An approach to antibiotic therapy: A primer for all specialties

G. Dominic Rodriguez

Senior Consultant Physician, Department of Medicine, Kauvery Hospital, Tennur

Editor’s Note: This paper has been adapted from a lecture given by the author at a clinical meeting

Background

Judicious use of antibiotics and appropriate early initiation for the right patient

The factors that determine the patients in Casualty as sick

  • NEWS2 (National Early Warning Score)
  • RR
  • SpO2
  • BP
  • Pulse
  • Conscious level
  • Temperature
  • qSOFA (Quick Sequential Organ Failure Assessment)

Example,

GCS – < 15,                 1 point

BP – < 100 systolic,    1 point

RR – > 22 bpm,           1 point

  • 0 – 1 point- not high risk
  • 2 or 3 – high risk
  • SpO2 + qSOFA even more valuable in the emergency room or OPD

Acute Fevers

  • Acute fevers can be undifferentiated [fever >38.3°C (101.0°F) for >2 days and lasting up to 14 days] or can have some localizing signs.
  • Focused history and examination most valuable
  • If you have a patient in sepsis and plan iv antibiotics do not start antibiotics without obtaining an appropriate specimen for culture.
  • Look for any localising clues
  • In all complicated UTIs obtain urine for culture before starting antibiotics.

Sepsis guidelines recommend antibiotic therapy to be initiated within 1 hr of presentation

Whenever a Bacterial Infection is suspected and Antibiotic is planned

  1. What is the likely site of infection?
  2. Is it likely to be a Gram-positive or Gram-negative infection or a mixed infection?
  3. What tests should I send?
  • Blood culture
  • Urine culture
  • Sputum culture – grams stain, special stains
  • Tissue culture or pus culture- swabs are generally useless
  • LP – CSF analysis (stains and panels)
  1. What preliminary reports can I get and – how can I utilize the information?

Correct Blood culture Practices

  • Collect 2 sets of blood cultures before starting an antibiotic.
  • A set means aerobic and anaerobic collection in 2 bottles from 2 different sites.
  • Alcohol chlorhexidine – STERILIUM – should be used for disinfection.
  • The manufacturer specifies bottle volume
  • When catheter related infection (CLABSI) is suspected a sample is obtained simultaneously from the IV catheter and the periphery
  • 3 sets of blood cultures are obtained at 3 different sites at least 1 hr apart when IE is suspected.
  • Blood is best collected when patient has chills or feels cold rather than after high-grade fever.

Sputum

An acceptable specimen

  • 25 leucocytes
  • < 10 epithelial cells/ low power field
  • Sputum Grams stain / AFB stain / fungal KOH mounts requested
  • Sputum culture / genexpert TB RIF / galactomannan are other tests

SSTI (Skin and Soft Tissue Infection)

In SSTI Tissue obtained by debridement is better than surface swabs

Urine Culture

  • Midstream specimen in wide-mouthed clean catch specimen
  • Never collect urine from old indwelling catheter.
  • If CAUTI (Catheter-Associated Urinary Tract Infection) is suspected remove the old catheter, insert a new one and collect specimen.
  • Suprapubic aspirate is another option
  • Always send urine routine along with the sample

Empiric antibiotic regimens

1. Community-acquired intra-abdominal infections in adults

Likely organisms – Gram negatives and anaerobes

Treatment: Piperacillin-tazobactam – 4.5 g IV every 6 hr or a combination regimen with metronidazole

2. Necrotizing fasciitis

Likely organisms – mixed facultative aerobic gram positive, gram negative and anaerobes

Treatment: Meropenem + vancomycin + dalacin

3. Severe community acquired pneumonia

Likely organisms – Gram-positive, atypical or viral

Treatment: Cefoperazone sulbactum + macrolide + oseltamivir

4. VAP –Ventilator-Associated Pneumonia

Likely organisms – Pseudomonas, Klebsiella, Acinetobacter- SPACE bugs plus MRSA

Treatment: 2 agents against MDR GNB plus MRSA cover is recommended

Eg. Zavicefta + Aztreonam and teicoplanin or vancomycin

Meropenem + moxifloxacin and tigecycline

Adjunct nebulized antibiotics like colistin

Ampicillin + sulbactam.

5. CRBSI – Catheter-Related Bloodstream Infections.

Likely Organism – CONS (coagulase-negative staphylococci), S. Aureus, MRSA, Candida

Treatment: Vancomycin, teicoplanin, linezolid, daptomycin. + Gram-negative bacteria MDR

cover recommended.

Plus echinocandin if candidemia is suspected

Removal of the line after taking cultures – Essential

6. UTI

Likely organisms – coliforms, enterococci

Treatment: Meropenem + (ampicillin or Piptaz)

To cover ESBL , enterococci, Staph

CBD Removal when possible

7. Meningitis – Medical Emergency

Antibiotic Time – Out

  • Escalate
  • De escalate
  • Stop
  • Change

Interpretation of culture reports

Clinical Data 1

DiagnosisLeft ASOM
SpecimenEar Swab

Test Report

Gram stain: Few pus cells and gram-positive cocci

Organism isolated Staphylococcus aureus (MSSA) –Small numbers

Antibiotic Susceptibility Test – Kirby Bauer Disk Diffusion Method.

AntimicrobialInterpretationAntimicrobialInterpretationAntimicrobialInterpretation
OxacillinSVancomycinSLevofloxacinR
CefoxitinSLinezolidSErythromycinS
CefazolinSGentamicinSClindamycinS
CefuroximeSCiprofloxacinRCo-TrimoxazoleS
CeftriaxoneSTigecyclineSDoxycyclineS

MSSA (Methicillin susceptible staphylococcus aureus)

2 drugs are used to check methicillin susceptibility –Oxacillin and cefoxitin

If both are sensitive –Reported as MSSA

Drug of Choice

Oxacillin/CefazolinVancomycin/linezolid
CNS infections (meningitis, brain abscess, subdural abscess) – cefazolin will not be effective.

  • Slow bactericidal activity

  • MIC creep

  • It kills staphylococci more slowly

  • Clearly inferior to beta lactams for MSSA bacteremia and infective
  • endocarditis.

  • Tissue penetration is variable –limited penetration in bone, lung epithelial lining fluid and CSF.


Beware of linezolid side effects

Clinical Data 2

DiagnosisAbscess Chest
SpecimenPus
Report statusFinal

Test Report

Gram stain: Many pus cells and gram-positive cocci

Organism isolated: Staphylococcus aureus (MRSA) Heavy growth

Antibiotic Susceptibility Test: Kirby Bauer Disk Diffusion Method

AntimicrobialInterpretationAntimicrobialInterpretationAntimicrobialInterpretation
OxacillinRVancomycinSLevofloxacinS
CefoxitinRLinezolidSErythromycinS
CefazolinRGentamicinSClindamycinS
CefuroximeRCiprofloxacinSCo-TrimoxazoleS
CeftriaxoneRDaptomycinSDoxycyclineS
TigecyclineS

MRSA (Methicillin Resistant Staphylococcus Aureus)

Drug of Choice

  • Vancomycin
  • Linezolid
  • Daptomycin
  • Cotrimoxazole
  • Doxycycline/minocycline
  • Clindamycin
  • Gentamicin

SSTI (Skin and Soft Tissue Infections)

Uncomplicated – CA-MRSA (Community-Acquired)

  • Clindamycin Doxycycline/minocycline
  • Cotrimoxazole

Complicated SSI – DEEP seated/surgical /traumatic

  • IV vancomycin /linezolid + clindamycin
  • Clindamycin provides anaerobic cover, reduces Staph and endotoxin production.

Infective endocarditis

MRSAMSSA
Native valve
IV vancomycin/Daptomycin
Native valve
Cefazolin 2 g IV Q8h
Prosthetic valve

  • IV vancomycin or Daptomycin +gentamicin + Rifampicin 900 mg/day

  • Clindamycin and linezolid are not used for infective endocarditis/Endovascular infections.


Prosthetic valve
Cefazolin + gentamicin + rifampicin 300 – 900 mg/day

*Rifampicin- started after 5 days of primary antibiotic

Clinical Data 3

Tissue sample sent from a diabetic foot infection

Clinical Data 4

Uncontrolled Diabetes With fever and Dysuria

Uncomplicated UTI

  • Nitrofurantoin
  • Cotrimoxazole
  • Ampi or amoxicillin
  • Cefixime

Clinical Data 5

ESBL (Enterobacteriales)

Identified by resistance to 3rd gen Cephalosporins and that will respond only to Penems and rarely to Piptaz if MIC < 4

Extended spectrum Beta lactamases

  • Escherichia coli
  • Klebsiella
  • Enterobacter
  • Citrobacter
  • Serratia
  • Proteus species including morganella/providencia

*Acinetobacter and pseudomonas do not come under this group

Gram Negative Bacteria

3rd gen sensitivity – Ceftriaxone, Ceftazidime

Clinical Data 6

Drug of choice

Piptaz MIC – 8

Clinical Data 7

Drug of Choice

AMP C beta lactamase producers resistant to BL + BLI (Beta-lactam-beta-lactamase inhibitor) also but sensitive to cefepime 4th gen.

If patient is critically ill – emphysematous pyelonephritis

  • Carbapenems (Meropenem/Imipenem) must be started in this group – ESBL and AMP – C

Complicated UTI but only cystitis and hemodynamically stable

  • Cotrimoxazole/Quinolone
  • Nitrofurantoin/Fosfomycin – not to be used for pyelonephritis

Clinical Data 8

Enterococcus in urine

Drug of Choice

  • Enterococcal UTI is the next common organism after enterobacteriales.
  • If sensitive to penicillin will respond well to a combination of ampi + ceftriaxone 2 g IV BD
  • Vanco, teicoplanin and linezolid are other choices in case of resistance
  • Daptomycin + linezolid is one of the practical choices for VRE

Clinical Data 9

CRE –Carbapenem Resistant Enterobacterales

CRE refers to organisms displaying resistance to either meropenem or imipenem or those Enterobacterales isolates producing carbapenemase enzymes

  • Most common – K. pneumoniae
  • KPC (Klebsiella pneumoniae carbapenemase)
  • OXA 48 like
  • NDM

Gram Negative Bacteria

3rd gen sensitivity – Ceftriaxone, Ceftazidime

Important Don’ts remember

Important Don’ts to remember
DaptomycinPneumonia
TigecyclineBacteremia or Pseudomonas
LinezolidMRSA bacteremia
CefepimeAnaerobes, EnterococcI
ErtapenemAcinetobacter, Pseudomonas, Enterococci - “APE”
AztreonamGram positives
Aminoglycoside monotherapyNon-UTI indication
RifampinMonotherapy
MicafunginUTI or meningitis
FluconazoleCandida krusei

Learning Points

  • Basic knowledge of sites of infections, probable organism responsible, gram positive, negative or mixed infection likelihood is necessary for good practice
  • Identify sick patients early and after essential tests start appropriate empirical antibiotic therapy.
  • Take antibiotic time out in 3 days interpret culture reports and revise, refine treatment.
  • Discuss with microbiologist and gain more information
  • Get surgical help to drain any collections
  • Use antibiotics at appropriate dosages for the correct duration
  • Use antibiotics from companies of good standards.
  • Correct therapy may yet go to waste if, the drug is of poor quality
  • Utilize antibiotic synergy whenever possible.

Conclusion

Preventing these serious infections and its spread is most important and simple discipline and stewardship can achieve it

Acknowledgment

Sincere thanks to Dr. Thilagavathy MD – Lab Director Kauvery Hospital for valuable inputs

References

  • Rieg S, Joost I, Weiß V, et al. Combination antimicrobial therapy in patients with Staphylococcus aureus bacteraemia-a post hoc analysis in 964 prospectively evaluated patients. Clin Microbiol Infect. 2017;23(6):406.e1-406.e8.
  • Khilnani GC, Zirpe K, Hadda V, et al. Guidelines for Antibiotic Prescription in Intensive Care Unit. Indian J Crit Care Med. 2019;23(Suppl 1):S1-S63.
  • John Quale MD; carbapenem resistant E.Coli, K Pneumonie and other Enterobacterales CRE; April 19,2024.

Dr. G. Dominic Rodriguez - Top General Physician in Trichy Tennur

Dr. G. Dominic Rodriguez
Senior General Physician

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