ANTIBIOTICS AND INFECTIOUS DISEASES
CLINICAL USE OF ANTIBIOTIC THERAPY
GENERAL OVERVIEW
ANTIBIOTIC RESISTANCE
The antibiotics are miraculous drugs that have decreased the number of deaths related to infectious
diseases. However, in later years the number of deaths related to antibiotic resistance significantly
increase. Indeed, the number of patients who
died due to antibiotic resistance was of
1,270,000, while the number of patients in whom
antibiotic resistance was a contributor of death
was of 5 million. Therefore, the clinical use of
these drugs should be revised.
The critical pathogens list encompasses mostly
Gram-negative bacteria, which are hard to kill
due to their membrane structure. They are
divided into three main groups, which are:
• Critical priority: it encompasses
Acinetobacter baumannii, P.
aeruginosa, and Enterobacteriaceae (e
g. E. coli, E. faecium, etc.); all are
carbapenem-resistant.
• High priority: it encompasses E. faecium
(vancomycin-resistant), S. aureus
(MRSA), H. pylori (clarithromycin-resistant), and Salmonella spp. (fluoroquinolones resistant).
• Medium priority: it encompasses S. pneumoniae (penicillin-non-susceptible), H. influenzae
(ampicillin-resistant), and Shigella spp. (fluoroquinolone-resistant).
This means that most of them are resistance to first line antibiotics. In Italy, about 25%-50% of S.
aureus is methicillin resistant. The same percentage accounts for carbapenem-resistant
Enterobacterales (used in combination with colistin). Finally, more than 75% of Acinetobacter
baumannii are multidrug-resistant. The levels of carbapenem-resistant Enterobacteriaceae (CRE) and
A. baumannii have reached hyper-endemic levels, and together with MRSA, this situation causes Italy
to be one of the European countries with the highest level of resistance in Europe.
ANTIBIOTIC RESISTANCE IN THE FUTURE
The antibiotic resistance is not a recent phenomenon, but it started as soon as they were developed.
The problem is that now is more difficult and expensive to develop new antibiotics. Since 1990s no
novel antibiotics have been created,
and therefore while antibiotic
resistance has been increased the
number of functional antibiotics has
been decreased. According to the
Economist O’Neil in 2050 about 10
millions of people will die due to
antimicrobial resistance. Therefore, in the future there will be a change
in the healthcare system, since most of the hospital procedures require
antibiotics (e. g. organ transplantation, surgery, chemotherapy, treating
infections, etc.), and all of them should be revised. Moreover, there will
be a change in the way in which common infections are treated (e. g. LRT,
UTIs, etc.), with an increased in the number of mortality, as well as there
will be an increase in the maternal/child mortality.
,B – BUGS ASSOCIATED WITH PRESENTING SIGNS/SYMPTOMS
PATIENT’S MEDICAL HISTORY
The mnemonic BACTERIA-C is useful to determine and select the correct antibacterial and its right
posology. The B stands for bugs associated with the presenting signs/symptoms. The most important
tests for establishing the diagnosis of an infectious diseases are four, which are:
• Patient’s medical history: it accounts for about 75% of the diagnosis of infectious diseases; it
should be asked for the chief complaint, the other associated symptoms, the eight cardinal
descriptors (i. e. timing, location, character, aggravating factors, alleviating factors, associated
symptoms, severity, setting), the travel history, animal exposure, social factors, diets,
exposure, and host immune status.
• Patient’s physical exam: it may tell physician further information regarding patient’s status.
• Radiographic imaging: it provides additional information of what is occurring within the body.
• Laboratory (microbiological) studies: it finally determines the aetiological agent.
To better understand the importance of the patient’s medical history an example should be made. A
patient, 34y/o farmer from Sicily, has as chief complaint back pain after sitting for more than couple
of hours. This pain suggests that he has spondylitis. Normally,
spondylitis is caused by either Strep., Pseudomonas,
Enterobacter spp. (25%) or S. aureus or S. epidermidis (50%).
However, by looking to his medical history it is observed that the
patient is a cattle farmer who produces milk in Sicily. Therefore,
physician may suggest that spondylitis is caused by Brucella.
This hypothesis is reinforced by other symptoms (e. g. fever,
achy joints, headache, etc.). The brucellosis requires more
specific treatment and diagnostic testing, which are based on
blood culture, PCR, and serological studies. The treatment is
based on gentamycin, doxycycline, and rifampin, which is
completely different from the standard spondylitis regimens.
PHYSICAL EXAM, RADIOLOGY, AND LABORATORY TESTS
The common immunocompromising conditions are:
• Chronic diseases (e. g. T1D, COPD, etc.).
• Autoimmune diseases (e. g. SLE, rheumatoid arthritis, etc.)
• Genetic diseases (e. g. primary immunodeficiencies).
• Cancer and chemotherapy.
• Human immunodeficiency virus (HIV).
• Solid and organ or bone marrow transplant.
• Advanced age.
• Malnutrition.
• Chronic use of corticosteroids or other immunosuppressive medications.
• Chronic infections.
• Smoking.
The physical exam should account vital signs, lymphatics, skin exam (rashes, skin lesions, distal
extremities), foreign bodies, inspection, palpitation, percussion, and auscultation.
The radiology helps to distinguish among different possible pathogens. For instance, the cause of
pneumonia can be differentiated through a
chest X-ray. If there is a consolidation with air
bronchogram it is suspected bacterial
pneumonia, if it is interstitial, it may viral, while
if nodules are found it may be either fungal
pneumonia or TB.
, The clinical presentation may favour specific pathogen aetiology. For instance, cellulitis can be caused
by S. aureus, which is presented with pus and blisters. Conversely, the -haemolytic Streptococci
cause erysipelas which is more
erythematous. Another example is the
clinical manifestation of meningococcal
infection on the skin (e. g. rash), which is an
important early sign.
The most likely infectious aetiology depends
also on the type of infection and where it is
acquired. For instance, for LRT infection it
can be community-acquired (e. g. viral, S. pneumoniae, H. influenzae, etc.) or hospital-acquired (e. g.
K. pneumoniae, E. coli, P. aeruginosa, MRSA, etc.).
The laboratory tests are also essential to identify the aetiology of an infectious disease. There are
different culture that can be performed, from different specimens, such as blood, sputum, urine, and
CSF. The most important
aspect is that they should
be carried out before
starting antibiotic therapy
and that they should be
representative of the
signs/symptoms. Moreover, blood tests may help in identifying the aetiological agent.
A – ACTIVITY AT THE SITE OF INFECTION
VOLUME OF DISTRIBUTION (Vd)
The A of the BACTERIA-C stands for activity at the site of the infection. It means that an antibiotic
should be chosen based on the possibility of it to act on the site of infection. Therefore, the
pharmacology of the antimicrobial,
both pharmacokinetics and
pharmacodynamics should be
known.
The antibiotic pharmacokinetics are
described by concentration-time
curves in serum, and through this
graph different parameters can be
determined, such as the area under the curve (AUC), the peak, and the trough. The four phases of PK
are absorption, distribution, metabolism, and elimination.
Another pharmacokinetic parameter is the volume of distribution (Vd), which is the volume of fluid
that should be required to contain the total amount of administered drug at same concentration
observed in the plasma. The drugs can be
divided into two groups according to their
Vd, which are:
• High: Vd: they are lipophilic drugs,
which tend to concentrate in tissues
and fat (e. g. rifampicin, macrolides,
tetracyclines, sulphonamides,
fluoroquinolones, etc.).
• Low Vd: they are hydrophilic drugs,
with high protein binding; they tend
to concentrate in the bloodstream
and in the ECF (e. g. beta-lactam, aminoglycosides, etc.).
Typically, when the Vd>42-46L the drug is also accumulated in other sites, different from fluids.
CLINICAL USE OF ANTIBIOTIC THERAPY
GENERAL OVERVIEW
ANTIBIOTIC RESISTANCE
The antibiotics are miraculous drugs that have decreased the number of deaths related to infectious
diseases. However, in later years the number of deaths related to antibiotic resistance significantly
increase. Indeed, the number of patients who
died due to antibiotic resistance was of
1,270,000, while the number of patients in whom
antibiotic resistance was a contributor of death
was of 5 million. Therefore, the clinical use of
these drugs should be revised.
The critical pathogens list encompasses mostly
Gram-negative bacteria, which are hard to kill
due to their membrane structure. They are
divided into three main groups, which are:
• Critical priority: it encompasses
Acinetobacter baumannii, P.
aeruginosa, and Enterobacteriaceae (e
g. E. coli, E. faecium, etc.); all are
carbapenem-resistant.
• High priority: it encompasses E. faecium
(vancomycin-resistant), S. aureus
(MRSA), H. pylori (clarithromycin-resistant), and Salmonella spp. (fluoroquinolones resistant).
• Medium priority: it encompasses S. pneumoniae (penicillin-non-susceptible), H. influenzae
(ampicillin-resistant), and Shigella spp. (fluoroquinolone-resistant).
This means that most of them are resistance to first line antibiotics. In Italy, about 25%-50% of S.
aureus is methicillin resistant. The same percentage accounts for carbapenem-resistant
Enterobacterales (used in combination with colistin). Finally, more than 75% of Acinetobacter
baumannii are multidrug-resistant. The levels of carbapenem-resistant Enterobacteriaceae (CRE) and
A. baumannii have reached hyper-endemic levels, and together with MRSA, this situation causes Italy
to be one of the European countries with the highest level of resistance in Europe.
ANTIBIOTIC RESISTANCE IN THE FUTURE
The antibiotic resistance is not a recent phenomenon, but it started as soon as they were developed.
The problem is that now is more difficult and expensive to develop new antibiotics. Since 1990s no
novel antibiotics have been created,
and therefore while antibiotic
resistance has been increased the
number of functional antibiotics has
been decreased. According to the
Economist O’Neil in 2050 about 10
millions of people will die due to
antimicrobial resistance. Therefore, in the future there will be a change
in the healthcare system, since most of the hospital procedures require
antibiotics (e. g. organ transplantation, surgery, chemotherapy, treating
infections, etc.), and all of them should be revised. Moreover, there will
be a change in the way in which common infections are treated (e. g. LRT,
UTIs, etc.), with an increased in the number of mortality, as well as there
will be an increase in the maternal/child mortality.
,B – BUGS ASSOCIATED WITH PRESENTING SIGNS/SYMPTOMS
PATIENT’S MEDICAL HISTORY
The mnemonic BACTERIA-C is useful to determine and select the correct antibacterial and its right
posology. The B stands for bugs associated with the presenting signs/symptoms. The most important
tests for establishing the diagnosis of an infectious diseases are four, which are:
• Patient’s medical history: it accounts for about 75% of the diagnosis of infectious diseases; it
should be asked for the chief complaint, the other associated symptoms, the eight cardinal
descriptors (i. e. timing, location, character, aggravating factors, alleviating factors, associated
symptoms, severity, setting), the travel history, animal exposure, social factors, diets,
exposure, and host immune status.
• Patient’s physical exam: it may tell physician further information regarding patient’s status.
• Radiographic imaging: it provides additional information of what is occurring within the body.
• Laboratory (microbiological) studies: it finally determines the aetiological agent.
To better understand the importance of the patient’s medical history an example should be made. A
patient, 34y/o farmer from Sicily, has as chief complaint back pain after sitting for more than couple
of hours. This pain suggests that he has spondylitis. Normally,
spondylitis is caused by either Strep., Pseudomonas,
Enterobacter spp. (25%) or S. aureus or S. epidermidis (50%).
However, by looking to his medical history it is observed that the
patient is a cattle farmer who produces milk in Sicily. Therefore,
physician may suggest that spondylitis is caused by Brucella.
This hypothesis is reinforced by other symptoms (e. g. fever,
achy joints, headache, etc.). The brucellosis requires more
specific treatment and diagnostic testing, which are based on
blood culture, PCR, and serological studies. The treatment is
based on gentamycin, doxycycline, and rifampin, which is
completely different from the standard spondylitis regimens.
PHYSICAL EXAM, RADIOLOGY, AND LABORATORY TESTS
The common immunocompromising conditions are:
• Chronic diseases (e. g. T1D, COPD, etc.).
• Autoimmune diseases (e. g. SLE, rheumatoid arthritis, etc.)
• Genetic diseases (e. g. primary immunodeficiencies).
• Cancer and chemotherapy.
• Human immunodeficiency virus (HIV).
• Solid and organ or bone marrow transplant.
• Advanced age.
• Malnutrition.
• Chronic use of corticosteroids or other immunosuppressive medications.
• Chronic infections.
• Smoking.
The physical exam should account vital signs, lymphatics, skin exam (rashes, skin lesions, distal
extremities), foreign bodies, inspection, palpitation, percussion, and auscultation.
The radiology helps to distinguish among different possible pathogens. For instance, the cause of
pneumonia can be differentiated through a
chest X-ray. If there is a consolidation with air
bronchogram it is suspected bacterial
pneumonia, if it is interstitial, it may viral, while
if nodules are found it may be either fungal
pneumonia or TB.
, The clinical presentation may favour specific pathogen aetiology. For instance, cellulitis can be caused
by S. aureus, which is presented with pus and blisters. Conversely, the -haemolytic Streptococci
cause erysipelas which is more
erythematous. Another example is the
clinical manifestation of meningococcal
infection on the skin (e. g. rash), which is an
important early sign.
The most likely infectious aetiology depends
also on the type of infection and where it is
acquired. For instance, for LRT infection it
can be community-acquired (e. g. viral, S. pneumoniae, H. influenzae, etc.) or hospital-acquired (e. g.
K. pneumoniae, E. coli, P. aeruginosa, MRSA, etc.).
The laboratory tests are also essential to identify the aetiology of an infectious disease. There are
different culture that can be performed, from different specimens, such as blood, sputum, urine, and
CSF. The most important
aspect is that they should
be carried out before
starting antibiotic therapy
and that they should be
representative of the
signs/symptoms. Moreover, blood tests may help in identifying the aetiological agent.
A – ACTIVITY AT THE SITE OF INFECTION
VOLUME OF DISTRIBUTION (Vd)
The A of the BACTERIA-C stands for activity at the site of the infection. It means that an antibiotic
should be chosen based on the possibility of it to act on the site of infection. Therefore, the
pharmacology of the antimicrobial,
both pharmacokinetics and
pharmacodynamics should be
known.
The antibiotic pharmacokinetics are
described by concentration-time
curves in serum, and through this
graph different parameters can be
determined, such as the area under the curve (AUC), the peak, and the trough. The four phases of PK
are absorption, distribution, metabolism, and elimination.
Another pharmacokinetic parameter is the volume of distribution (Vd), which is the volume of fluid
that should be required to contain the total amount of administered drug at same concentration
observed in the plasma. The drugs can be
divided into two groups according to their
Vd, which are:
• High: Vd: they are lipophilic drugs,
which tend to concentrate in tissues
and fat (e. g. rifampicin, macrolides,
tetracyclines, sulphonamides,
fluoroquinolones, etc.).
• Low Vd: they are hydrophilic drugs,
with high protein binding; they tend
to concentrate in the bloodstream
and in the ECF (e. g. beta-lactam, aminoglycosides, etc.).
Typically, when the Vd>42-46L the drug is also accumulated in other sites, different from fluids.
