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Rational use of

antibiotics in
pregnancy
Ricardo Manalastas, Jr., MD
UNILAB ICON (Interspecialty Conference ) 2014

Outline
Introduction
Physiologic Changes in Pregnancy
Pharmacokinetic Consequences
Principles of Antibiotic Pharmacotherapy
Illustrative Cases
Clinical Evaluation of Febrile Patient
to Determine probable Pathogen &
Empiric Antibiotics

Introduction
Antibiotic Stewardship
Rational use
Clearly indicated
Prophylaxis e.g., CS,
hysterectomy, episiotomy
(2nd degree)
Therapy e.g., established
infections like IAI, puerperal
sepsis
Ricardo Manalastas, Jr., MD

Introduction
Antibiotic Stewardship
Benefits outweigh risks
Adverse effects
Maternal
Fetal
FDA classification of drugs
for Pregnancy and Lactation
Ricardo Manalastas, Jr., MD

Introduction
Antibiotic Stewardship
Appropriate choice
Local drug susceptibility of
likely pathogens; e.g., ESBL
Correct dosage, route and
duration

Ricardo Manalastas, Jr., MD

Physiologic Changes in
Pregnancy
Expanded plasma volume
Increased glomerular filtration rate
More active liver enzymes
GI alterations
Nausea & vomiting
Decreased gastric emptying and
intestinal transit time
Increased fetal compartment

Ricardo Manalastas, Jr., MD

Pharmacokinetic
Consequences
Lower plasma levels of
drugs(antibiotics) in pregnancy
By 20-50%
Most marked in 3rd trimester
and immediately post-partum

Ricardo Manalastas, Jr., MD

Pharmacokinetic
Consequences
Lower plasma levels of
drugs(antibiotics) in pregnancy
Involves beta lactams,
fluoroquinolones and
aminoglycosides

Ricardo Manalastas, Jr., MD

Pharmacological
Consequences
Lower plasma levels of
drugs(antibiotics) in pregnancy
Dose adjustments
Ideally, measure serum levels
Practically, use the higher
recommended dosage range
e.g., gentamicin 3-5 mg/kg;
use 5 mg/kg
Ricardo Manalastas, Jr., MD

Pharmacological
Consequences
Using the higher range of the
recommended antibiotic dose
Requires a change in the
common (mis)conception of
"using the least amount of drug
during pregnancy to avoid
adverse effects"

Ricardo Manalastas, Jr., MD

Pharmacological
Consequences
Using the higher range of the
recommended antibiotic dose
Avoids treatment failure of
infections due to subtherapeutic levels of (even the
correctly chosen) antibiotics.

Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Bactericidal preferred over
bacteriostatic for
Severe infections
Immunosuppressed host

Ricardo Manalastas, Jr., MD

Case: reactive RPR and


TPHA in a 14wk G1
Diagnosis?
Syphilis
Which of the ff?
1. Erythromycin
2. Penicillin
3. Doxycycline
4. Amoxicillin
Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
During combination antibiotic
therapy, administer the CIDAL
drug(s) ahead of the STATIC

Ricardo Manalastas, Jr., MD

Case: fever 2nd day post-CS for


PROM, with distended, tender
abdomen
Diagnosis?
Puerperal Sepsis
Which sequence is best?
1. Ampicillin Clindamycin
Gentamicin
2. Clindamycin Ampicillin
Gentamicin
3. Ampicillin Gentamicin
Clindamycin
Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Combination drugs, when
indicated, must exhibit
SYNERGISM
Different site of action
Cell wall for beta-lactams
Nucleus for aminoglycosides

Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Combination drugs, when indicated,
must exhibit SYNERGISM
Different mechanism of action
Cilastatin prevents renal
excretion of Imipenem
Clavulanate/tazobactam
prevent degradation of
amoxicillin/piperacillin

Ricardo Manalastas, Jr., MD

Case:
fever, chills & flanks pains with lethargy in 30wk
AOG G1
Diagnosis?
Acute Pyelonephritis, possible
urosepsis
Which of the ff is NOT appropriate ?
1. Imipenem-cilastatin
2. Ceftriaxone-piptazo
3. Ceftazidime-amikacin

Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Parenteral therapy is generally
preferred to oral, especially
in severe infections
in Immunocompromised host
when GI absorption is inferior
Step-down (from parenteral to
oral) therapy is dictated by clinical
conditions.
Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Step-down Therapy
Initiated 1-3 days after
improvement e.g., lysis of fever,
relief of pain
Continued close observation
during the 1st 1-2 days of oral
therapy
Recurrence of symptoms
Tolerance of oral drugs
Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Step-down Therapy
Assure compliance with total
duration of therapy e.g., 7 days
onwards
Advantage of antibiotics with
both parenteral and oral
preparations

Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Frequency of administration
depends on pharmaco-dynamics
TIME-DEPENDENT
the more frequent the
administration, the more
bacteria are killed
Divided dosing of total daily
dose
Beta-lactams
Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Frequency of administration
depends on pharmaco-dynamics
DOSE-DEPENDENT
the higher the dose given at
any one time, the more
bacteria are killed
Single bolus of the total daily
dose
Aminoglycosides
Ricardo Manalastas, Jr., MD

Case:

6 days post-stat CS, fever w purulent


wound discharge, erythema , tenderness and
swelling; no significant pelvic tenderness/mass

Diagnosis?
Surgical Site Infection
Which in-hospital treatment is most
appropriate?
1. Cefazolin 2 g IV q6h + gentamicin
80 mg IV q8h
2. Cefazolin 4 g IV q12 + gentamicin
240 mg IV bolus
3. Cefazolin 2g IVq6h + gentamicin
240 mg IV bolus
Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Degree of protein binding of drug
influences it's suitability for use in
maternal infections transmitted to
fetus in-utero

Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Reduction/elimination of microbial
load facilitates response to drug
therapy
Antisepsis
Chemical e.g., chlorhexidine
Mechanical e.g., cleansing,
irrigating
Surgical extirpation
Ricardo Manalastas, Jr., MD

Principles of Antibiotic
Pharmaco-therapy
Known polymicrobial infections
e.g., pelvic, should have empiric
broad spectrum drug coverage

Ricardo Manalastas, Jr., MD

Clinical Evaluation of Febrile Post-partum Patient:


to Determine Probable Offending Organism(s) and Guide Empiric
Antibiotic Therapy

Clinical Parameters
Onset of fever in relation to
procedure (temperature curve)
Status of the wound, if any
Abdominal findings
Internal examination findings

Ricardo Manalastas, Jr., MD

Clinical Scenario 1
ONSET OF FEVER
6-24 hours post surgery or delivery
TEMPERATURE
39 C Marked elevation
ABDOMINAL EXAMINATION
Benign
PELVIC EXAM
Minimal non-foul smelling discharge,
mild to moderate tenderness
ORGANISM
Gram (+) cocci
e.g. Group B streptococci
TREATMENT
Ampicillin or 1st gen cephalosporins
Ricardo Manalastas, Jr., MD

Clinical Scenario 2
ONSET OF FEVER
Approximately 48 hours after insult
TEMPERATURE
37.5-38.5 C Moderate elevation
ABDOMINAL EXAMINATION
Mild to moderate lower quadrant
tenderness
PELVIC EXAM
Mild to moderate discharge , non-foul
smelling, non-purulent, moderate to
severe tenderness
ORGANISM
Gram (-) rods, aerobic
e.g.: E. coli
TREATMENT
1st or 2nd gen cephalosporins
Ricardo Manalastas, Jr., MD

Clinical Scenario 3
ONSET OF FEVER
72-96 hours after insult
TEMPERATURE
37.5-38.5 C Moderate elevation
ABDOMINAL EXAMINATION
Wound with tenderness, erythema, edema
and induration
PELVIC EXAM
Mild to moderate discharge , non-foul
smelling, non-purulent, minimal
tenderness
ORGANISM
Variable in wound infection
TREATMENT
Drainage and debridement of wound with
use of antiseptics (chlorhexidine) +/antibiotics
Ricardo Manalastas, Jr., MD

Clinical Scenario 4
ONSET OF FEVER
72-96 hours after insult
TEMPERATURE
37.5-38.5 C Moderate elevation
ABDOMINAL EXAMINATION
Wound benign, marked lower quadrant
tenderness
PELVIC EXAM
Moderate discharge, possibly purulent, very
foul smelling, marked tenderness on
bimanual exam
ORGANISM
Gram (-) rods, anaerobic
e.g.: Bacteroides sp.
TREATMENT
Cefoxitin, Cefotetan, Clindamycin,
Metronidazole and other anaerobic
coverage drugs
Ricardo Manalastas, Jr., MD

Clinical Scenario 5
ONSET OF FEVER
7 days after insult
TEMPERATURE
37.5-38.5 C Moderate elevation
ABDOMINAL EXAMINATION
Wound benign, marked lower
quadrant tenderness
PELVIC EXAM
Moderate to heavy discharge, very
purulent, non-foul
smelling marked tenderness on
bimanual exam
ORGANISM
Chlamydia trachomatis
TREATMENT
Erythromycin or Doxycycline
Ricardo Manalastas, Jr., MD

Thank you!

Ricardo Manalastas, Jr., MD