This document discusses antibiotics and their use in the intensive care unit (ICU). It begins by defining key terms like infection, SIRS, sepsis, severe sepsis, and septic shock. It then discusses the most common causes of infections in the ICU, including devices, nursing care, and antibiotic overuse. The most frequent infectious organisms in the ICU are noted as gram-positive bacteria like coagulase-negative staphylococci and Candida species. Factors predisposing patients to infection and approaches for diagnosis and empiric antibiotic therapy are also summarized.

1. Antibiotics
uses in ICU
Dr.Radhwan Hazem Alkhashab
Consultant anaesthesia & ICU
2021

2. 1. Definitions.
2. Determine the most common causes of infections in ICU.
3. How to assess the patient suffering from infection.
4. Choice the appropriate antibiotic.
Goals of lecture

3.  Infection: The invasion and multiplication of microorganisms such as bacteria, viruses, and
parasites that are not normally present within the body.
 SIRS: (abandoned since 2016) is nonspecific and can be caused by ischemia, inflammation,
trauma, infection, or several insults combined:
1) Fever of more than 38°C or less than 36°C.
2) Heart rate of more than 90 beats per minute.
3) Respiratory rate of more than 20 breaths per minute or arterial carbon dioxide tension (PaCO 2)
of less than 32 mm Hg.
4) Abnormal white blood cell count (>12,000/µL or < 4,000/µL or >10% immature [band] forms.
 Sepsis: a suspected or documented source of infection plus two or more SIRS criteria .
Definitions

4.  Severe sepsis: sepsis with acute sepsis-induced organ
dysfunction of one or more organ systems
 MOD: severe pain associated with failure of at least two
of the following organs: liver, lung, and kidney.
 Septic shock: a subset of severe sepsis syndrome in
which the organ dysfunction is
cardiovascular, that is, a subset of severe sepsis in which
there is cardiovascular dysfunction.
Specifically, sepsis-induced hypotension (mean arterial
pressure [MAP] <65 mm Hg) that persists despite
adequate and aggressive volume resuscitation. Patients
will often require vasopressors to keep MAP 65 mm Hg.

5.  SOFA (Sequential Organ Failure Assessment ) which includes:
1. Respiratory system - The ratio of arterial oxygen tension to fraction of inspired oxygen
(PaO 2/FiO 2).
2. Cardiovascular system - Mean arterial pressure (MAP) and presence of vasopressor
medication(s).
3. Hepatic system - Bilirubin level.
4. Coagulation system - Platelet concentration.
5. Neurologic system - Glasgow Coma Score.
6. Renal system - Serum creatinine or urine output

6. Infections are frequently suspected or documented in ICU,& hence this is consider the major causes
of morbidity & mortality in ICU. Patients hospitalized in ICUs are 5 to 10 times more likely to acquire
nosocomial infections than other hospital patients.
The problem of antimicrobial resistance has increased significantly in the past decade. A number of
factors magnify this problem in the intensive care unit (ICU). These includes:
1. Long term uses of invasive devices.
2. Bad nursing care
3. Loss of skin barrier in surgical wounds
4. Non logic uses of antimicrobial agents.
5. Uses of respiratory supportive therapy.
Antimicrobial resistance is a greater urgency for those multidrug-resistant organisms for which only
a few antibiotic alternatives remain, such as vancomycin-resistant Enterococci and carbapenem-
resistant Acinetobacter baumannii.
Introduction

7. A recent study of nosocomial bloodstream infections found the following infecting organisms in
the intensive care unit (ICU):
1. Gram positive (65%): coagulase-negative staphylococci (36% of isolates), Staphylococcus
aureus (17%), enterococci (10%).
2. Gram negative (25%): Escherichia coli (4%), Klebsiella sp. (4%), Pseudomonas aeruginosa
(5%), Enterobacter sp. (5%), Serratia sp. (2%), Acinetobacter sp. (2%).
3. Fungi (9%): primarily Candida species (albicans 54%, glabrata 19%, parapsilosis 11%,
tropicalis 11%).
Which microorganisms are most commonly
associated with sepsis?

8. Severe infection is a common cause of admission to intensive care. Both patient
and environmental factors account for this increased susceptibility.
Common sites for infection in critically ill patients are:
• The chest.
• Intravascular catheters (‘line sepsis’).
• Bacteremia, unknown source.
• Wounds/drains.
• The urinary tract.
• Intra-abdominal.
 The term nosocomial infection describes hospital acquired infections that develop at least 48 h
following admission. The reported incidence of nosocomial infections in ICU patients has
ranged between 10% and 50%,
Infection in critically ill individuals

9. 1. Intubation and ventilation, as a result of cough suppression (due to necessity for sedation),
repeated tracheal suction, and microaspiration of (infected) oropharyngeal contents.
2. Impaired airway protection, due to dysfunction of the central nervous system, drugs, and
nasogastric tube.
3. Surgical factors predisposing to infection in the critically ill patient.
4. Chronic obstructive pulmonary disease.
5. Antibiotic therapy.
6. Severe underlying disease.
7. Immunosuppression.
8. Malnutrition.
9. Raised gastric pH (bacterial overgrowth of stomach).
Predisposing factors to infection

10. The clinical features used to diagnose infection in ICU is based on the underlying pathology for example
Hospital-acquired pneumonia (HAP)& ventilator-associated pneumonia (VAP) (e.g, fever, leukocytosis,
purulent sputum production, and new infiltrates on a chest X-ray, real-time PCR assays).
Other investigations:
1. C-reactive protein (CRP).
2. Procalcitonin (PCT).
3. Several cytokines, and cell surface markers.
4. Urine culture.
5. Rapid-detection assay to identify MRSA from wound specimens.
6. Detection of the antigens of Streptococcus pneumoniae.
7. Legionella pneumophila serogroup 1 in urine
Diagnosis

11. Anti-microbial agents may be used in the following ways:
• Prophylactic – to prevent an infective complication
• Empiric – to treat suspected infection before culture results are available
• Targeted – to treat established infection demonstrated by culture
Infection is only one of a number of causes of pyrexia in the intensive care unit setting, It is
particularly worth bearing in mind that drug fever is commonly caused by antibiotics and results in
a pyrexia.
Empiric therapy should be reserved for those patients with well-defined signs and symptoms of
infection where delay in therapy would be expected to be harmful. It is essential to obtain
appropriate specimens for microbiological examination before starting empiric therapy.
The choice of agent(s) is also dependent on knowledge of the organisms likely to be involved
Antibiotic therapy

12. Non-infective causes of pyrexia

13. 1- Site of infection.
2- Patient factors.
Renal
Hepatic.
Immune system.
Age.
3-Safety of antibiotics.
4-Cost of therapy.
Guidelines empirical antibiotic therapy

14. Nosocomial bacteremia are associated with the following primary sources of infection.
 Intravascular catheters.
 Pneumonia .
 Urinary tract.
 Wounds/drains.
 Intra-abdominal.
 Endocarditis
called ‘line sepsis’ is particularly common with central venous catheters, especially when
inserted in less than optimal conditions (e.g, as an emergency in the resuscitation room), if the
placement is difficult and/or performed by an inexperienced operator, and when placed in the
femoral vein.
Nosocomial bacteremia

15. Intensive care units have long been associated with an increased prevalence of antibiotic-resistant
organisms compared with other areas of the hospital,
The propagation of antibiotic-resistant microorganisms
1. The frequent use of broad-spectrum antibiotics.
2. Patient population with prolonged lengths of stay.
3. Need for invasive devices.
4. Close interactions between health care workers and critically ill patients.
Antibiotic Resistance in the ICU

16. The dose of an antibacterial varies according to a number of factors including:
1. Age.
2. Weight.
3. Hepatic function.
4. Renal function.
5. Severity of infection.
The route of administration of an antibacterial often depends on the severity of the infection.
Life-threatening infections require intravenous therapy. Antibacterial that are well absorbed may be
given by mouth even for some serious infections.
Dose & route of administration

17. The resistant organisms seen most commonly in the ICU include methicillin-resistant S. aureus
(MRSA), vancomycin resistant Enterococcus faecium or E. faecalis , and multidrug– resistant gram-
negative bacilli, such as P. aeruginosa, Stenotrophomonas maltophilia, and extended-spectrum β-
lactamase–producing Enterobacteriaceae. Patients either can enter the ICU with endogenous
resistant bacteria already present or can become colonized during their ICU stay owing to cross-
contamination from other colonized patients. In active surveillance, cultures are obtained for the
specific purpose of identifying colonized patients. These cultures can be performed on every patient
or on selected high-risk subsets.

18. Inadequate initial antibiotic therapy of infections has been associated with increased mortality
among ICU patients. However, the increasing use of broad-spectrum antibiotics has been associated
with the antibiotic-resistant pathogens. Exposure to broad-spectrum antibiotics can alter the
normal flora of patients and can facilitate colonization with resistant organisms.
Antibiotic use & control

19. Beta lactum:
These are a broad class of antibiotics that contain a beta lactum ring in their molecular structure.
E.g. Pencillins , Cephalosporins , Carbapenums.
Beta lactum antibiotics are the most widely used group of antibiotics
--Bacteria often develop resistance by synthesizing a beta lactumase , an enzyme that attacks beta
lactum ring.
--To overcome this resistance these antibiotics are prescribed with the beta lactum inhibitors.
Main antibiotic used in ICU

20. Natural penicillins:
1. Benzyl penicillins
2. Phenoxymethylpenicillins
Semisynthatic penicillins:
1-Antistaphylococci penicillinase resistant penicillins. e.g. Oxacillin, dicloxacillin,methacillin.
2-Antipseudomonius penicillins , e.g. Piperacillins.
3-Wide spectrum , e.g. Ampicillin, amoxicillins.
Pencillins

21. Beta lactamase inhibitors:
 Clavulanic acid.
 Sulbactam.
 Tazobactam.
Beta lactamase protected:
● Amoxicillin / clavulanate.
● Ampicillins / sulbactam.
● Ticarcillin / clavulanate.
● Piperacillin / tazobactam.

22. Cephalosporins
1st Generation :-
● Cephazolin
● Cephalothin
● Cephaloridine
2nd Generation:-
● Cefamycin
● Cefoxitin
● Cefotitan
● Cefmetazole
3rd Generation:-
● Ceftriaxone
● -Cefotaxime
● -Ceftazidime
4th Generation:-
● Cefepime
● -Cefpirome

23. Act by inhibiting the cell wall synthesis against gram negative infection.
 Imipenum
 Meropenum
 Doripenum.
Carbapenums

24. Exert their antibacterial effect by preventing bacterial DNA from duplication
● Ciprofloxacin
● Levofloxacin
● Ofloxacin
● Pazufloxacin
● Moxifloxacin
Flouroquinilones

25. The mechanism of action of macrolides is inhibition bacterial protein biosynthesis.
This action is bacterostatic:
Classification:
1- Natural substances: e.g. Erythromycin.
2- Semisynthetic: e.g. clarithromycin.
3- Azalide: e.g. Azithromycin.
Macrolides

26. Mainly gram negative bactericidal agent work by inhibiting protein biosynthesis.
1st Generation:
Streptomycin , neomycin ,kenamycin.
2nd Generation:
Gentamycin, tobramycin.
3rd Generation:
Amikacin, netilmicin.
Aminoglycosides

27. These drugs inhibit the synthesis of cell wall.
Due to toxicity their use is restricted to patients who have hypersensitive to beta lactums.
Effective mainly against gram positive cocci, e.g. Vancomycin, Teicoplanin.
Glycopeptides

28. Action spectrum gram negative bacteria including (Citrobacter spp, Enterobacter spp,
Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus
mirabilis, Pseudomonas aeruginosa, Serratia marcescens).
Clinical uses : sepsis, UTI, meningitis.
Types :
 Azactam.
 Aztreonam.
 aztreonam inhalation.
 Cayston
Monobactum

29.  According to activity:
1-Bactericidal :they kill bacteria directly, e.g. Beta lactums , Cephalosporins , Carbapenums
aminoglycosides.......
2-Bacteriostatic: they stop bacteria from growing
Ex- Tetracycline, chloramphenicol, sulphonamides, macrolides, lincosamides
Classification of antibiotics

30.  According to spectrum:
1-Broad spectrum: They work against variety of bacteria e.g. penicillin, carbapenums,
fluoroquinolones, cephalosporin.
2-Narrow spectrum : They work against a small range of bacteria, e.g. macrolides , lincosamides,
glycopeptides.
Classification of antibiotics

31.  According to mechanism of action:
1-Cell wall synthesis inhibitors: e.g. penicillins , beta lactums , cephalosporins , carbapenums ,
macrolides & vancomycin.
2- Protein synthesis inhibitors :e.g. Aminoglycosides , macrolides , tetracycline , chloramphenicol ,
clindamycin , linezolid.
3- DNA synthesis inhibitors : e.g. floroquinolones , metronidazole.
4- RNA synthesis inhibitors: e.g. rifampicin.
5- Folic acid synthesis inhibitors: e.g. sulphonamides , trimethoprim.

32. Empirical antibiotic uses according to site of
infection
CNS
Meningitis;
Ceftriaxone- 2 gm IV q12h
+
Vancomycin- 500-750 mg IV q6h
Alternative
Meropenum 2gm IV q8h
Post head trauma:
Cefepime 2gm IV q8h
+
Vancomycin 500-750mg IV q6h
Alternative:
Meropenum 2g IV
Q8h, vancomycin(1g IV q6-8h)

33. Pneumonia:
Community acquired: ceftriaxone 1g IV q12h + Azithromycin 500mg IV q24h.
Hospital acqiured : imipenum 500mg IV q6h, or meropenum- 1g IV q8h
Or Doripenum 500mg IV q8h + levofloxacillin 750mg IV q 24h, or moxiflox 400mg IV q24h.
Aspiration pneumonia:
-Pipercillin + tazobactum 4.5gm IV q8h
Alternative: ceftriaxone 1g IV q12h + metronidazole 500mg IV q8h.

34. Peritonitis:
Perforation peritonitis:
Pipercillin+Tazobactum 4.5g IV q8h, or ertapenum 1g IV 124h
Life threatening peritonitis
Imipenum 500mg IV q8h, or meropenum 1g IV q8h , or doripenum 500mg IV q8h.
Bone & joint infections:
Flucloxacillin 2g IV q8h, if allergic to penicillins give Cefuroxime 2g IV q8h , or Clindamycin
600mg IV q6h.
If MARSA is possible give: Pipercillins+ Tazobactum 4.5g IV q8h + Vancomycin 1g IV q8h

35. ● VAP is a common nosocomial infection occurring in ICU patients receiving mechanical
ventilation for > 48 hours. mortality is in the order of 30%.
Aerobic Gram-negative bacilli colonize the oropharynx and upper GI tract (augmented by the
use of H2-receptor antagonists) and these pathogens gain access to the lungs with movement
aided by the positive pressure of mechanical ventilation.
● Diagnosis :Sampling of sputum obtained from the distal areas of the respiratory tract using
techniques that prevent contamination with the resident flora of the trachea and major bronchi
helps distinguish between colonization and true infection.
Such methods include:
• Protected specimen brushing (where >1,000 colony-forming units/ml suggests infection)
• Bronchoalveolar lavage (>10,000 colony-forming units/mL suggests infection).
Patients with suspected VAP should have a lower respiratory tract specimen cultured via one
of the above techniques or via endotracheal aspiration prior to administering new antimicrobial
therapy.
Ventilator-Associated Pneumonia (VAP)

36. Treatment: is timely administration of appropriate antibiotics and preventative measures
include scrupulous hand washing, good oral hygiene, nursing the patient semi-recumbent,
ensuring adequate tracheal cuff inflation, improved cuff design, supraglottic suction, the
rational use of H 2-receptor antagonists, avoiding the need for re-intubation where possible .

37. Way of prevention of infection in ICU
1. Take precautions
Before you begin cleaning a hospital, it’s vital that you protect yourself and your team. Always
wear personal protective equipment (PPE), such as gloves, masks, or safety glasses.
2. Use quality disinfectant
These powerful chemicals kill 99% of germs found in hospitals almost on contact.
3. Properly dispose of sharps.
4. Personal sterilization : hand washing and antisepsis (hand hygiene); use of PPE when
handling blood, body substances, excretions and secretions;; prevention of needle
stick/sharp injuries; environmental cleaning and spills-management; and appropriate
handling of waste.

38. Prevention of VAP:

39. Prevention of VAP

40. THANK YOU