Cracking EGGS with a HAMMER
Steven Lim
ID Physician
Hospital Raja Permaisuri Bainun
Cracking eggs with a hammer�
Meropenem
Ceftriaxone
Ciprofloxacin
etc…etc…
Highly susceptible bacteria
Antimicrobial Resistance (AMR)
Using broad spectrum antibiotics against highly susceptible bacteria�
Case Vignette
47 yo gentleman
Alleged MVA, sustained:
Urine sample from CBD grew E. coli sensitive to ampicillin
�
Should we treat asymptomatic bacteriuria?
A retrospective study of > 2,700 patients with asymptomatic bacteriuria at 46 hospitals showed that antimicrobial treatment does not improve outcomes and is associated with longer hospitalization
Petty LA, Vaughn VM, Flanders SA, Malani AN, Conlon A, Kaye KS, Thyagarajan R, Osterholzer D, Nielsen D, Eschenauer GA, Bloemers S, McLaughlin E, Gandhi TN. Risk Factors and Outcomes Associated With Treatment of Asymptomatic Bacteriuria in Hospitalized Patients. JAMA Intern Med. 2019 Nov 1;179(11):1519-1527. doi: 10.1001/jamainternmed.2019.2871. PMID: 31449295; PMCID: PMC6714039.
Colgan R, Nicolle LE, McGlone A, Hooton TM. Asymptomatic bacteriuria in adults. Am Fam Physician. 2006;74(6):985-990.
“Patients with chronic indwelling Foley catheters are uniformly bacteriuric, but treatment is warranted only if the patient is symptomatic.”
3 things are certain in life: death, taxes and ……
There is always a trade-off when prescribing antibiotics
Readmitted to hospital after 1 month
CECT abdomen/pelvis
Revised report: No pneumoperitoneum
Complicated MRSA sepsis
Blood culture upon admission
ESBL sepsis
Blood cultures at ≈ 2nd week
CRE sepsis
Not available
Blood cultures at ≈ 3rd week
Invasive candidiasis
Blood cultures at ≈ 4th week
Case�reflections
COLLATERAL DAMAGE
Increased empirical polymyxin
High CRE / Acinetobacter MRO rates
Increased empirical carbapenem usage
High ESBL rates
Increased empirical 3rd gen cephalosporins usage
Resistance driving resistance
Is polymyxin a saviour drug?
Polymyxin is NOT a savior drug!!!
CLSI has taken the step to eliminate the “susceptible” interpretive category for the polymyxins
Clinical and PK/PD data demonstrate colistin and polymyxin B have limited clinical efficacy, even if an intermediate result is obtained. Alternative agents are strongly preferred. Colistin and polymyxin B should be used in combination with one or more active antimicrobial agents. Consultation with an infectious diseases specialist is recommended.
Novel antibiotics are:
Novel antibiotics
Tumbarello M, Trecarichi EM, Corona A, et al. Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae. Clin Infect Dis. 2019;68(3):355-364. doi:10.1093/cid/ciy492
Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival.
CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.
United States: Approved by the FDA in February 2015.
European Union: Approved by the European Medicines Agency (EMA) in June 2016.
United Kingdom, Sweden, France, Germany, Italy, Norway, Spain, Greece, Romania, Croatia, Denmark: Approved and launched between 2016 and 2020.
Ceftazidime-avibactam
The approval & accessibility of novel antibiotics in Malaysia often lag behind….
Not all CREs are the same.
KPC – America, Europe
NDM – India, SEA
We are at a clear disadvantage in the MDRO endgame!
Novel antibiotics like ceftazidime-avibactam
are promising against KPC,
but NOT against NDM.
>50% of our CRE in HRPB will not respond to ceftazidime-avibactam!
What can we do with NDM-producing CRE?
The use of CAZ-AVI + ATM was associated with lower 30-day mortality (HR, 0.37 [95% CI, .13–.74]; P = .01), lower clinical failure at day 14 (HR, 0.30 [95% CI, .14–.65]; P = .002), and shorter length of stay (HR, 0.49 [95% CI, .30–.82]; P = .007).
CAZ-AVI + ATM
Estimated cost: RM 12k + 3k for 2-week course
Cefiderocol had similar clinical and microbiological efficacy to best available therapy for infections caused by carbapenem-resistant Gram-negative bacteria.
Numerically more deaths occurred in the cefiderocol group, primarily in the patient subset with Acinetobacter spp infections.
Cefiderocol
Trojan horse antibiotics
Not available in Malaysia
AMR trend in Malaysia
Major AMR burden
In 2019 alone, 1.27 million people worldwide died from drug-resistant infections—a figure surpassing deaths from HIV/AIDS and malaria combined.
A cross-sectional study conducted in private primary care clinics in Malaysia found that only 42.9% of antibiotic prescriptions for acute pharyngitis were appropriate, while over 58.5% of prescriptions were deemed excessive.
A study examining URTI patients in an Emergency Department revealed that 29% of cases received inappropriate antibiotic prescriptions.
These are just the DIRECT impact of AMR…
The End of Antibiotics
The End of MODERN MEDICINE
“It has been recognized for several decades that up to 50% of antimicrobial use is INAPPROPRIATE.”
Given when not needed
Wrong antibiotic given
Broad spectrum to treat susceptible bacteria
Continued when no longer necessary
Given at wrong dose
IDSA/SHEA Guidelines for Antimicrobial Stewardship Programs
http://www.journals.uchicago.edu/doi/pdf/10.1086/510393
Antimicrobial Stewardship
(AMS)
HIT HARD UP FRONT
Timely appropriate antimicrobial therapy for severe infection to prevent mortality and morbidity
COLLATERAL DAMAGE
Avoid unnecessary broad spectrum antimicrobial use to prevent resistance and adverse effects
Empirical Antimicrobial Therapy
Narrow.
Short.
Oral.
Perak Hospitals
Smart Antibiotics Mantra
Use narrow-spectrum antibiotics
Keep antibiotic duration short
Switch to oral antibiotics early
Narrow.
Use narrow-spectrum antibiotics
Target ≥ 60%
Antibiotic PPS in HRPB 2022-2024
Unpublished data from Cheah MF
Choose the narrowest spectrum antibiotics
Follow local antimicrobial guidelines
https://sites.google.com/moh.gov.my/nag
Short.
Keep antibiotic duration short
Shorter is better….
Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection [published correction appears in N Engl J Med. 2018 Feb 15;378(7):686. doi: 10.1056/NEJMx180006.]. N Engl J Med. 2015;372(21):1996-2005. doi:10.1056/NEJMoa1411162
Short.
Keep antibiotic duration short
Oral.
Switch to oral antibiotics early
ORAL is the new IV
POET
OVIVA
SABATO
If the Gut works, consider oral!
Caveats to Short Duration / Early IV-to-Oral Switch
“Consult ID for choice and duration of antibiotics…..”
Antimicrobial Stewardship (AMS)
In the YEAR 2023
134 patients were reviewed by AMS team
AMS recommendations were given to primary teams:
79.9% AMS recommendations were ACCEPTED by primary teams
AMS Recommendation | Survived | Died |
ACCEPTED | 79.4% | 20.6% |
REJECTED | 77.8% | 22.2% |
AMS can achieve reduction in unnecessary antibiotic consumption without harm to patients.
Appropriate usage of antibiotics will reduce the risk of antimicrobial resistance (AMR).
AMS ward rounds are done regularly to optimize antimicrobial use among patients.
“Would accepting AMS recommendation cause harm to my patient?”
AMS is
SAFE, EFFECTIVE, and IMPORTANT !
Data collected and analysed by MF Cheah, AMS Pharmacist, HRPB
Between patients with AMS recommendation accepted or rejected, there is no significant difference in mortality outcome within 30 days (p=.797)
Please consult the AMS team if your patient is still receiving empiric carbapenem, vancomycin or quinolones for more than 72 hours.
Diagnostic Stewardship
Diagnostic stewardship
Diagnostic stewardship
68 yo man
Underlying DM and HTN
Presented with reduced consciousness
A/w poor oral intake
No fever
No SOB
No abdominal pain
BP: 120/80, PR: 80
Urine FEME: Leukocyte 2+, Nitrite +
Impression: Urosepsis
Plan
Start IV Unasyn 3gm tds
Admit medical
Hyponatremia due to thiazide
“Diagnosis begins with the patient, not the lab.”
Take appropriate cultures ONLY from possible source of infections
Swab culture?
Diagnostic stewardship
Infection Prevention and Control (IPC)
Infection Prevention & Control
IPC is essential to fight the development and spread of AMR.
Every infection prevented reduces the need for antimicrobials.
Infection Prevention & Control
Every lines and catheters increase RISK for hospital acquired infections!
DO NOT insert
if it’s not indicated.
REMOVE it
as soon as it’s not needed.
Infection Prevention & Control
Keep every equipment in ward clean.
All solution for patient and connection to patient’s IV access must be kept sterile.
Scrub the hub
In a nutshell….