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8 Haematology
Other risk factors for thrombosis
OHCS
OHCS
https://t.me/med1917
Arterial Venous
• Smoking. • Surgery.
• Hypertension. • Trauma.
• Hyperlipidaemia. • Immobility.
• Diabetes mellitus. • Pregnancy, oestrogen- containing oral contraceptive pill,
*
PNH, HIT,
and antiphospholipid antibody syndrome can cause both arterial and
• Age.
• Obesity.
• Varicose veins.
• Other conditions: heart failure, malignancy, inflammatory
bowel disease, nephrotic syndrome, sickle cell anaemia,
paroxysmal nocturnal haemoglobinuria (
PNH
)* (p
334
HRT.
).
venous thrombi.
If there are recurrent clots despite adequate anticoagulation, consider occult
HIT,
malignancy,
For thrombophilia in pregnancy, see
and thromboprophylaxis, see
or antiphospholipid antibody syndrome.
p36; for anticoagulant use in pregnancy
p36.
371
Antiphospholipid syndrome (
APLS
is an autoimmune multisystem disorder characterized by arterial, venous, or
APLS
)
small vessel thromboembolic events and/ or pregnancy morbidity in the presence
of persistent antiphospholipid antibodies. It can occur as a primary condition or
in the setting of an underlying systemic autoimmune disease, particularly
Other manifestations include thrombocytopenia, livedo reticularis, Libman– Sacks
endocarditis, or renal disease.
The diagnosis requires at least one of two clinical criteria and at least one of
three laboratory criteria to be met:
Clinical criteria
• One or more otherwise unexplained venous or arterial thrombotic events.
• Pregnancy morbidity including fetal death after 10 weeks’ gestation, premature
birth due to severe pre- eclampsia or placental insuciency, or multiple embryonic
10
wee ks’ ge statio n).
losses (<
Laboratory criteria
• Lupus anticoagulant assay.
• IgG or IgM ant icardi olipi n anti body t est.
• IgG or IgM ant i- 2 gly coprot ein 1 ant ibody test.
One or more of these antibodies must be present on two or more occasions at
12
weeks apart.
least
Tre at me nt
None for asymptomatic patients but pregnant patients may need low- dose aspirin
LMWH.
Anticoagulation with warfarin for acute thromboembolism. Catastrophic
or
APLS
, a rare, life- threatening form of
cular thrombosis with multi- organ failure, is treated with anticoagulation, glucocorticoids, and, in severe cases, plasma exchange and/ or
APLS
characterized by disseminated intravas-
IV
im muno glob ulin .
SLE.
8 Haematology
Immunosuppressive drugs
BNF
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372
As well as being used in leukaemias and cancers, immunosuppression is required in
organ and marrow transplants, and plays a role in the treatment of many diseases:
rheumatoid arthritis, psoriasis, autoimmune hepatitis, asthma,
IBD
, to name a few.
SLE
Prednisolone Steroids can be life- saving, but bear in mind:
• Long- term steroids (>3 weeks, or repeated courses) must not be stopped sud-
Risk of Addisonian crisis due to adrenal insuciency, see p
denly.
gradual taper over weeks (with the advice of an endocrinologist if needed).
• Certain conditions may be made worse by steroids, eg
chickenpox, osteoporosis, diabetes: here careful monitoring is needed.
• Growth retardation may occur in young patients, and the elderly frequently get
SE
from treatment.
more
• Interactions: ecacy is reduced by anti- epileptics (see later in topic) and
rifampicin.
• Caution in pregnancy (may cause fetal growth retardation). See
breastfeeding.
Side eects Multiple and serious (table
dose possible for the shortest period of time. Prescribe calcium and vitamin
plements to reduce risk of osteoporosis (
8.11
): minimize these by using the lowest
p
674
) or consider bisphosphonates. Before
starting long- term treatment, explain clearly the potential
sure they are aware of the following:
• Do not stop steroids suddenly (p
• Consult a doctor if unwell; steroid dose (eg if requiring antibiotics or surgery).
• Carry a steroid card stating dose taken, and the indication.
• Avoid over- the- counter drugs, eg
• Exercise and smoking cessation help to prevent osteoporosis.
819
).
NSAID
S: aspirin and ibuprofen (risk of
TB,
SE
to patients and en-
Azathioprine SE Diarrhoea, abdominal pain, marrow suppression (anaemia,
lympho penia), pancreatitis, transaminitis.
azathioprine (which is metabolized to mercaptopurine) are metabolized by xanthine
XO
oxidase (
inhibitors (eg allopurinol).
typically weekly
). So toxicity results if full- dose azathioprine co- administered with XO
Monitoring Local guidelines should be in place to guide;
FBC, U&E,
creatin e
, LFT
Interactions Mercaptopurine and
dur ing ini tiation then 1– 3- monthly once stable.
Ciclosporin, tacrolimus Calcineurin inhibitors with important roles in reducing re-
SE
jection in organ and marrow transplant. The main
check blood levels.
• Other SE: gum hyperplasia (ciclosporin), tremor, BP (stop if ), oedema, paraesthe-
siae, confusion, seizures, hepatotoxicity, lymphoma, skin cancer— skin protection
• Monitor
U&E
dose >
specialist advice if creatinine increasing. Also monitor
• Interactions are legion: potentiated by: ketoconazole, diltiazem, verapamil, the Pill,
erythromycin, grapefruit juice. Ecacy is reduced by: barbiturates, carbamazepine, phenytoin, rifampicin. Concurrent
LFT
and creatinine every 2 weeks for the first 3 months, then monthly if
2.5
mg/ kg/ d (every 2 months if less than this). Check blood level and seek
NSAID
. Check with pharmacists if unsure regarding potential interaction.
is dose- related nephrotoxicity:
LFT
.
S augment hepatotoxicity— monitor
Methotrexate An antimetabolite. Inhibits dihydrofolate reductase, which is in-
p
543
volved in the synthesis of purines and pyrimidines. See
.
Cyclophosphamide An alkylating agent. SE: marrow suppression (monitor
nausea, infertility, teratogenic, haemorrhagic cystitis due to an irritative urinary
metabolite. There is a slight risk of later developing bladder cancer or leukaemia.
Rituximab Monoclonal antibody that targets the
Pre- treatment Screen for recent or recurrent infections. Check
levels. Vaccinate for pneumococcus and influenza prior to treatment.
B
- cell depletion defined as
CD19
levels <5 cells/ microlitre. Side eects Infusion reac-
tions, serum sickness, infections (eg reactivation of
CD20
antigen and depletes B cells.
CXR, HBV/ HCV/ HIV, I
TB, HBV
).
, vasculitis, and
819
. Plan a
hypertension,
for use in
D
sup-
DU
).
NB
FBC
Monitoring
.
),
g
8 Haematology
Table 8.
https://t.me/med1917
11
Side eects of steroid use
System Adverse reactions
Gastrointestinal Pancreatitis
Musculoskeletal Myopathy
Endocrine Adrenal suppression
CNS
Eye Cataracts; glaucoma
Immune Increased susceptibility to and severity of infections, eg chickenpox
Steroids can also cause fever and
Candidiasis
Oesophageal ulceration
Peptic ulceration
Osteoporosis
Fractures
Growth suppression
Hypertension, diabetes, Cushing’s syndrome
Aggravated epilepsy
Depression; psychosis
Papilloedema
WCC
; steroids only rarely cause leucopenia.
From Frankenstein to ciclosporin: unleasing immune control
Since the publication of Mary Shelley’s Frankenstein in
1818
, the concept of utilizing another person’s organs to extend or enhance the life of another has captivated both the medical community and the general public. However, it wasn’t until
19
th century that this notion began to materialize in the real world. A key
the late
milestone was the discovery of the immunosuppressant eects of ciclosporin
1970
in the
ation of immunosuppressive drugs called
s—the first of a new gener-
calcineurin inhibitors that could prevent
organ rejection without the harmful toxicity of available products. Ciclosporin
was first discovered in Norway in
Sandoz biologist Dr Hans Peter Frey from
1969
by
a soil sample collected in a plastic bag by
a Sandoz employee on a trip (the company encouraged employees to collect
such samples on business trips and holidays to search for new antibiotic drugs
from fungal metabolites). Although
initially investigated as an anti-fungal
antibiotic, fellow Sandoz researcher Dr
Jean Borel discovered the compound’s
promise in suppressing
immune system. A purified form was
synthesized in
including trials on humans, revealed its
1973
T
-cells in the
, and further research,
potential for preventing organ rejection.
While transplantation remains a significant medical procedure, and chronic rejection can be burdensome, ciclosporin
played a crucial role in advancing medical science and turning a fantastical idea
Fig 8.
80
Victor Frankenstein observ ing
the first stirrings of his creature.
Source: Engraving by W. Chevalier after Th.
von Holst,
1831
. Public Domain Mark. Source:
Wellcome Collection.
into reality.
373
9
https://t.me/med1917
Infectious diseases
Contents
What is life?
Infectious disease: an overview
Bacterial infection
Bacterial infection: an overview
Antibiotics
Antibiotics: summary tables
Gram- positive bacteria
Gram- negative bacteria
Tuberculosis (TB): presentation
Tuberculosis: diagnosis and
treatment
Viral infection
Influenza
Human immunodeficiency virus (
diagnosis
Complications of
HIV
Herpes viruses
Other viruses
Other
Immunization
Fungi
Healthcare- associated (nosocomial)
infection
Sexually transmitted infection (
Imported and unusual infection
Fever in the returning traveller
Enteric fever
Malaria: diagnosis
Malaria: treatment
Mosquito- borne disease
Vector- borne disease
Zoonoses
Viral haemorrhagic fever (
Gastroenteritis: an overview
Gastroenteritis: specific infections
Gastrointestinal parasites
Schistosomiasis and liver disease
Neurological disease
Eye disease
Skin disease
Pyrexia of unknown origin (
Eliciting the weird and the wonderful
375
380
390
392
394
HIV
402
403
infection
400
antiretroviral therapy (
404
406
411
412
414
434
436
418
432
420
384
386
416
ART
VHF
428
PUO
382
)
)
424
396
STI
)
376
378
388
HIV
):
398
Fig 9.
1
Alexandre Yersin travelled a literal and
metaphorical half world away from the Pasteur
Institute in Paris to work in French IndoChina in
1890
)
410
422
426
430
438
. His medical fame was etched in a bamboo
408
hut during the
Kong. He bribed morgue guards to acquire specimens from the dead and isolated the causative organism, later named Yersinia pestis in his
honour. Yersin remained in IndoChina, directing
Hanoi’s first medical school, and establishing a
medical laboratory in Nha Trang. He also delved
into botany, introducing to the region the rubber
tree, and the cinchona tree used to produce
quinine. Of medicine, he said, ‘I am very happy to
treat those who come to me asking for advice,
but I wouldn’t like to make medicine my profession ... I consider medicine a calling, like priesthood.’ He was the Ông Nam (fifth uncle) of many
in Vietnam. Buried in his adopted home of Nha
Trang, he remained to the last an eccentric, eclectic, and humble polymath. And so we too aspire to balance humanitarianism with forensic
attention to detail in our approach to infectious
disease.
439
Source: Wellcome Collection, Public Domain Mark.
1894
outbreak of plague in Hong
La peste bubonique à Hong-Kong / A.E.J. Yersin.
Wellcome Collection.
We thank James Whitehorn, our Specialist Reader and Adam Komorowski, our Junior Reader for this
chapter.
What is life?
https://t.me/med1917
By convention, life is anything which is organic and converts nutrients into progeny. Failure to meet this definition means non- living, dead, or dying. Life is a
thing of dynamism, fragility, beauty, danger, and evanescence; gushing forth
from a single source. But here the certainties end: what does it really take to be
alive? Are viruses and prions living? How many branches are there on our tree?
The harder we look, the more complexities we find. The Hillis plot is a circular
phylogenetic tree, and a representation of humanity’s place in nature. We are duly
humbled by this challenge to our imagined self- importance, reminding us that we
do not in reality occupy a privileged position in the hierarchy of the living, just a
unique subunit
Fig 9.
million species that are formally named. The image on the right is a close up of the ‘animal’ segment of the diagram (upper left quadrant) showing ‘You are here’.
RNA sequence (fig
2
Tree of life based on subunit
Copyright David M. Hillis, Derrick Zwickl, and Robin Gutell, University of Texas.
9.2
).
RNA
sequences sampled from ~
http:// www.zo.ute xas.edu/ facu lty/ antise nse/ downl oadfi les ToL.html
3000
species out of the 1.7
Because micro- organisms kill our friends, we think of them as bad, ‘I have no phil-
osophy, nor piety, no art of reflection, no theory of compensation to meet things so
hideous, so cruel, and so mad, they are just unspeakably horrible and irremediable
to me and I stare at them with angry and almost blighted eyes.’ (Henry James,
1915
, describing the death of Rupert Brooke from septicaemia.)
But this is a mistake. Kill o micro- organisms and the whole show fizzles out.
Micro- organisms gave us the
DNA and organelles needed for reading and
digesting this page. Even killing a single pathogen might be a mistake: Sod’s
Law will probably ensure that something worse will come to inhabit the vacated ecospace. Prod one part of the system and events ripple out in an unending
stream of unintended consequences, played out under the stars, which themselves are evolving, and which donate and receive our primordial elements.
Can we win against infectious diseases? No. But winning or losing is the wrong
image: infectious diseases have made us who we are. All we can do is live with
them. To help us do this in ways that are not too destructive we need robust
public health surveillance, sound vector- control policies, political will, quarantine
laws, openness, and cooperation. Most importantly, do not underestimate the importance of maintaining our infectious cohabitants in their apparent subordinate
position. The speed and capacity for learning by ribonucleic malware and singlecelled organisms is amazing. So do not inadvertently teach them. Preserve your
precious warfare tactics. Expose them to antibiotic therapies only in a stand- o
situation from which they cannot return to fight again.
375
9 Infectious diseases
9 Infectious diseases
Infectious disease: an overview
https://t.me/med1917
376
It is not possible for any ID chapter to be constructed so that it has the right balance
throughout the world. Many of our readers come from communities where malaria is
the primary dierential, and
GU, and ENT infections which predominate in the UK; and AIDS is considered only where
there is failure of either diagnosis or treatment of
and free at the point of care. Many of the diseases in this chapter cause multisystem
pathology. For these infections, it may be helpful to classify by pathogen (
However, infectious agents do not walk in the door and introduce themselves. Detective
work may be necessary based on geography; or exposure: to vectors, animals, and contaminated water/ food. And so other pages in this chapter have that as their (helpful)
premise. When infection is organ specific, you may need to look elsewhere (
Table 9.
1
Infectious disease by pathogen (illustrative, not exhaustive)
Bacteria Viruses
Gram positive
Staphylococci:
• Staph. aureus (coagulase + ve)
• Staph. epidermidis (coagulase –ve)
Streptococci:
• - haemolytic, eg Strep. pneumoniae
• - haemolytic, eg Strep. pyogenes
Enterococci
Clostridium species:
• C. botulinum (botulism)
• C. perfringens (gas gangrene)
• C. tetani (tetanus)
• C. difficile (diarrhoea)
Gram negative
Neisseria:
• N. meningitidis (meningitis)
• N. gonorrhoeae (gonorrhoea)
Helicobacter pylori
Escherichia coli
Shigella species
Salmonella species Candida
Campylobacter jejuni Pneumocystis jirovecii
Klebsiella pneumoniae Cryptococcus
Pseudomonas aeruginosa
Haemophilus influenzae
Bordetella pertussis (whooping cough) Entamoeba histolytica
Vibrio cholerae (cholera) Giardia lamblia
Yersinia pestis (plague) Cryptosporidium species
Mycobacteria
M. tuberculosis Plasmodium species (malaria)
M. leprae Leishmania species (leishmaniasis)
Intracellular bacteria
Chlamydia
Rickettsia (rickettsial disease)
Coxiella burnetii
Spirochaetes Trematodes
Borrelia burgdorferi (Lyme disease) Schistosoma (schistosomiasis), flukes
Treponema (syphilis, yaws)
Leptospira (Weil’s disease)
AIDS- related deaths are common. In contrast, it is chest,
HIV, which are universally available
table
9.1
table
9.2
).
RNA
viruses
Picornavirus (‘tiny
• Rhinovirus
RNA’):
• Poliovirus
Calicivirus (‘cup’), eg Norwalk
Flavivirus (‘yellow’):
• Dengue • Zika • Yellow fever
Coronavirus (‘crown’), eg
Rhabdovirus (‘rod’), eg rabies
Filovirus (‘thread’), eg Ebola/ Marburg
Paramyxovirus (‘near mucus’), eg mumps
DNA
viruses
Hepadnavirus (‘liver DNA’): eg hepatitis
Parvovirus (‘small’): eg parvovirus
Herpesvirus (‘spreading’)
SARS- CoV-
2
(COVID- 19)
B
B19
• HSV
• EBV
• VZV
• CMV
Fungi
Parasites
Protozoa
Toxoplasma gondii
Trypanosoma species (trypanosomiasis)
Nematodes
Soil- transmitted helminths
Filarial disease
Cestodes
Hydatid disease, tapeworm
).
Table 9.
GI
OHCS
OHCS
OHCS
https://t.me/med1917
2
Infectious disease by organ system
System Infection Page
Respiratory
GU
and
gynaecology
Cardiovascular
Nervous
system
Skin and soft
tissue
Bone and joint
ENT
Eye
Pneumonia
SARS- CoV-
Empyema— infected pleural eusion
Fungal infections of the lung
Peptic ulcer disease
Gastroenteritis
Colitis, proctitis, diverticulitis, appendicitis
Viral hepatitis
Tropical liver disease
Cholecystitis, cholangitis, gallbladder empyema
Peritonitis
Lower urinary tract infection, cys titis, pyelone phritis
Cervicitis, vulvovaginitis
Genital ulceration
Genital warts
Pelvic inflammatory disease, endometritis
Infective endocarditis
Myocarditis
Pericarditis
Meningitis, encephalitis, subdural empyema
Infective neuropathy
Skin ulcers, gangrene
Tropical skin disease
Surgical wound infection
Osteomyelitis
Septic arthritis
Pharyngitis, laryngitis, otitis media
Tropical eye disease
The management of infectious disease includes prevention whenever possible.
Tracing the source of disease and contacts are essential in the management of outbreaks. Notification to your local health protection team (see
nce/ not ifia ble- disea ses- and- causat ive- organi sms- how- to- rep ort
for the following conditions (only clinical suspicion is required, accuracy of diagnosis is secondary):
• Acute encephalitis
• Acute infectious hepatitis
• Acute meningitis
• Acute poliomyelitis
• Anthrax
• Botulism
• Brucellosis
• Cholera
• Diphtheria
• Enteric fever
• Food poisoning
Infectious disease resources
fig
9.2
, p
The Hillis plot (
We therefore direct you to the following excellent resources:
• Public Health England: https:// www.gov.uk/ topic/ hea lth- pro tect ion/ inf ecti ous- disea ses
• World Health Organization (
375
• US Centers for Disease Control and Prevention: http:// www.cdc.gov
• European Society of Clinical Microbiology and Infectious Diseases: www.escid.org
pp
2
(COVID- 19)
168– 171
pp
172–3
p
175
p
174
p
248
pp
424– 29
p
255
, p
600
, p
274
430– 1
626
598
292– 3
408– 9
408– 9
402
144–5
130– 1
132
806– 9
500– 1
652– 3
436– 7
576
540
434– 5
620
p
134
, p
580
p
502
p
394
p
pp
p
p
pp
pp
pp
p
pp
pp
p
pp
pp
pp
pp
p
p
pp
https:// www.gov.uk/ guida
) is a statutory duty in the UK
• HUS
• Infectious dysentery
• Invasive group A strep
• Legionnaire’s disease
• Leprosy
• Malaria
• Measles
• Meningococcal sepsis
• Mumps
• Plague
• Rabies
• Rubella
• SARS
• SARS- CoV- 2 (COVID- 19)
• Scarlet fever
• Smallpox
• Tetanus
• Tuberculosis
• Typhus
• Viral haemorrhagic fever
• Whooping cough
• Yellow fever.
) tells us that ID chapters will always fail to be exhaustive.
WHO
): http:// www.who.int/ top ics/ en/
377
9 Infectious diseases
9 Infectious diseases
Bacterial infection: an overview
(a)
(b)
Lipoteichoic acid
n
https://t.me/med1917
378
Humans and bacteria are symbiotes, with each of us host to ten times as many
bacterial cells as our own human cells. Our gut, skin, and mucosal linings are
covered with bacteria. We rely on this for nutrition, functioning vitamin
inflammatory eects, and immune system regulation.
Bacterial disease results from a breach of the measures that limit bacteria to
their ‘normal’ roles: skin commensals moved into the bloodstream by a cannula,
antibiotics altering the commensal microflora, immune system evasion or dysfunction allowing organisms to stray beyond their usual boundaries, and toxin production. When treating infections we should therefore remember to look beyond the
oending organism and consider what factors may have aided pathogenesis: malnutrition, ‘barrier’ breach by cancer/ plastic, or immunosuppression.
See ‘Sepsis’, p
772
.
Bacterial glossary
Bacteria Prokaryotic micro- organism without a membrane- bound nucleus.
Classification of bacteria By microscopy and culture of infected samples.
Informs antibiotic choice. Includes:
• Gram stain: a staining technique. Bacteria with
thick, exposed peptidoglycan layers will stain
‘Gram positive’ (purple/ blue). Bacteria with a protected peptidoglycan layer will counterstain pink/
red and are ‘Gram negative’ (
• Shape: cocci = round; bacilli = rod- shaped; spiro-
chaete = spi ral.
• Aerobes/ anaerobes: some bacteria cannot survive
without oxygen (obligate aerobes), whilst others
cannot grow in its presence (obligate anaerobes).
Many more can survive in either environment (facultative anaerobes). Some types of infection are
more likely to involve aerobic or anaerobic bac-
GI inf ectio ns are typica lly a naerob ic.
teria, eg
Bacteraemia Bacteria circulating in the
bloodstream.
Bactericidal Kills bacteria both in and out of the
replication cycle.
Bacteriostatic Stops replication without killing existing bacteria.
Capsulate bacteria Bacteria with a thick outer capsule, eg Haemophilus
influenzae, Neisseria meningitidis, and Streptococcus pneumoniae. These are des-
troyed in the spleen. Following splenectomy (or splenic infarction, eg sickle cell
anaemia) there is an increased risk of infection by capsulate bacteria and prophylactic vaccination should be oered (
Commensal An organism that lives in/ on a host without causing harm.
Endotoxin A lipopolysaccharide complex found on the outer membrane of Gram-
negative bacteria. Can elicit an inflammatory response. Activates complement via
the alternative pathway.
Enterotoxin Exotoxin that targets the gut, eg Clostridium difficile toxin (p
Exotoxin Toxins secreted by bacteria acting at a site distant from bacterial
growth. Production of an exotoxin can determine virulence, eg botulinum, tetanus,
diphtheria, Shiga toxins.
Flagella A tail- like appendage that moves to propel the bacterium, eg Helicobacter
pylori.
Nosocomial Acquired in a hospital/ healthcare setting (pp
Obligate intracellular Bacteria that can only survive in host cells induce a cell-
mediated immune response and will not grow on standard culture media.
Ziehl– Neelsen stain Mycolic acid in the cell wall of mycobacteria resists Gram
staining but will appear red with acid- fast techniques (= acid- fast stain).
fig
K, anti-
Teichoic acid
9.3
).
p
403
Peptidoglycan
Cytoplasmic membrane
Lipopolysaccheride
Outer membrane
Peptidoglycan
Cytoplasmic membrane
Fig 9.
3
(a) Gram- positive versus
(b) Gram- negative cell membranes.
Reprinted by permission from
Macmillan Publishers Ltd: Nature
Reviews Microbiology, Cabeen et al.,
3(8
).
406– 7
),
601– 610
).
Porin
Nature Reviews
, copyright
Lipoprotei
Periplasm
Microbiology
407
2005
).
.
Antibiotics: action and resistance
Gl
V
T
P
Colisti
Te tracyclines
S subunit
s
in
olid
amphenicol
usidic acid
ase
Folate synthesis
Cell w
Fo
Nucleic acid
Protein synthesis
–lactams
P
Cephalosporins
Carbapenems
Ta
https://t.me/med1917
The antibiotic revolution began in
events (including a cancelled holiday and an unpredictable British summer) led to
Alexander Fleming’s observation that a contaminating Penicillium colony caused
lysis of staphylococci. Mass production and the ‘golden age’ of antibiotics followed, with the introduction of a variety of drugs selectively toxic to bacterial,
but not mammalian cells. This is achieved by:
• utilizing a target unique to bacteria, eg cell wall.
• selectively targeting bacterial- specific components, eg enzymes, ribosomes.
• preventing transport of the drug into human cells, eg metronidazole can only be
transported into anaerobic bacteria.
The mechanism of action of dierent classes of antibiotic is shown in
1928
when an extraordinary series of fortuitous
fig
9.4
.
379
all synthesis
enicillins
zobactam
sfomycin
ycopeptides
ancomycin
eicoplanin
olymyxins
n
Fig 9.
4
Classes of antibiotics and their bacterial cell targets.
This spectrum of available antibiotics revolutionized clinical practice and led to
the declaration: ‘It is time to close the book on infectious diseases, and declare the
war against pestilence won’ (attributed in urban legend to Dr William H Stewart,
US Surgeon General,
acity for a prokaryotic micro- organism to develop resistance far outstrips the
human capacity to develop new antibiotic drugs.
Antibiotic resistance can be:
• Intrinsic: due to inherent structural or functional characteristics, eg vancomycin
cannot cross the outer membrane of Gram- negative organisms.
• Acquired: bacteria have been evolving to resist antibacterial agents for billions of
years through mutation and/ or the transfer of resistance properties. This evolutionary phenomenon is accelerated by selection pressure from antibiotic use (including agriculture, aquaculture, and horticulture) which provides a competitive
advantage for mutated, resistant strains.
Resistance has emerged for all known antibiotics causing morbidity, mortality,
and a huge cost burden worldwide.
thetic, resistance cannot be acquired in nature, and yet it is epidemic.
Which brings us back to Alexander Fleming who, within
duction of his ‘miracle- mould’, gave this sage warning in his Nobel lecture of
‘Mr X has a sore throat. He buys some penicillin and gives himself, not enough
to kill the streptococci, but enough to educate them to resist penicillin. He then
infects his wife. Mrs X gets pneumonia and is treated with penicillin. As the
streptococci are now resistant to penicillin the treatment fails. Mrs X dies. Who is
primarily responsible for Mrs X’s death? Why Mr X, whose negligent use of penicillin changed the nature of the microbe.’
1965– 1969
Sulfamethoxazole
Trimethoprim
THF A
DHF A
PABA
50
S
30
S
30
S subunit
Aminoglycosides
). Such confidence failed to consider that the cap-
synthesis
DNA synthesis
Fluoroquinolones
Metronidazole
RNA polymer
Rifamycins
50
Clindamyc
Chlor
F
1 Misadventure is evident. Quinolones are syn-
2
years of the mass pro-
Macrolide
Linez
1945
9 Infectious diseases
,
9 Infectious diseases
Antibiotics
https://t.me/med1917
380
A guide to antibiotic prescribing
Give antibiotics immediately in patients with a systemic inflammatory response
to infection. See ‘Sepsis’,
Start smart
1 Do not prescribe2 antibiotics in the absence of clinical evidence of bacterial
infection, or for a self- limiting condition. Take time to discuss:
• why an antibiotic is not the best option
• alternative options, eg symptomatic treatment, delayed prescribing
• the views and expectations of the patient
• safety- netting advice: what the patient should do if their condition deteriorates.
2
Take microbiological samples before prescribing,1 especially for:
• hospital inpatients: review your prescription as soon as MC&S resul t is avai lable
• recurrent or persistent infection
• non- severe infection: consider if your prescription can wait for MC&S result s.
3
Follow local guidelines first, informed by local epidemiology and sensitivities.
4
Consider benefit and harm for each individual patient:
• Allergies: clarify the patient’s reaction— the true incidence of penicillin al-
lergy in patients who report that they are allergic is <
firmed penicillin allergy, cross- reactivity with
carbapenems is possible but rare (<
• Dose adjust for kidney function (usually creatinine clearance) and weight (ideal
body weight or ideal plus % excess weight in
• Check for medication interactions.
• In pregnancy and lactation, see p23.
5
Prescribe the shortest eective course. Most antibiotics have good oral avail-
ability. Use
IV antibiotics in line with local or national (sepsis) guidelines.
Then focu s
Review the clinical diagnosis and continuing need for antibiotics at 48h for all inpatients and all patients prescribed
• Stop antibiotics if there is no evidence of infection.
• Switch from IV to oral whenever possible.
• Change to a narrower spectrum antibiotic whenever possible.
• Continue regular clinical review whilst antibiotics are prescribed.
Antimicrobial stewardship
‘This will be a post- antibiotic era. In terms of new replacement antibiotics, the
pipeline is virtually dry... Prospects for turning this situation around look dim.’
While overall antibiotic usage deceased by 15% in England between
severe antibiotic resistant infections increased to approximately
die in Europe every year from antibiotic- resistant bacteria, ~
multidrug- resistant
counter in Egypt, India, and Pakistan. Antimicrobial resistance is a threat to public
health, economic development, and security. It is estimated that antibiotic resistance will cause up to
increase in healthcare costs.
Antimicrobial stewardship
• Monitoring, evaluation, and feedback on antimicrobial prescribing, bench- marked
against up- to- date local and national guidelines.
• Evalu ation of high/ low levels of prescribing, and prescribing outside of guidelines.
• Review of patient safety events: avoidable infection, drug reactions, complications
of antibiotic therapy, eg
• Education and dec ision support systems for antibiotic pres cribers.
• Antibiotic pack sizes that correspond to appropriate course lengths.
• Regular review of antimicrobial policy, treatment, and prophylaxis guidelines.
1
Clinical diagnosis of low- severity community- acquired pneumonia is an exception, see also UTI, p
p
772
.
10
%. In those with a con-
3
1
IV antibiotics:
TB. Cost is the only barrier to buying carbapenems over the
10
million deaths by
rd- generation cephalosporins and
%).
BMI
extr emes) : foll ow loca l guid ance.
Dr M Chan, Director- General of WHO, March
2017
148
per day. 25
500 000
/ year develop
2050
and lead to a $
100
trillion global
and
2012
2021
000
2 is necessary in all healthcare settings:
MRSA (p
384
), C. difficile (p
255
, p
407
).
292
.
.
,
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