (- haemolytic group B): neonatal and puerperal infec-
tion, skin, soft tissue. Invasive disease (bacteraemia, endocarditis, osteomyelitis,
septic arthritis, meningitis) usually has risk factors:
ease. Treatment: penicillin, macrolide, cephalosporin, chloramphenicol.
• Streptococcus anginosus: if found in blood culture look for an abscess— mouth,
liver, lung, brain. Treatment: penicillin.
• Streptococcus pneumoniae: pneumonia (pp
caemia. Tre at men t: penicilli n. Vacci nation: childhood, hyposplenism, >
• Viridans streptococci: commonest cause of oral/ dental origin endocarditis (p
• Streptococcus bovis: bacteraemiaendocarditis. Look for colon/ liver disease.
IV line, PD catheter, pacemaker).
424
)
UTI.
Sepsis, see
MRSA, VISA, VRSA
p
381
). Resistance is usually defined by stability to
MRSA), teicoplanin. Oral agents with potential activity
BP, multiorgan failure. Post- infectious complications
p
146
), glomerulonephritis (p
MRSA). Vancomycin resistance also
VISA) and vancomycin- resistant
2
p
380
.
306
168– 71
), otitis media, meningitis, septi-
%, chlorhexidine, tea
). Tre at me nt : pen icill in.
DM, malignancy, chronic dis-
9.5
). Includes:
65
yrs (p
403
144
).
).
Enterococci
OHCS
https://t.me/med1917
Gut commensal. Resistance to cephalosporins and quinolones leads to nosocomial
colonization and infection. Most common is Enterococcus faecalis: if found in blood
culture, assume endocarditis until proven otherwise. Treatment: intrinsic and acquired resistance including vancomycin- resistant enterococci (
VRE). Seek expert help.
Gram- positive bacilli
Listeriosis
Caused by Listeria monocytogenes which lives in soil. Able to multiply at low temperatures. Found in pâté, raw vegetables/ salad, unpasteurized milk/ cheese. Presentation:
most asymptomatic, or mild flu- like illness. In immunosuppressed (including elderly): gastroenteritis, local infection (abscess, osteomyelitis, septic arthritis, endocarditis, pneumonia), meningoencephalitis, life- threatening septicaemia. Listeria in
pregnancy may cause mild disease in mother but transplacental infectionplacentitis,
amnionitis, preterm delivery, neonatal sepsis, intrauterine death. Diagnosis: culture: blood, placenta, amniotic fluid,
cillin plus gentamicin (synergistic action) for systemic disease. Also co- trimoxazole (
disease), macrolides, tetracycline, rifampicin, vancomycin, carbapenem.
to cephalosporins which are often
CSF. PCR. Serology is non- specific. Trea tm en t: ampi-
CNS
Resistant
1
st- line empirical treatment for meningitis so re-
member additional antimicrobial cover if listeria is a possibility.
Clostridia
• Clostridium difficile, see p
• Clostridium perfringens:
• Gastroenteritis, see p
• Gas gangrene due to exotoxin production (alpha toxin most common). Previously
Clostridium welchii. Presentation: sudden, severe pain due to myonecrosis, tissue
crepitus, systemic shock. Most post surgery (
trauma/ open fracture. If spontaneous, look for malignancy. Tre at m en t: early recognition, surgical debridement, protein synthesis inhibitors, eg clindamycin inhibit
toxins > penicillins. Hyperbaric O
• Clostridium botulinum, see p
• Clostridium tetani, see p
Diphtheria
Caused by Corynebacterium diphtheriae toxin. Preventable with vaccine.
Presentation: tonsillar pseudomembrane with fever, painful dysphagia, cer-
vical lymphadenopathy (see
Treatment: antitoxin within
255
, p
407
.
426
.
GI, biliary), or following soft- tissue
unp roven i n tria ls (fig
2
432
.
432
.
p
208
48
). Diagnosis: culture, toxin detection, PCR.
h. Benzylpenicillin/ erythromycin. Airway support.
9.4
, table
9.7
).
Actinomycosis
Due to Actinomyces israelii, a mucous membrane commensal. Presentation: subacute granulomatous/ suppurative infection adjacent to mucous membrane.
Diagnosis: culture. ‘Sulfur’ granules in pus/ tissue are pathognomonic. Treatment:
ampicillin, amoxicillin, or penicillin.
Nocardia
Rare cause of disease. Presentation: tropical skin abscess, lung/ brain abscess, disseminated infection if immunosuppressed. Treatment: usually co- trimoxazole.
Anthrax See p
420
.
385
9 Infectious diseases
Fig 9.
5
Streptococci are grouped by haemolytic pattern (,
, or non- haemolytic), by Lancefield antigen (
cies. Rebecca Lancefield (
lens, typing streptococci with a variety of
antibodies. Her lab became known as the ‘Scotland Yard
of Streptococcal Mysteries’ after she found that the most
grievous crimes of streptococci almost always involve
a secret accomplice. Although she arrested
M outlived her, and still stalks our wards and clinics.
sions,
1895– 1981
© Dr V Fischetti, Rockefeller University, NY.
A– G), or by spe-
) is shown with her hand
M protein- specific
M as
M on many occa-
9 Infectious diseases
Gram- negative bacteria
https://t.me/med1917
386
Gram- negative cocci
Neisseria
Neisseria meningitidis (meningococcus) is an upper respiratory tract commensal in
10
% (~25% adolescents) adhering to non- ciliated epithelial cells in nasopharynx
~
and tonsils. Person- to- person transmission via droplets or upper respiratory tract
secretions. Most strains are harmless but induce immunity. Pathogenic, virulent
strains are mostly encapsulated and have the potential to cause septicaemia and
meningitis. Serogroups
C following introduction of vaccination in UK. in serotype W in UK since
Incubation
2– 7
fects, hyposplenism,
Presentation:
1
Meningitis (~50% cases). Main proliferation of bacteria is in CSF. Insidious onset
with malaise, nausea, headache, vomiting. May be misdiagnosed as gastroenteritis,
nuchal/ back rigidity, photophobia, altered consciousness. Complications in up
20
%: sensorineural hearing loss, impaired vestibular function, epilepsy, dif-
to
fuse brain injury.
2
Meningococcaemia. Symptoms/ signs depends on amount of circulating bac-
teria. Mild disease presents with fever, macular rash (
shock. High- grade meningococcaemia (~
shock within
failure, coagulopathy with skin haemorrhage (
ities/ adrenals,
tion, skin necrosis, pericarditis, arthritis, ocular infection, pneumonia (especially
serotypes
A, B, C, W, & Y account for nearly all invasive forms. Group
d. Peak ages: <2yrs, ~18yrs. Risk factors: complement system de-
HIV.
URTI, or childhood viral illness. Later meningism: headache, vomiting,
fig
30
6– 12
h due to rapidly escalating endotoxin levels: circulatory
% cases) causes pyrexia and septic
fig
AKI, ARDS. Meningism may be absent. Complications: amputa-
Y and W), permanent adrenal insuciency.
9.6
9.7
), thrombosis of extrem-
2009
) but no signs of
.
Fig 9.
6
Macular lesions on legs.
Reproduced from Warrell et al., Oxford Textbook
of Medicine,
2010
, with permission from Oxford
Diagnosis: Start treatment immediately if meningitis/ meningococcal sepsis is
a possible diagnosis
extracellular diplococci on microscopy of
skin lesion. Tre at me nt : urgent antibiotic treatment: benzylpenicillin, ceftriaxone
pp
806– 7
). Also cefotaxime, chloramphenicol, meropenem. Prevention: routine infant
(
vaccination against capsular groups
unknown. Quadrivalent
able groups (
or rifampicin
p
403
). Prophylaxis of contacts: ciprofloxacin/ ceftriaxone (single dose),
600
mg BD for 48h; ACWY vaccination.
Neisseria gonorrhoeae: see
Moraxella catarrhalis
Colonizes upper respiratory tract in children ( in adults). Resembles Neisseria commensal so may be overlooked. Presentation: pneumonia, exacerbation of
20
% of acute otitis media, sinusitis. Bacteraemia is rare. Diagnosis: culture of sputum,
ear eusion, sinusitis. Bacteraemia is rare. ‘Hockey puck sign’: colonies can be pushed
along agar surface without disruption. Tre at me nt : macrolide, cephalosporin.
Fig 9.
7
Massive skin haemorrhage with ful-
minant meningococcal septicaemia.
University Press.
Reproduced from Burge et al., Oxford Handbook of
Medical Dermatology,
2016
, with permission from
Oxford University Press.
. Do not wait for confirmation: delay can be deadly. Intra- and
CSF/ blood/ skin lesion. PCR of CSF/ blood/
ACWY vaccine at age
B and C in UK: duration of protection in group B
14
. Additional B, C, ACWY doses if vulner-
p
409
.
COPD, up to
Gram- negative bacilli
https://t.me/med1917
Enterobacterales
Enterobacterales family is large: >50 genera, >
3
species make up 80– 95% of isolates:
setting,
1
Escherichia coli: part of normal colonic flora. Pathogenic forms can cause:
Enterotoxigenic: a major cause of traveller’s diarrhoea (
Enterohaemorrhagic: diarrhoea, haemorrhagic colitis, eg
Enteropathogenic: infant diarrhoea in areas of poor sanitation.
Enteroinvasive: dysentery- like syndrome.
Enteroadherent: traveller’s diarrhoea, chronic diarrhoea in children/
Extra- intestinal disease: usually commensal flora, pathogenic outside of the gut:
UTI ( pp
292– 3
trimethoprim, ampicillin, cephalosporin, ciprofloxacin, aminoglycoside.
2
Klebsiella pneumoniae: colonizes skin, nasopharynx, GI tract, hospitalized
patients. Associated with antibiotic exposure, in- dwelling catheters, im-
); nosocomia: pneumonia, meningitis, sepsis. Treat by susceptibility:
munosuppression. Causes pneumonia (necrotizing disease and sepsis if immunosuppressed). Also
susceptibility: aminoglycoside, cephalosporin, carbapenem, quinolone.
3
Proteus mirabilis: gut commensal. Causes UTI (pp
to urease production: breaks down urea to produce ammonia, struvite stones
then form in the presence of magnesium, calcium, and phosphate (
Other: Salmonella, Shigella, Yersinia: see enteric fever (
pp
424– 29
), plague (p
(
421
Resistant Enterobacterales:
Widespread antibiotic use has led to the development of highly virulent, multiple
resistant E. coli and Klebsiella species including:
• Extended- spectrum - lactamase (ESBL) resistance to penicillins, cephalosporins.
Tre at by s us ce pt ib il it y: ca rb ap en em s, qu in ol on es , am in og lyc os id e.
• Carbapenemase- producing Enterobacterales (CPE) resistant to carbapenems.
Prevention Antimicrobi al stewards hip (pp
Pseudomonas aeruginosa
Environmental pathogen. Spread by contact/ ingestion. Presentation: nosocomial infection. Infection of compromised tissue, eg wound, pneumonia with lung disease or
ventilation,
ciprofloxacin, ceftazidime, piperacillin-tazobactam, aminoglycoside, colistin (not
UTI with catheterization. Septicaemia if immunosuppressed. Trea tm en t:
ertapenem). Combination may be needed. Impermeability of membrane and biofilm
colonization resistance. Multidrug- resistance.
Haemophilus influenzae
Divided into encapsulated, typeable forms (a– f); and unencapsulated, non- typeable
forms. Upper respiratory tract carriage, transmitted by droplets. H. influenzae b
(Hib) causes meningitis, epiglottitis, otitis media, pneumonia, cellulitis, septic arthritis, and bacteraemia. Fatal in ~
ectomy/ hyposplenism (
p
Treatment: amoxicillin, macrolide, cephalosporin, chloramphenicol, rifampicin.
Whooping cough
Bordetella pertussis. Presentation: catarrhal phase 1– 2wks, then paroxysmal
coughing. ‘Whoop’ is a breath through partially closed vocal cords, seen mainly in
children. Cough is prolonged (‘
Diagnosis:
PCR nasal/ throat swab. Culture sensitivity
infectivity, but may not alter disease course. Routine childhood vaccination.
Vacc inat ion i n pr egnan cy placental antibody transfer to protect neonate (
Other
Burkholderia pseudomallei causing melioidosis in tropical water/ soil. Causes pneumonia, pleural eusions, pulmonary abscess. Systemic abscess if haematogenous
spread. Treatment: ceftazidime/ meropenem. Co- trimoxazole eradication therapy.
Also Brucellosis (
p
420
), cholera (p
170
named species. In the clinical
pp
424– 5
).
O
157:H7
(p
427
).
HIV.
UTI, nasopharyngeal inflammation. Treat according to
292– 3
). Stone formation due
pp
630– 1
p
411
), gastroenteritis
).
ESBL, CPE
379– 80
), robust infection control (p
Seek expert help.
5
%. Routine immunization in childhood and splen-
403
). Non- typeable forms cause pneumonia and sinusitis.
100
- day cough’). Infants have complications/ mortality.
426
).
10– 60
%. Tr ea tm en t: macrolides
p
403
407
).
387
9 Infectious diseases
).
).
9 Infectious diseases
Tuberculosis (TB): presentation
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388
Epidemiology
• 10 million new cases/ yr of which 30% are unreported/ undiagnosed (fig
• 3.3% of new cases, and 18% of previously treated cases are drug resistant (p
• Co- infection with HIV in 9.5% of new cases. TB risk 19- fold higher if HIV positive.
• Leading cause of death worldwide, 1.5 million deaths/ yr.
• Eective diagnosis and treatment saved 58 million lives between
• UK ~
8000
/ yr, ~12 per
with pulmonary disease wait >
Incidence per
100 000
0–9.9
10
–
49
50
–
99
100
–
299
300
–
499
500
Fig 9.
8
Estimated TB incidence rate worldwide.
Reproduced with permission from World Health Organization, Global tuberculosis report
© World Health Organization
Pathophysiology
Caused by infection with Mycobacterium tuberculosis.
Active infection occurs when containment by the immune system (T cells/ macro-
phages) is inadequate. It can arise from primary infection, or re- activation of
previously latent disease. Transmission of
containing bacterium. This means only pulmonary disease is communicable.
Latent TB is infection without disease due to persistent immune system contain-
ment (ie granuloma formation prevents bacteria growth and spread). Positive skin/
blood testing (
non- infectious (normal sputum/
p
390
) shows evidence of infection but the patient is asymptomatic and
population) are estimated to have latent
factors for reactivation: new infection (<
suppression (including corticosteroids), silicosis, illicit drug use, malnutrition, highrisk settings (homeless shelter, prison), low socio- economic status, haemodialysis.
Presentation
TB, or not TB? That is the question. Maintain a high index of suspicion. TB can aect
any organ in the body (
Table 9.
9
UK TB case reports by site of disease.
Site of disease
Pulmonary
Extrathoracic lymph nodes
Intrathoracic lymph nodes
Pleural
Gastrointestinal
Spine
Other bone
Miliary
Meningitis
Genitourinary
Source data from: Tuberculosis in England
100 000. 72
table
% born outside UK, 70% in deprived areas, 29%
2000
4
months from symptoms to treatment.
2022
. http:// www.who.int/ tb/ publi cati ons/ global _ rep ort/ en/
TB is via inhalation of aerosol droplets
CXR). ~
2
billion persons worldwide (~⅓ of world’s
TB. Lifetime reactivation risk is
2
yrs), HIV, organ transplantation, immuno-
9.9
).
%
of cases in
57
20
2
9
5
3
1
3
3
2
2019
Report, Public Health England. www.gov.uk/ phe
UK
9.8
and
5– 10
).
391
2018
%. Risk
2022
).
.
.
Clinical features of
https://t.me/med1917
TB
• Systemic features Low- grade fever, anorexia, weight loss, malaise, night sweats,
p
560
clubbing (bronchiectasis), erythema nodosum (
• Pulmonary TB Cough (in ~50%, >2– 3 weeks, dry then productive), pleurisy, haem-
optysis (uncommon, seen with bronchiectasis not always active disease), pleural
eusion. An aspergilloma/ mycetoma (
varies and may be silen t or atypical, especially with immunosuppression, eg
post- transplantation.
• Tu be rc ul ou s l ym ph ad en it i s (Usually) painless enlargement of cervical or
supraclavicular lymph nodes. Axillary and inguinal node involvement less common.
Coexisting systemic symptoms in
acutely inflamed (‘cold abscess’). Skin can adhere to the underlying mass with risk
of rupture and sinus formation. Can occur with or without pulmonary disease.
Investigate with fine- needle aspiration,
• Gastrointestinal TB Most disease is ileocaecal. Causes colicky abdominal pain and
p
174
40– 50
AFB sta ining , and c ulture (p
).
) may form in the cavities. Presentation
HIV,
%. Node is typically firm to touch and not
390
).
vomiting. Bowel obstruction can occur due to bowel wall thickening, stricture formation, or inflammatory adhesions. Biopsy is required for diagnosis. Caseation necrosis
and an absence of transmural cracks/ fissures distinguish from Crohn’s disease.
• Spinal TB Local pain and bony tenderness for weeks– months. Slow, insidious pro-
gression. May not present until deformity or neurological symptoms. Look for bony
destruction, vertebral collapse, and soft tissue abscess (see Pott’s vertebra,
• Miliary TB Haematogenous dissemin-
ation leads to the formation of discrete
2
mm) of granulomatous tissue
foci (~
throughout the lung (‘millet’ seed appearance).
throughout the body with meningeal
involvement in ~
negative for
togenous. Have a low threshold for
Untreated mortality is assumed to be
close to
while test results are pending.
•
CNS TB
leading to foci of infection in brain and
CXR: fig
9.9
. Dissemination
25
%. Sputum may be
AFB as spread is haema-
100
%. Do not delay treatment
LP.
Haematogenous spread
p
694
).
spinal cord. Foci can enlarge to form
tuberculomas. Foci rupture leads to
meningitis. Risk with immune sup-
HIV, aged <
pression,
meningism, confusion, seizures, focal
neurological deficit, and systemic symptoms. Needs
(leucocytosis, raised protein,
ture). Look for
alus, basal exudates. Tuberculomas are ring- enhancing. All rapid diagnostic tests
p
390
) have sensitivity, so treat on suspicion.
(
• Genitourinary TB Symptoms may be chronic, intermittent, or silent. Include dys-
3
yrs. Headache,
TB elsewhere (CXR, etc,), test for HIV. CT/ MRI may show hydroceph-
uria, frequency, loin pain, haematuria, sterile pyuria (
fibrosis, strictures, infertility, and genital ulceration.
• Cardiac TB Usu ally in volves the per icardi um: perica rditis , pericard ial eusion, and/
or constrictive pericarditis (
Fig 9.
9
Miliary TB (nodular opacities).
© Dr Vijay Sadasivam, Radiologist, SKS Hosp,
CSF: plasma glucose <
p
132
). Check chest imaging for other TB pathology,
Salem, Tamil Nadu, India.
LP and examination of CSF
50
%, AFB stain, PCR, and cul-
p
292
). Granuloma may cause
eg pulmonary disease, mediastinal lymph nodes. Pericardiectomy may be indicated
for persistent constriction despite antituberculous treatment. Myocardial involvement (arrhythmias, heart failure, ventricular aneurysm, or outflow obstruction)
is rare.
• Skin Lupus vu lgaris = persistent, progressive, cutaneous TB: red- brown, ‘apple- jelly’
nodules. Scrofuloderma: skin lesion extended from underlying infection, eg lymph
node, bone; causes ulceration and scarring.
389
9 Infectious diseases
9 Infectious diseases
Tuberculosis (TB): diagnosis and treatment
CXR
TB
https://t.me/med1917
390
Diagnostic tests for
Latent
TB
Oer testing3 to close contacts of those with pulmonary or laryngeal TB, those
with immune dysfunction, healthcare workers, and high- risk populations, eg
prison, homeless, vulnerable migrants.
• Tub er cul in sk in tes ti ng (
tein derivative (
tivity depending on vaccination history and immune status (>
15
mm if no risk factors).
>
• Interferon- gamma release assay (
release of interferon- gamma from
pared to
PPD) tuberculin. Size of skin induration is used to determine posi-
TST if history of BCG vacc inati on.
Neither test can diagnose or exclude active disease (falsely negative in 20– 25%
of active disease): clinical evaluation is required.
Immune- suppressed states reduce the sensitivity of both tests.
Active pulmonary
•
: fibronodular/ linear opacities in upper lobe (typical), middle or lower lobes
TB
(atypical), cavitation, calcification, miliary disease (see
lymphadenopathy.
• Sputum smear: sputum can be spontaneously produced or induced (with nebulized
saline and precautions to prevent transmission). Three specimens are needed including an early- morning sample. It is stained for the presence of acid- fast bacilli
AFB). All mycobacteria are ‘acid- fast’ including M. tuberculosis. If AFB are seen,
(
treatment should be commenced and the patient isolated (in hospital only if clinical
indication, or public health reason for admission; or at home).
• Sputum culture: more sensitive than smear testing. Culture takes 1– 3 weeks (liquid
• Nucleic acid amplification test (
Extrapulmonary
4– 8
media) or
by
p
391
(
wee ks (so lid media ). Can a ssess drug s ensit ivity.
DNA or RNA ampli ficatio n. Rapid dia gnosis (<
).
TB
• Investigate for coexisting pulmonary disease alongside site- specific imaging.
• Obtain material from aspiration or biopsy (lymph node, pleura, bone, synovium,
GI/ GU tract) to enable AFB staining, histological examination (caseating granu-
loma) and/ or culture.
• NAAT can b e carr ied ou t on any steri le bod y fluid , eg CSF, pericardial fluid.
Oer HIV test for all.
Treatment
Antibiotics used in the treatment
Table 9.
10
Antibiotics used in the treatment of sensitive
Antibiotic
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
Standard course for
active disease
2
months intensive
4
months continuation
2
months intensive
4
months continuation
2
months intensive Idiosyncratic hepatotoxicity, dose if e
2
months intensive
TB
TST
): = Mantoux test. Intradermal injection of purified pro-
5
mm if risk factors,
IGRA
): diag nose e xposu re to TB by measuring the
T cells reacting to TB antigen. Specificity com-
fig
9.9
, p
389
NAAT
): dir ect d etect ion o f M. tuberculosis in sputum
8
h). Can also detect drug resistance
3 of TB are detailed in table
Notes
Enzyme inducer: care with warfarin,
calcineurin inhibitors, oestrogens, phenytoin;
body secretions coloured orange- red (includes
contact lens staining); altered liver function
Inhibits formation of active pyridoxine (vit B
which causes a peripheral neuropathy (risk
DM, CKD, HIV, malnutrition) give with
with
prophylactic pyridoxine; hepatitis
Colour blindness, visual acuity, optic neuritis. Check visual acuity at start of treatment,
monitor for symptoms. Monthly visual check if
treatment >
2
9.10
.
month s. Monito r levels if eGFR<
), eusion,
GFR<
30
)
6
30
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