Case Presentation # 1- Establishing Presence of Infection

R.G., a 63-year-old, 70-kg man in the intensive care unit, underwent

emergency resection of his large bowel. He has been mechanically
ventilated throughout his postoperative course. On day 20 of his hospital stay,
R.G. suddenly becomes confused; his blood pressure (BP) drops to 70/30
mm Hg, with a heart rate of 130 beats/minute. His extremities are cold to
the touch, and he presents with circumoral pallor.
His temperature increases to 40◦C (axillary), and his respiratory rate
is 24 breaths/minute.
Copious amounts of yellow-green secretions are suctioned from his
endotracheal tube.
Physical examination reveals sinus tachycardia with no rubs or
murmurs. Rhonchi with decreased breath sounds are observed on
auscultation.
The abdomen is distended, and R.G. complains of new abdominal pain.
No bowel sounds can be heard, and the stool is guaiac positive.
Urine output from the Foley catheter has been 10 mL/hour for the past 2 hours.
Erythema is noted around the central venous catheter.
A chest radiograph demonstrates bilateral lower lobe infiltrates, and
urinalysis reveals >50 white blood cells/high power field (WBC/HPF),
few casts, and a specific gravity of 1.015. Blood, endotracheal aspirate, and
urine cultures are pending.

Other laboratory values include the following:

Sodium (Na), 131 mEq/L (normal, 135 to 147) LOW
Potassium (K), 4.1 mEq/L (normal, 3.5 to 5) Normal
Chloride (Cl), 110 mEq/L (normal, 95–105) HIGH
CO2, 16 mEq/L (normal, 20–29 mEq/L) LOW
Blood urea nitrogen (BUN), 58 mg/dL (normal, 8–18) HIGH
Serum creatinine (SCr), 3.8 mg/dL (increased from 0.9 mg/dL at admission;
normal, 0.6–1.2) HIGH
Glucose, 320 mg/dL (normal, 70–110) HIGH
Serum albumin, 2.1 g/dL (normal, 4–6) LOW
Hemoglobin (Hgb), 10.3 g/dL LOW
Hematocrit (Hct), 33% (normal, 39%–49% [male patients]) LOW
WBC count, 15,600/μL with bands present (normal, 4,500–10,000 μL) HIGH –
soldier of the body
Platelets, 40,000/μL (normal, 130,000–400,000) LOW
Prothrombin time (PT), 18 seconds (normal, 10–12) LOW
Erythrocyte sedimentation rate (ESR), 65 mm/hour(normal, 0–20) HIGH
Procalcitonin, 1 mcg/L (normal <0.25mcg/L) HIGH

R.G.’s medical history includes temporal arteritis and seizures chronically

treated with corticosteroids and phenytoin.
Perioperative “stress doses” of hydrocortisone recently were administered
because of his surgical procedure. A Gram stain of R.G.’s tracheal aspirate
shows gram-negative bacilli.

 Circumoral pallor- The area around the mouth may appear pale
 Large bowel resection - is surgery to remove all or part of your large
bowel. This surgery is also called colectomy. The large bowel is also
called the large intestine or colon. During the procedure, the intestines,
bladder, or blood vessels near the bowels may become damaged.
Leakage: If the resection doesn’t heal properly or becomes infected, the
colon can leak. Doctors call this an anastomotic leak. It can lead to
bleeding and a dangerous infection.
 Normal axillary temperature: 36.3- 37.8 C
 Normal respiration rates for an adult person at rest range from 12 to 16
breaths per minute.
(https://www.google.com/amp/s/www.hopkinsmedicine.org/health/condi
tions-and-diseases/vital-signs-body-temperature-pulse-rate-respiration-
rate-blood-pressure%3famp=true)
 The secretions from the endotracheal tube should be white or clear. If
they start to change color, (e.g. yellow, brown or green) this may be a
sign of infection.
(https://www.hopkinsmedicine.org/tracheostomy/living/suctioning.html)
 Sinus tachycardia is a regular cardiac rhythm in which the heart beats
faster than normal. While it is common to have tachycardia as a
physiological response to exercise or stress, it causes concern when it
occurs at rest.

( Henning A, Krawiec C. Sinus Tachycardia. [Updated 2021 Aug 11]. In:

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022
Jan-. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK553128/)
 Murmurs are produced by blood flow turbulence and are more prolonged
than heart sounds; they may be systolic, diastolic, or continuous. They
are graded by intensity and are described by their location and when they
occur within the cardiac cycle. Murmurs are graded in intensity on a scale
of 1 to 6 .
 Rubs are high-pitched, scratchy sounds often with 2 or 3 separate
components, which may vary according to body position; during
tachycardia, the sound may be almost continuous.
 A distended abdomen is abnormally swollen outward.( appears
bloated). You can see and measure the difference, and sometimes you
can feel it. A distended abdomen can be due to bloating from gas, or it
can be due to accumulated fluid, tissue, or digestive contents.
 Foley catheter is a flexible tube that a clinician passes through the
urethra and into the bladder to drain urine.
 Erythema in central venous catheter- is a type of skin rash caused
by injured or inflamed blood capillaries around the area of insertion sa
catheter.
 Temporal Arteritis is inflamed blood vessels in the temporal.
 Seizure is a sudden, uncontrolled electrical disturbance in the brain.
 Band cells are an immature form of neutrophils, which are the most
commonly produced white blood cell. They are essential for fighting
disease. That’s why your body produces them in excess during an
infection. A normal band cell count is 10 percent or less.
 Inoculum is a biological material used for inoculation, the process of
introducing biological material, such as cells added to start a microbial
culture.
 Serratia marcescens - Well-documented infections caused by S.
marcescens include pneumonia, urinary tract infection, bacteremia,
biliary tract infection, wound infection, meningitis, and endocarditis.
 Carbapenems, among the beta-lactams, are the most effective against
Gram-positive and Gram-negative bacteria presenting a broad spectrum
of antibacterial activity. Their unique molecular structure is due to the
presence of a carbapenem together with the beta-lactam ring.
 In SEPSIS, IV drug is preferred over oral drugs because drug
absorption, distribution, metabolism and elimination are all altered in
sepsis even when organ failure is not apparent.
 Minimum inhibitory concentrations (MICs) are defined as the lowest
concentration of an antimicrobial that will inhibit the visible growth of a
microorganism after overnight incubation, and
 minimum bactericidal concentrations (MBCs) as the lowest
concentration of antimicrobial that will prevent the growth of an organism
..
 Depot delivery offers the advantage of a very high loading, controlled
release of drug for an extended period of time and reduces frequency of
dosing. The increase in AUC and decrease in Cmax reflects that the depot
formulations could reduce the toxic complications and limitations of
conventional and oral therapies.
 In addition, aminoglycosides have demonstrated persistent suppression
of bacterial growth after short exposure, a response referred to as the
post-antibiotic effect.
 Nephrotoxicity induced by aminoglycosides manifests clinically as
nonoliguric renal failure, with a slow rise in serum creatinine and a
hypoosmolar urinary output developing after several days of treatment.
 Nephrotoxicity is defining as rapid deterioration in the kidney
function due to toxic effect of medications and chemicals.
 PERIOPERATIVE- encompasses all three phases, before, during and
after surgery.

 BIOAVALABILITY- fraction of an administered drug that reaches the

systemic circulation.

 TACHYPNEA -rapid breathing, present in the patient Kay respiratory rate

niya is 24 BPM nya normal is 12-16.

 WBC /HIGH POWER FIELD: Normal: 0 – 5 per hpf. • Men usually have
< 2/hpf; women usually have < 5/hpf. – Presence of elevated WBCs
indicates the body may. Be fighting infection in the urinary tract.

 According to KDIGO, acute renal failure can be diagnosed if any one of

the following is present: An increase in SCr by 0.3 mg/dL or more within
48 hours. An increase in SCr of at least 150 percent within a seven-day
period. A urine volume of less than 0.5 ml/kg/h over a six-hour
period.Sep 19, 2021

 Procalcitonin (PCT), a protein that consists of 116 amino acids, is the

peptide precursor of calcitonin, a hormone that is synthesized by the
parafollicular C cells of the thyroid and involved in calcium homeostasis.
Procalcitonin arises from endopeptidase-cleaved preprocalcitonin.
Questions:
1.Which of R.G.'s signs and symptoms are consistent with infection?

SIGNS of an infection1
● Body temperature over 38 or under 36 degrees Celsius.
● Heart rate greater than 90 beats/minute
● Respiratory rate greater than 20 breaths/minute or partial pressure
of CO2 less than 32 mmHg
● Leucocyte count greater than 12000 or less than 4000 /microliters or
over 10% immature forms or bands.

SYMPTOMS of an infection2

● Fever (this is sometimes the only sign of an infection).

● Chills and sweats.
● Change in cough or a new cough.
● Sore throat or new mouth sore.
● Shortness of breath.
● Nasal congestion.
● Stiff neck.
● Burning or pain with urination.
● Unusual vaginal discharge or irritation.
● Increased urination.
● Redness, soreness, or swelling in any area, including surgical wounds and
ports.
● Diarrhea.
● Vomiting.
● Pain in the abdomen or rectum.
● New onset of pain.

In this case, the patient has shown a temperature of 40° C. By axillary

measurement it means the patient has fever .He also complains of abdominal
pain. His WBC is also high and lastly the patient’s chest radiograph shows the
presence of copious amounts of yellow–green secretions from his
endotracheal tube, and the erythema surrounding his central venous
catheter is also compatible with one or more infectious processes .
References:
1
Chakraborty, R. K. (2021, July 28). Systemic inflammatory response
syndrome. StatPearls [Internet]. Retrieved March 15, 2022, from
https://www.ncbi.nlm.nih.gov/books/NBK547669
2
Centers for Disease Control and Prevention. (2021, September 15). Know the
Signs and Symptoms of Infection. Retrieved March 15, 2022, from
https://www.cdc.gov/cancer/preventinfections/symptoms.htm#:%7E:text=Call
%20your%20doctor%20right%20away%20if%20you%20notice%20any
%20of,throat%20or%20new%20mouth%20sore.

2. What signs and symptoms manifested by R.G. are consistent with a

serious systemic infection?

Criteria for systemic infection Patient’s signs and symptoms

Temperature below 36°C or above Axillary temperature increases to

40°C
38°C

Heart rate greater than 90 Heart rate is 130 beats/minute

beats/minute

Respiratory rate above 20 Respiratory rate is 24 breaths/minute

breaths/minute, or arterial partial
pressure of carbon dioxide less than
32 mm Hg

White blood cells count less than 4 × White blood cell count is 15,600
microliter with bands present
109/L (4 000 mcL) or greater than 12
× 109/L (12 000 mcL), or more than
 10% bands.

Hypotension Blood pressure drops to 70/30 mmHg

:
Severe infections, may also lead to a loss of urine output by causing the body
to go into shock. This state of shock reduces blood flow to organs such as the
kidneys. The kidneys cannot make urine without this blood flow. Urine output of
less than 30 mL/hr (roughly 0.5 mL / kg / hour for a 70-kilogram patient)
should be considered cause for concern.1 The patient’s urine output from the
Foley catheter has been 10 mL/hour for the past 2 hours. 1

The patient’s procalcitonin level is high. If the results show a high

procalcitonin level, it’s likely to have a serious bacterial infection such as
sepsis.2

1Medical News Today (2019). Low urine output. Retrieved from

https://www.medicalnewstoday.com/articles/325398
2Medline Plus (2020). Procalcitonin test. Retrieved from
https://medlineplus.gov/lab-tests/procalcitonin-test/

C., & Duggal, A. (2020). Sepsis and septic shock: guidelines and management.
Cleveland Clinic Journal of Medicine, 87(1), 53-64.
https://www.ccjm.org/content/87/1/53

3. What medications or disease states confuse the diagnosis of

infection?

● An increased WBC count is associated with a variety of factors, including

major surgery, acute myocardial infarction, and the initiation of
corticosteroid therapy. Unlike infection, however, these disease states or
drugs do not cause a shift to the left. The patient's stress dose of
hydrocortisone, as well as his recent surgical procedure, may have
 contributed to his elevated WBC count. The presence of bands, on the
other hand, strongly suggests a bone marrow response to an infectious
process in this patient.
● Corticosteroids have the ability to mimic or mask infection.
Corticosteroids are associated with an increased WBC count and glucose
intolerance when starting therapy or increasing doses. Furthermore, some
patients experience corticosteroid-induced mental status changes that may
be similar to those seen in sepsis. Although corticosteroids can mimic
infection, they can also mask infection.
● Fever is also a common symptom of autoimmune diseases such as
systemic lupus erythematosus and temporal arteritis. Cancers such as
leukemia and lymphoma can also present with low-grade fevers similar to
those seen in an infectious process.

Reference:
Mayoclinic (2021). Infectious diseases. Retrieved from
https://www.mayoclinic.org/diseases-conditions/infectious-diseases/diagnosis-
treatment/drc-20351179

4. What are the most likely sources of R.G.’s infection?

R.G. has a number of potential infection sites The presence of pneumonia

is suggested by the presence of yellow-green sputum, tachypnea, and an
altered chest radiograph. 1 The abdominal pain, absence of bowel sounds, and
recent surgical procedure, on the other hand, point to an intra-abdominal
source. Finally, the abnormal urinalysis (>50 WBC/HPF) and erythema around
the central venous catheter point to urinary tract and catheter infections,
respectively. 2

Reference:
1
Justina Gamache, M. D. (2022, January 25). Bacterial pneumonia. Practice
Essentials, Background, Pathophysiology. Retrieved March 15, 2022, from
https://emedicine.medscape.com/article/300157-overview

2
Patterson, J. W. (2021, July 14). Acute abdomen. StatPearls [Internet].
Retrieved March 15, 2022, from
https://www.ncbi.nlm.nih.gov/books/NBK459328/
5. What are the most likely pathogens associated with R.G.’s
infection(s)?

The patient has several potential sources of infection, all of which are likely to
be pathogens.

Respiratory Tract 1
Most upper respiratory infections are of viral etiology.
● Epiglottitis and laryngotracheitis are exceptions with severe cases likely
caused by Haemophilus influenzae type b.
● Bacterial pharyngitis is often caused by Streptococcus pyogenes.
● The most common bacterial agents responsible for acute sinusitis are
Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
catarrhalis.

Causative agents of lower respiratory infections are viral or bacterial.

Viruses cause most cases of bronchitis and bronchiolitis.
● In community-acquired pneumonias, the most common bacterial agent is
Streptococcus pneumoniae.
● Atypical pneumonias are caused by such agents as Mycoplasma
pneumoniae, Chlamydia spp, Legionella, Coxiella burnetii and viruses.
● Nosocomial pneumonias and pneumonias in immunosuppressed patients
have protean etiology with gram-negative organisms and staphylococci as
predominant organisms.

Urinary Tract 2
● Most urinary infections are caused by bacteria from the intestinal flora.
Eschericia coli causes about 70 percent of all infections. Staphylococcus
saprophyticus causes about 10 percent of infections in young women.
● Pseudomonas aeruginosa, Serratia marcescens, Enterococcus faecalis,
and Staphylococcus epidermidis are common hospital-acquired
pathogens.
● Yeasts and, in some parts of the world, protozoa are occasional
pathogens

Reference:
1
Dasaraju, P. V. (n.d.). Infections of the respiratory system. Medical
Microbiology. 4th edition. Retrieved March 15, 2022, from
https://www.ncbi.nlm.nih.gov/books/NBK8142/

2
Ronald, A. R. (n.d.). Microbiology of the genitourinary system. Medical
Microbiology. 4th edition. Retrieved March 15, 2022, from
https://www.ncbi.nlm.nih.gov/books/NBK8136/#A5236

6. What tests may assist with the identification of the pathogen(s)?

● Antimicrobial susceptibility testing (AST) is used to determine which

antimicrobials will inhibit the growth of the bacteria or fungi causing a
specific infection. The results from this test will help a health care
practitioner determine which drugs are likely to be most effective in
treating a person’s infection.1
● Disk Diffusion test is a test that uses an agar plate on which an inoculum
of the organism is placed. After inoculation, several antimicrobial-laden
disks are placed on the plate, and evidence of bacterial growth is
observed after 18 to 24 hours.2
● Broth dilution test is a test whose method involves introducing a bacterial
inoculum into several tubes or wells filled with broth.3

Reference:
1
Testing.com. (2020, December 18). Antibiotic Susceptibility Testing. Retrieved
March 15, 2022, from https://www.testing.com/tests/antibiotic-susceptibility-
testing/#:%7E:text=What%20is%20being%20tested%3F,a%20culture%20of
%20the%20specimen.
2,3
Zeind, C. S., & Carvalho, M. G. (2018). Applied therapeutics: The clinical use
of Drugs. Wolters Kluwer Health.

7. Serratia marcescens grows from a culture of R.G. 's endotracheal

aspirate. How can it be determined whether an isolate represents a
true bacterial infection versus colonization or contamination?

A positive culture may represent colonization, contamination, or infection.

Infection is defined as the entrance and development of an infectious agent in
a human or animal body, whether or not it develops into a disease, and is
accompanied with signs and symptoms. Colonization is the presence of a
microorganism on/in a host, with growth and multiplication of the organism,
but without interaction between host and organism (no clinical expression, no
immune response). It does not make the host or patient sick and displays no
signs or symptoms. While, contamination is the presence of a microorganism
on a body surface or an inanimate object.

Nevertheless, the patient displayed respiratory symptoms of copious

amounts of yellow secretions with a chest radiograph of bilateral lower lobe
infiltrates making treatment against the pathogen necessary.

Reference:
Louisiana Office of Public Health (2017). Infection vs. colonization. Retrieved
from https://ldh.la.gov/assets/oph/Center-PHCH/Center-CH/infectious-epi/
HAI/MDRO2017/handouts/ColonizationvInfection.pdf

8. In light of the positive culture for Serratia, his increased respiratory

secretions, and a worsening chest radiograph, ventilator-associated
pneumonia (VAP) is likely. Pending susceptibility results, R.G. is
empirically started on imipenem and gentamicin. In review of his
patient records, R.G. has no known allergies. Are there equally
effective, less toxic options for this patient?

Despite the fact that the patient has no known allergies, neither imipenem
nor gentamicin are ideal options. Seizures have been linked to imipenem,
particularly in patients with renal failure and at doses greater than 50
mg/kg/day. Imipenem should be avoided because of its propensity to cause
seizures. 1 Given the patient's acute onset of renal failure and history of
seizures, other carbapenems, such as meropenem or doripenem, or alternative
antibacterial classes would be preferable.

Gentamicin may also be ineffective in this patient. His advanced age and
deteriorating renal function make him vulnerable to aminoglycoside
nephrotoxicity and ototoxicity (cochlear and vestibular). Advanced age has long
been held to be an important risk factor in the development of aminoglycoside-
related toxicity. For this reason many physicians avoid use of aminoglycosides
in the elderly. 2 In the absence of susceptibility results, a reasonable
recommendation would be to discontinue imipenem and gentamicin and treat
with meropenem or doripenem with or without a fluoroquinolone.
 Meropenem, a member of the carbapenem class, is widely used as
empirical therapy in the treatment of sepsis and septic shock regarding its
broad-spectrum activity and a low toxicity profile. 3 On the other hand,
Doripenem, a parenteral, broad-spectrum antibacterial agent of the
carbapenem family, is indicated as empirical therapy in serious bacterial
infections in adults. 4

Concomitant disease states should also be taken into account when deciding on
a treatment plan. For concomitant disease states:
● Diabetic or kidney transplant patients with candidemia may be better
treated with fluconazole or an echinocandin rather than nephrotoxic
amphotericin B products.
● Patients with a pre-existing seizure history should not receive imipenem if
less toxic therapy can be used.

Reference:
1
John, Bennett, E. M. D. (2020). Principles and Practice of Infectious Diseases
Ertapenem, Imipenem, Meropenem, Doripenem, and Aztreonam. ScienceDirect.
Retrieved March 15, 2022, from
https://www.sciencedirect.com/topics/medicine-and-dentistry/imipenem
2
Paterson, D. L., Robson, J. M., & Wagener, M. M. (n.d.). Risk factors for
toxicity in elderly patients given aminoglycosides once daily. Journal of general
internal medicine. Retrieved March 15, 2022, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1497032/
3
Lertwattanachai, T., Montakantikul, P., Tangsujaritvijit, V., Sanguanwit, P.,
Sueajai, J., Auparakkitanon, S., & Dilokpattanamongkol, P. (2020, April 15).
Clinical outcomes of empirical high-dose meropenem in critically ill patients
with sepsis and septic shock: A randomized controlled trial - journal of
intensive care. BioMed Central. Retrieved March 15, 2022, from
https://jintensivecare.biomedcentral.com/articles/10.1186/s40560-020-00442-
7#:~:text=Meropenem%2C%20a%20member%20of%20the,to%20other
%20beta%2Dlactam%20antibiotics.
4
Keam, S. J. (n.d.). Doripenem. Drugs, 68(14), 2021–2057.
https://doi.org/10.2165/00003495-200868140-00007
9. What factors should be included in calculating the cost of R.G.’s
antimicrobial therapy?
● Diagnostic measures: Physical examination (Auscultation), Chest
radiography, Laboratory chemistry, Urinalysis
● Drug therapy: All medications indicated for the treatment of the disease
● Duration of hospital admission
● Professional fees for healthcare providers
● Others: Inefficacy of antimicrobial therapy and its corresponding toxic
response, Other aids for therapeutic measures

Reference:
Ott, S. R., Hauptmeier, B. M., & Ernen, C. (n.d). Treatment failure in
pneumonia: impact of antibiotic treatment and cost analysis. Retrieved from
https://erj.ersjournals.com/content/erj/39/3/611.full.pdf

10. The Serratia was determined to be susceptible to ciprofloxacin. Oral

ciprofloxacin was considered for the treatment of R.G.’s presumed
Serratia pneumonia, but the IV route was prescribed. Why is the oral
administration of ciprofloxacin reasonable (or unreasonable) in R.G.?

The main reasons why IV therapy is favored in the beginning of the

treatment of seriously ill infectious patients are the short time of achieving
maximum serum concentrations (Tmax) and the 100% bioavailability.
Orally administered antibiotics must undergo absorption from the gut and
first pass metabolism before entering the systemic circulation, often causing a
bioavailability of less than 100%, resulting in delayed and lower maximum
concentrations in blood and at the site of infection compared to IV
administration.
The patient is clinically septic with a possible Serratia pneumonia.
Considering his unstable state, the bioavailability of oral ciprofloxacin cannot be
guaranteed; thus, he should be treated with IV antimicrobials.

Reference:
Broek, D. A. V. K. (2021, March 20). Systematic review: the bioavailability of
orally administered antibiotics during the initial phase of a systemic infection in
non-ICU patients - BMC Infectious Diseases. BioMed Central. Retrieved March
15, 2022, from
https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-05919-
w#citeas

11. What dose of IV ciprofloxacin should be given to R.G.? What factors

must be taken into account in determining a proper antimicrobial dose?

The dose that should be given for patient R.G. in the administration of
Ciprofloxacin IV is 300mg - 600mg.

The determination of dosage for any particular patient must take into
consideration the severity and nature of the infection, the susceptibility
of the causative organism, the integrity of the patient's host-defense
mechanisms, and the status of renal and hepatic function.

Dosage Guidelines for Ciprofloxacin IV

Location of Type of Unit Dose Daily Total Daily

infection Severity Frequency Dose

Urinary Tract Severe/ 200 mg Every 12 h 400 mg

Complicate
d

Lower Moderate 200 mg Every 12 h 400 mg

Respiratory
Tract (Gram- Severe/ 300 mg Every 12 h 600 mg
Negative) Complicate
d
Skin or skin
structure

Blood

Bone or Joint

Inhalation 400 mg Every 12 h 800 mg

Anthrax
(Post-exposure)
The duration of treatment depends upon the severity of infection. Generally,
ciprofloxacin should be continued for at least two days after the signs and
symptoms of infection have disappeared. The usual duration is 7 to 14 days
(parenteral therapy should be changed to oral ciprofloxacin tablets as soon as
the condition warrants). In general, intravenous ciprofloxacin should not
normally be given for greater than 14 days.

New Zealand Data Sheet (2019). Aspen Ciprofloxacin Injections. Retrieved from
https://www.medsafe.govt.nz/profs/Datasheet/a/aspenciprofloxacininj.pdf

12. R.G. 's respiratory status remains unchanged; thus, the ciprofloxacin
is discontinued and cefotaxime and gentamicin are started empirically. The
use of a constant IV infusion of cefotaxime is being considered in R.G.
In addition, the use of single daily dosing of gentamicin is being
discussed. What is the rationale for these approaches, and would either
be advantageous for R.G.?

β-Lactams, such as cefotaxime, are not associated with increased

bacterial killing with increasing drug concentrations. Pharmacodynamic activity
with β-lactams best correlates with the duration of time that antimicrobial
levels are maintained above the MIC, or minimum inhibitory concentration. The
animal model suggests that β-lactam antimicrobials should be dosed such that
their serum levels exceed the MIC of the pathogen as long as possible. This
observation appears to be most important in the neutropenic model, in which
the use of a constant infusion more reliably inhibits bacterial growth compared
with traditional intermittent dosing.
Considering the severity of R.G.’s infection and his elevated serum
creatinine level, he is not a candidate for single daily dosing of
aminoglycosides (i.e., 5–6 mg/kg every 24 hours). Independent of the
aminoglycoside-associated post-antibiotic effect (PAE), his current renal
function requires a reduced gentamicin dose to treat his infection. Reduced
dose with frequent administration. (1.7 mg/kg Q8H)
https://www.google.com/url?sa=t&source=web&rct=j&url=https://
med.stanford.edu/content/dam/sm/bugsanddrugs/documents/antimicrobial-
dosing-protocols/SHC-Aminoglycoside-Dosing-Guide.pdf&ved=2ahUKEwjv-
ai0xMv2AhWTQN4KHduBC4EQFnoECB0QAQ&usg=AOvVaw3887-GTTECL-t0-
yAp5u9l
Reference:
Czock, David; Markert, Christoph; Hartman, Bertram; Keller, Frieder (2009).
Pharmacokinetics and pharmacodynamics of antimicrobial drugs. Expert
Opinion on Drug Metabolism & Toxicology, 5(5), 475–487.
doi:10.1517/17425250902913808

13. Ceftriaxone (Rocephin), rather than cefotaxime (Claforan), is being

considered for the treatment of R.G. 's infection. Ceftriaxone is more
highly protein bound than cefotaxime. Why is protein binding important
in the selection of therapy?

Protein binding can involve plasma proteins, extracellular tissue proteins,

or intracellular tissue proteins. Many drugs in circulation are bound to plasma
proteins, and because bound drugs are too large to pass through biological
membranes, only free drugs are available for delivery to the tissues and to
produce the desired pharmacological action. Therefore the degree of protein
binding can greatly affect the pharmacokinetics of drugs.

Protein binding is most clinically significant for antimicrobial therapy,

where a high degree of protein binding serves as a drug “depot,” allowing for
increased duration of the time the drug concentration remains above the
bacterial minimum inhibitory concentration, adding to antimicrobial efficacy.

Ceftriaxone and Cefotaxime are similar in antibacterial spectrum and resistance

to beta-lactamases, but differ markedly in serum protein binding and
elimination half-life since Ceftriaxone is more highly protein bound.

Reference:
Davis, J. L. (2018). Pharmacologic principles of drug protein binding. Retrieved
from https://www.sciencedirect.com/topics/pharmacology-toxicology-and-
pharmaceutical-science/protein-binding

14. Despite “appropriate” treatment, R.G. is unresponsive to

antimicrobial therapy. What antibiotic specific factors may contribute
to “antimicrobial failure”?
 Antimicrobial resistance, in which antimicrobial medicines become
ineffective and infections become increasingly difficult or impossible to treat.
Antibiotics are becoming increasingly ineffective as drug-resistance spreads
globally leading to more difficult to treat infections and death. New
antibacterials are urgently needed – for example, to treat carbapenem-resistant
gram-negative bacterial infections as identified in the WHO priority pathogen
list. However, if people do not change the way antibiotics are used now, these
new antibiotics will suffer the same fate as the current ones and become
ineffective.

Reference:
World Health Organization. (2021, November 17). Antimicrobial resistance.
Retrieved March 15, 2022, from
https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance

15. What pharmacologic or pharmaceutic factors may be implicated in

failure of therapy?

 Subtherapeutic dosing regimens are common, particularly for

agents with a low therapeutic index, such as aminoglycosides. For
example, if the achievable peak gentamicin serum levels are only 3 to 4
mcg/mL, a serious gram-negative pneumonia may not respond to
aminoglycoside therapy. Given that only 20% to 30% of the
aminoglycoside penetrates from serum into bronchial secretions, only
0.5 to 1.0 mcg/mL may exist at the site of infection, a level that may
be insufficient to treat pneumonia.
 loading doses. In patients with renal failure, aminoglycosides or
vancomycin should be started with a loading dose. If the clinician fails
to use a loading dose, it may take several days to reach a therapeutic
level.
 , reduced oral absorption due to drug interactions (e.g.,
concomitant oral ciprofloxacin with antacids or iron) is another cause of
subtherapeutic antimicrobial levels and potential drug failure.
 Another potential reason for antimicrobial failure is inadequate
therapy duration. A delay in adequate antibiotic therapy may lead to
progressive deterioration and the development of complications. 4
Reference:
3
Levison, M. E., & Levison, J. H. (n.d.). Pharmacokinetics and
pharmacodynamics of antibacterial agents. Infectious disease clinics of North
America. Retrieved March 15, 2022, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675903/

16. What host factors may contribute to the failure of antimicrobial

therapy?

Infection of prosthetic material, like the catheter pertaining to the

case of patient R. G. could be one factor. The main risk of using a catheter is
that it can sometimes allow bacteria to enter the body. This can cause an
infection in the urethra, bladder or, less commonly, in the kidneys. Thus, when
this happens, an increased isolation of resistant organisms with the
antimicrobial therapy occurs. So, it is recommended that the catheter be
removed and a new catheter inserted, with specimen collection from the freshly
placed catheter, before antimicrobial therapy is initiated for symptomatic
infection.

Reference:
Nicolle, L. E. (2014). Catheter associated urinary tract infections. Antimicrobial
Resistance and Infection Control, 3(23).
https://aricjournal.biomedcentral.com/articles/10.1186/2047-2994-3-23#

17. Other than initiation of adequate antimicrobial therapy, what

adjunct measures can be considered in this patient with septic shock?

● It recommends empiric broad-spectrum therapy with one or more

antimicrobials for patients presenting with sepsis or septic shock to cover
all likely pathogens (including bacterial and potentially fungal or viral
coverage
● It recommends optimizing dosing strategies of antimicrobials based on
accepted pharmacokinetic/pharmacodynamic (PK/PD) principles and
specific drug properties.
● It recommends rapidly identifying or excluding a specific anatomical
diagnosis of infection that requires emergent source control and
implementing any required source control intervention as soon as
medically and logistically practical.
● It recommends prompt removal of intravascular access devices that are a
possible source of sepsis or septic shock after other vascular access has
been established.
 ● It recommends the use of norepinephrine as the first-line agent over
other vasopressors. - used to treat life-threatening low blood pressure
(hypotension) that can occur with certain medical conditions or surgical
procedures.
● It recommends that the principles of palliative care (which may include
palliative care consultation based on clinician judgment) be integrated
into the treatment plan, when appropriate, to address patient and family
symptoms and suffering.

Reference:
Laura,E., Andrew, R., & Waleed, A. (2021). Surviving sepsis campaign:
international guidelines for the management of sepsis and septic shock 2021.
Critical Care Medicine, 49(11), e1063-e1143.
https://journals.lww.com/ccmjournal/fulltext/2021/11000/surviving_sepsis_ca
mpaign__international.21.aspx

DRUGS IN THE CASE

1. HYDROCORTISONE- corticosteroids
- Hydrocortisone is a steroid (corticosteroid) medicine. It works by
calming down your body’s immune response to reduce pain, itching
and swelling (inflammation).
- Few studies exist regarding dosing protocols for corticosteroids in
GCA. It is generally agreed that most patients with suspected GCA
should be started on oral prednisone 40-60 mg/day, with a
temporal artery biopsy performed within 1 week. [95] Prednisone
doses of 80-100 mg/day have been suggested for patients with
visual or neurologic symptoms of GCA. [142] Follow-up care within
72 hours after starting therapy should be arranged.
2. PHENYTOIN
- Phenytoin is an anti-convulsant drug which works by blockade of
voltage-dependent membrane sodium channels responsible for
increasing the action potential. Through this action, it obstructs the
positive feedback that sustains high-frequency repetitive firing, thus
preventing the spread of the seizure focal point.
- Adverse effects potentially include the following:

 Rash
 Sedation
 Peripheral neuropathy[6]
  Phenytoin encephalopathy[7]
 Psychosis
 Locomotor dysfunction
 Hyperkinesia
 Megaloblastic anemia
 Decreased bone mineral content
 Stevens-Johnson syndrome
 Toxic epidermal necrolysis
 Immunoglobulin A deficiency
 Gingival hyperplasia
 Dress syndrome (drug reaction accompanied by eosinophilia and
systemic symptoms)
 Cardiovascular collapse
 Hypotension
 Arrhythmias
 Hydantoin syndrome in newborns
 Purple glove syndrome[8
Gupta M, Tripp J. Phenytoin. [Updated 2021 Jul 25]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2022
Jan-.https://www.ncbi.nlm.nih.gov/books/NBK551520/

3. IMIPENEM
- CARBAPENEMS ( BETA LACTAM DRUGS)
- Imipenem inhibits bacterial cell-wall synthesis by binding to
penicillin-binding proteins; cilastatin prevents renal metabolism of
imipenem
- Initiated due to ventilator-associated pneumonia (VAP)
- Ventilator-associated pneumonia is a lung infection that
develops in a person who is on a ventilator. A ventilator is a
machine that is used to help a patient breathe by giving oxygen
through a tube placed in a patient’s mouth or nose, or through a
hole in the front of the neck.
- Susceptible organisms
- Acinetobacter spp, Alcaligenes xylosoxidans, Bacteroides spp,
Citrobacter spp, Clostridium spp, Enterobacter spp, Escherichia coli,
Gardnerella vaginalis, Haemophilus influenzae, Haemophilus
parainfluenzae, Klebsiella spp, Morganella morganii, Nocardia spp,
Propionibacterium spp, Proteus vulgaris, Providencia rettgeri,
Pseudomonas aeruginosa, Rhodococcus equi, Serratia
marcescens, Staphylococcus aureus (penicillinase-producing),
 Staphylococcus epidermidis, enterococci, group B/D streptococci,
Streptococcus pyogenes, Streptococcus pneumoniae

- Adverse Effects
o 1-10%
o Phlebitis (2-5%)
o Eosinophilia (4%)
o Miscellaneous dermatologic effects (<3%)
o Potentially false-positive Coombs test (2%)
o Miscellaneous hematologic effects (<2%)
o Transient increase in blood urea nitrogen (BUN) or serum
creatinine (<2%)
o Seizures (1.5%)
o Nausea, diarrhea, vomiting (1-2%)

o <1%
o Abnormal urinalysis
o Agitation
o Anaphylaxis
o Anemia
o Confusion (acute)
o Dizziness
o Dyskinesia
o Emergence of resistant strains of Pseudomonas aeruginosa
o Fever
o Hypersensitivity
o Hypotension
o Elevated liver function test (LFT) results
o Increased prothrombin time (PT)
o Neutropenia (including agranulocytosis)
o Palpitations
o Pruritus
o Pseudomembranous colitis

https://reference.medscape.com/drug/doribax-doripenem-342563#10

4. GENTAMICIN
- Initiated due to ventilator-associated pneumonia (VAP) due to
SERACIA MARESECENS
- Gentamicin is an aminoglycoside antibiotic. It exhibits bactericidal
activity against aerobic gram-negative bacteria makes gentamicin a
good option to treat several common infections. Since gentamicin
has a minimal gastrointestinal absorption, its administration is
usually by parenteral routes.
- The most common microorganisms in clinic settings that present
appropriate therapeutic response are members of the
Enterobacteriaceae family (e.g., Escherichia coli, Klebsiella
pneumoniae, Serratia spp. And Enterobacter spp.), Pseudomonas
aeruginosa, and some strains of Neisseria, Moraxella, and
Haemophilus genera.
- The combination with another antibiotic, especially beta-lactams, is
reasonable in bacterial endocarditis, enterococcal bacteremia, and
other severe infections, although other antibiotics are preferable in
these settings.[5] The beta-lactams break the bacterial cell wall and
allow gentamicin to get in the bacterial cytoplasm where it can
access the ribosomal target, explaining why this combination can be
useful against gram-positive bacterial infection.
- Gentamicin passes through the gram-negative membrane in an
Oxygen-dependent active transport. As oxygen is required, this is
why aminoglycosides are not effective in anaerobic bacteria.
- The dose of 5 to 7mg/kg daily given intravenously (infused over 30
to 120 minutes) is the preferable way for gentamicin application in
most systemic infections by sensible germs, even though the
traditional dosing of 3 to 5 mg/kg/day divided into doses every 8
hours is still an option in certain scenarios.
- The postantibiotic effect (PAE), another feature of aminoglycosides,
is the characteristic for bacterial regrowth suppression that persists
a few hours after antibiotic concentration falls below the minimum
inhibitory concentration (MIC); high peak concentration also
advantages the PAE.[10] Therefore, these properties explain the
reason for gentamicin is preferable in high-dose regimens
associated with extended-interval doses.
- Adverse Effects
- Characteristically, gentamicin reaches high concentrations in the
renal cortex and the inner ear. The latter may be injured, leading to
auditory and, especially, vestibular dysfunction. The first
manifestation of cochlear damage is often high-pitched tinnitus,
which may last a few weeks after the gentamicin is interrupted.
- High risk for aminoglycoside toxicity (e.g., older age
https://www.ncbi.nlm.nih.gov/books/NBK557550/

5. CIPROFLOXACIN
- Serratia pneumonia, because it is susceptible to ciprofloxacin.
- Ciprofloxacin is an antibiotic. It belongs to a group of antibiotics
called fluoroquinolones
- The most common side effects of ciprofloxacin tablets and liquid are
feeling sick (nausea) and diarrhoea.
- Avoid taking the tablets or liquid together with dairy products like
milk, cheese and yoghurt.
- It is rare, but the tablets and liquid can cause weak muscles, pain
or tingling in your legs and arms, painful or swollen joints and
tendons, and a fast or irregular heartbeat.
https://www.nhs.uk/medicines/ciprofloxacin/

6. CEFOTAXIME
- Used in place of CIPROFLOXACIN in treatment of seratia marescens
causing pneumonia
- Cefotaxime (CTX) is a beta-lactam antibiotic classified as a third-
generation cephalosporin, which was first synthesized in 1976 and
is FDA approved to treat gram-positive, gram-negative, and
anaerobic bacteria.[1] Its broad-spectrum antibacterial activity is
useful in treating the susceptible strains of bacteria affecting the
lower respiratory tract, genito-urinary tract, central nervous
system, intra-abdominal infections, bone and joint infections, skin
infections, gynecologic infections, and septicemia.[2] Cefotaxime
may also be used prophylactically prior to surgery to prevent
surgical infections.
- Cefotaxime(CTX) exerts its mechanism of action by binding
penicillin-binding proteins (PBPs) via beta-lactam rings and
inhibiting the definitive activity of transpeptidation in peptidoglycan
cell wall synthesis of susceptible bacterial organisms.[8][9] The
inability to form a bacterial cell wall further causes the autolysis of
the bacteria.
- Susceptible organisms include:
-
- Gram-positive bacteria
-
 Enterococcus spp
 Staphylococcus aureus
 Staphylococcus epidermidis
 Streptococcus pneumoniae
 Streptococcus pyogenes
 Streptococcus viridans spp

 Anaerobic bacteria

 Bacteroides spp.
 Clostridium spp
 Fusobacterium spp
 Peptococcus spp
 Peptostreptococcus spp

 Gram-negative bacteria

 Acinetobacter spp.
 Citrobacter spp
 Enterobacter spp
 Escherichia coli
 Haemophilus influenzae
 Haemophilus parainfluenzae
 Klebsiella spp.
 Morganella morganii
 Neisseria gonorrhoeae
 Neisseria meningitidis
 Proteus mirabilis
 Proteus vulgaris
 Providencia rettgeri
 Providencia stuartii
 Serratia marcescens

Adverse Effects
Local reaction: pain, swelling (most common)
Hypersensitivity: rash, pruritis, anaphylaxis
Gastrointestinal effects: nausea, vomiting, diarrhea
Pseudomembranous Colitis
Headache
Elevation in liver enzymes
Elevation in BUN and creatinine
Hematologic: Neutropenia, leukopenia, agranulocytosis
Monitoring
Cefotaxime administration and dosing require adjusting in geriatric populations,
patients with decreased renal function, and hepatic dysfunction. Renal function and
liver enzymes require routine monitoring. The half-life of cefotaxime is generally one
hour, and severe kidney dysfunction may prolong the half-life of cefotaxime and its
metabolite desacetylcefotaxime.[9] CBC should also be monitored with cefotaxime
use as there are reports of hematologic changes such as neutropenia, leukopenia, and
agranulocytosis. Cefotaxime, like other cephalosporins, may also cause a false
positive direct coombs test.
Padda IS, Nagalli S. Cefotaxime. [Updated 2021 Nov 25]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
https://www.ncbi.nlm.nih.gov/books/NBK560653/

7. CEFTRIAXONE
- Ceftriaxone, an FDA-approved third-generation cephalosporin
antibiotic
Serratia infections

Serratia marcescens, a motile, gram negative bacillus, which has been

classified as a member of the family, Enterobacteriaceae, is widespread in the
environment, but it is a rare cause of human disease. The Serratia species are
occasionally recognized as a cause of hospital acquired infections such as
urinary tract infections, respiratory tract infections and wound infections.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592283/#!po=32.8125

Should be treated with an aminoglycoside plus an antipseudomonal beta-

lactam, as the single use of a beta-lactam can select for resistant strains. Most
strains are susceptible to amikacin, but reports indicate increasing resistance to
gentamicin and tobramycin.

An important characteristic of Serratia marcescens is its ability to produce a

beta lactamase which confers resistance to the broad spectrum, beta
lactum antibiotics, which often complicates the therapy.
https://emedicine.medscape.com/article/228495-medication#:~:text=Serratia
%20infections%20should%20be%20treated,resistance%20to%20gentamicin
%20and%20tobramycin.

What is meant by Gram negative?

Gram-negative: Gram-negative bacteria lose the crystal violet stain (and take
the color of the red counterstain) in Gram’s method of staining. This is
characteristic of bacteria that have a cell wall composed of a thin layer of a
particular substance (called peptidoglycan)

Gram-positive bacteria cause tremendous problems and are the focus of many
eradication efforts, but meanwhile, Gram-negative bacteria have been
developing dangerous resistance and are therefore classified by the CDC as a
more serious threat. Their outer membranes are hidden by a slime layer that
hides the antigens present in the cell.

Sepsis

Sepsis—A life-threatening condition caused by a dysregulated host response to

infection, resulting in organ dysfunction.
Septic shock — a severe condition that occurs when the body’s blood pressure
falls and organs shut down

The beta-lactamases enzymes inactivate beta-lactam antibiotics by

hydrolyzing the peptide bond of the characteristic four-membered beta-lactam
ring rendering the antibiotic ineffective.