A Publication of the Clinical and Translational Research Institute

Feature Article
Paving the Way Forward: The Medical City Antimicrobial
Stewardship Program
Karl Evans R. Henson and TMC Antimicrobial Stewardship Team*
Hospital Infection Control and Epidemiology Center, The Medical City, Ortigas Avenue, Pasig City
* Contact Details: [email protected]

Background
The discovery of penicillin in 1928 by Sir Alexander Carbapenem Resistance, All Isolates, ARSP
Fleming revolutionized the way physicians treat infections. 60

During his Nobel Lecture in 1945, however, Fleming 50

% Resistance
warned: “The time may come when penicillin can be 40
bought by anyone in the shops. Then there is the danger that 30
the ignorant man may easily underdose himself and by ex- 20
posing his microbes to non-lethal quantities of the drug
10
make them resistant.1” As more antimicrobials were dis-
0
covered throughout the years, we saw with almost mechan-
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
ical regularity the appearance of strains resistant to these
newly discovered drugs, with rates increasing the more the- Surveillance Years
se antibiotics were used. As the drug pipeline dried up and Klebsiella pneumoniae (Meropenem)
fewer novel molecules were discovered, attention now Pseudomonas aeruginosa (Meropenem)
turned to ensuring that these antimicrobials were used judi- Acinetobacter baumannii (Imipenem)
ciously. Figure 1. Carbapenem resistance of Klebsiella pneumoniae,
Pseudomonas aeruginosa, and Acinetobacter baumannii (all
A 2014 report from the United Kingdom on antimi- isolates) as reported in the Antimicrobial Resistance Surveillance
crobial resistance (AMR) estimated that there will be 10 Program (ARSP) from 2009 to 2018. The reported carbapenem for
A. baumannii is imipenem due to unavailability of meropenem
million people dying every year from resistant bacteria by DRAFT

susceptibility in the earlier reports

the year 2050 if nothing is done about it today.2 By then,
the worldwide cost related to AMR is projected to be as The Medical City (TMC) started restricting access to
much as US$100 trillion. The magnitude of AMR’s effect very broad-spectrum antimicrobials in the late 1990s. This
on people and economies led the World Health Assembly to early attempt at improving antimicrobial use is evidence of
endorse a Global Action Plan on AMR. Soon, AMR ap- TMC’s pioneering leadership role in AMS in the country.
peared on the agenda of almost every nation, including the In response to the global call against AMR, our own
Philippines. The 2018 Antimicrobial Resistance Surveil- government published the Philippine Action Plan to
lance Program (ARSP) report presents the sobering reality Combat Antimicrobial Resistance: One Health Approach in
that AMR is present in the Philippines as well (Figure 1). It 2016.5 Soon thereafter, the Department of Health required
is but fitting that all physicians should pay attention to this all hospitals in the country to create formal Antimicrobial
important crisis. Stewardship Programs (ASPs) as a requirement for
licensing and accreditation. Since TMC already had many
The main driver of antibiotic resistance is antibiotic initiatives in place that promoted antimicrobial stewardship,
consumption, whether appropriately or inappropriately the creation in 2016 of a formal Antimicrobial Stewardship
prescribed. Sun et al has demonstrated that the occurrence Committee focused on consolidating and expanding AMS
of resistant Escherichia coli and methicillin-resistant activities was a logical step
Staphylococcus aureus follows the curve of antibiotic
prescriptions for aminopenicillins and fluoroquinolones, Antimicrobial Stewardship: Definition and Rationale
respectively, with a lag of about one month (Figures 2A & Good AMS is a “practice that ensures the optimal
2B).3 In short, physician prescriptions directly affect selection, dose, and duration of an antimicrobial therapy
resistance rates. While there are many different factors that that leads to the best clinical outcome for the treatment or
affect AMR,4 the clearest and most direct one is prevention of infection while producing the fewest toxic
antimicrobial consumption. It is then incumbent upon all effects and the lowest risk for subsequent resistance.6” The
physicians to be careful about how they use antibiotics and fundamental challenge in AMS is the balancing act between
should consider these medicines a precious resource. This providing timely and appropriate empirical broad spectrum
need to rationalize the use of antimicrobials is what antimicrobial therapy for individual patients versus
antimicrobial stewardship (AMS) is all about. reducing unnecessary use of these same agents and their
subsequent collateral damage.7,8

The Medical City Journal (December 2019): Volume 2 Issue 1 57

The Medical City Journal © 2019

DRAFT

Figure 2. (A) Seasonal pattern of high-usage antibiotic prescriptions and Escherichia coli (E. coli) resistance, showing 1-month lag; (B)
Seasonal pattern of antibiotic prescriptions and Methicillin-Resistant Staphylococcus aureus (MRSA), showing 1-month lag. Figures re-
printed with permission from Oxford University Press (Sun et al., Seasonality and Temporal Correlation between Community Antibiotic
Use and Resistance in the United States, 2012, 55(5): 690-691)

Schuts et al examined the existing evidence for 9 associated with a 15% increase in compliance with desired
AMS objectives using four pre-defined outcomes: clinical practice, a 1.95-day decrease in treatment duration, and a
outcomes (mortality and morbidity), adverse events, cost, 1.12-day decrease in inpatient length of stay without
and resistance rates.9 While they cite generally low quality compromising patient safety.
of evidence and moderate to high heterogeneity between
studies, they found that guidelines-based empirical therapy, Components of the TMC Antimicrobial Stewardship
de-escalation of therapy, switch from intravenous to oral Program
treatment, therapeutic drug monitoring, antimicrobial In November 2017, the leadership of TMC approved
restriction, and bedside consultation resulted in significant the policy governing all aspects of antimicrobial utilization
benefits for one or more of the 4 outcomes. in our institution. The policy was patterned after the DOH’s
own Manual of Operations for Antimicrobial Stewardship,12
Honda et al examined inpatient AMS in the Asia with revisions meant to adopt various components to the
Pacific Region.10 Using 4 outcomes (clinical, antimicrobial culture of TMC. Some of the most practical components of
prescription, microbiology, and expenditure), the authors the program, as well as its objectives, are described below.
reviewed the results of 46 studies from 9 countries. Their
meta-analysis demonstrated that ASPs resulted in TMC Antimicrobial Use Guidelines (Empiric
significant reductions in antimicrobial and carbapenem Recommendations, Surgical Prophylaxis). The hospital’s
consumption and trends toward decreased incidence of antibiogram is one of the most important tools used in
multidrug-resistant organisms and antimicrobial AMS. Aside from informing physicians about which
expenditure. Consistent with the previous reviews, this organisms are most common in the hospital, classified by
study showed no significant mortality increase with ASPs. source (blood, urine, respiratory secretions, etc) and by
location (outpatient, inpatient wards, and critical care units,
The most recent Cochrane Review of hospital-based (Figure 3A), the antibiogram also reports on susceptibility
interventions to improve antibiotic prescribing practices11 patterns of these organisms (Figure 3B). The idea is to
showed that enabling and restrictive methods were allow the physicians to make educated decisions about

58
 A Publication of the Clinical and Translational Research Institute

empiric therapy for individual patients. At TMC, the

information from the local antibiogram is synthesized with
the recommendations from the National Antibiotic
Guidelines Committee (NAGCOM), a multidisciplinary Drug Duration Audit and Feedback (DDAF or
group of experts tasked to review existing local and Automatic Stop Order). There is a growing body of
international guidelines and formulate a unified document evidence that for most infections, a short course of
to be used by healthcare institutions in the country. 13 The antimicrobials is as effective as the traditional longer
resulting document, TMC’s Antimicrobial Use Guidelines, courses.14 Short courses of antimicrobials result in less
is reviewed and published annually (Table 1) to guide adverse effects, such as Clostridioides difficile infections,
physicians in the management of the most common lower cost, and better outcomes. The DDAF is our attempt
infections and in making wise choices for surgical antibiotic to remind the medical staff to frequently evaluate the need
prophylaxis. for continued antibiotics in individual patients. DDAF is
currently in effect only in critical care units but will soon be
implemented hospital-wide in accordance with directives
from the DOH.

Prospective Audit of Monitored Antimicrobials with

Direct Feedback. TMC was one of a handful of Philippine
hospitals participating in the Global Point Prevalence
Survey on Antimicrobial Consumption and Resistance.15 In
this survey, we found that 53% of inpatients at our
institution are on antimicrobials at any given time. 16 This is
a staggering figure since worldwide average is only around
31%.17 In addition, 43% of our antimicrobial usage did not
adhere to NAGCOM guidelines. In an attempt to optimize
utilization of antimicrobials at the point of care, the HICEC
Executive Committee created a list of 8 “monitored”
DRAFT
antimicrobials derived from the most commonly used
antibiotics based on the results of our prevalence survey.
Prescription of these monitored antimicrobials will trigger
the AMS Team (composed of the AMS Committee Chair or
ID fellow and AMS clinical pharmacists) to review the
patient’s chart and to make one or more of the following
recommendations: intravenous-to-oral therapy switch, dose
optimization, and streamlining or de-escalation.
Implementation of this initiative will be in phases and will
begin with one or more medical floors with plans for
hospital-wide expansion.

Prior Approval of Restricted Antimicrobials (PARA).

This stewardship initiative has been in place in one form or
another since the late 1990s. In its current form, the list of
restricted antimicrobials include: amphotericin B,
anidulafungin, cefepime, colistin (polymyxin E),
daptomycin, ertapenem, ganciclovir, imipenem, linezolid,
meropenem, polymyxin B, tigecycline, valganciclovir, and
vancomycin. Prescription of these medications by a non-ID
Figure 3. (A) Seasonal TMC Antibiogram January to June 2019, physician must be accompanied by documentation of
top 5 organisms by hospital location; (B) TMC Antibiogram,
intermediate susceptibility and resistance patterns of Klebsiella
approval from an ID consultant. This will ensure that the
pneumoniae (respiratory isolates obtained from inpatients); AMC- broadest spectrum antimicrobials (and hence the most
amoxicillin-clavulanic acid, TZP- piperacillin-tazobactam, CXM- precious) are used appropriately and judiciously. This
cefuroxime; CRO- ceftriaxone, ETP- ertapenem, FEP- cefepime, stewardship initiative is implemented hospital-wide.
IPM- imipenem, MEM- meropenem, AMK- amikacin, LVX-
levofloxacin, CAZ- ceftazidime, CST- colistin, SXT-
trimethoprim-sulfamethoxazole

The Medical City Journal (December 2019): Volume 2 Issue 1 59

The Medical City Journal © 2019

Table 1. The Medical City Empiric Antimicrobial

Recommendations 2019 Future Direction
Pneumonia
Community-acquired pneumonia- MODERATE RISK
Except for the PARA initiative, implementation of the
- Ampicillin-sulbactam 1.5g IV every 6 hours OR components of the AMS program are in place only in
- Ceftriaxone 2g IV once a day selected areas of the hospital. In order to ensure that TMC
PLUS
 Azithromycin 500mg PO once a day OR remains a good steward of these precious antimicrobials
 Clarithromycin 500mg PO twice a day OR and maintain its leadership in this field, the program
 Levofloxacin 750mg PO once a day
Community-acquired pneumonia- HIGH RISK, without risk factors for P.
components have to be implemented hospital-wide. For this
aeruginosa to occur, hospital leadership needs to invest in the hiring
- Ceftriaxone 2g IV once a day OR and training of additional staff (both clinical pharmacists
- Ertapenem 1 g IV once a day
PLUS and nurses) with a heart for AMS. Transitioning to a new
 Azithromycin dehydrate 500mg IV once a day OR electronic record with the capacity to automatically
 Levofloxacin 750mg IV once a day
Community-acquired pneumonia- HIGH RISK, WITH risk factors for P.
generate AMS-related reports should also allow the AMS
aeruginosa team to streamline its workflow and devote more time to
- Piperacillin-tazobactam 4.5g IV every 6hours OR interacting with the medical teams (i.e. audit and feedback)
- Cefepime 2 g IV every 8-12h
PLUS rather than tedious data collection.
 Azithromycin 500mg IV once a day
PLUS
 Amikacin 15mg/kg IV once a day
With a national government bent on ensuring
Community-acquire pneumonia- HIGH RISK with suspicion of MRSA, implementation of an AMS program nationwide in the next
ADD: few years, there is a flurry of activity in both the public and
- Vancomycin 25-30 mg/kg IV loading dose then 15-20 mg/kg
every 8-12 hours OR private sectors to ensure compliance with newly established
- Linezolid 600mg IV every 12 hours OR policies. For many healthcare institutions, especially the
- Clindamycin 600mg IV every 8 hours
HAP/ VAP- inpatient, no risk factors for MDR organisms (e.g. A. smaller hospitals unfamiliar with the concepts of AMS, this
baumannii) means sending staff to training seminars and multiple
- Piperacillin-tazobactam OR Cefepime OR Meropenem ± strategic planning sessions. Because our institution has
- Amikacin 15mg/kg IV once a day
Pneumonia other than CAP- inpatient with risk factors for MDROs (e.g. A. invested in AMS for many years, we find ourselves in a
baumannii) somewhat mentorship role in the midst of all this activity.
- Immediate referral to ID recommended
Pneumonia other than CAP- inpatient, non-ICU, with risk factors for DRAFT
Beginning in 2016, some of our leaders in the Section of
MRSA or aspiration Infectious Diseases have been heavily involved in the
- Add Clindamycin
Pneumonia other than CAP- inpatient, ICU with risk factors for MRSA
DOH-sponsored training of hospitals in AMS. In 2016, we
- Add Vancomycin OR Linezolid hosted two clinical pharmacists in the maiden run of a
Urinary Tract Infections clinical pharmacy fellowship for AMS. It is evident that our
Acute cystitis commitment to building the national AMS program is
- Nitrofurantoin
Acute uncomplicated pyelonephritis resolute and our role in the national AMS program is an
- Ceftriaxone embodiment of our hospital’s mission to take a leadership
In-patients (hospital acquired):
- Without risk factors for ESBL producing organisms: role in shaping how the nation thinks, feels, and behaves
 Piperacillin-tazobactam OR Amikacin about health.
- With risk fac tors for ESBL producing organisms:
 Ertapenem OR Amikacin
Skin and Soft Tissue Infections
More than all the AMS-related programs and policies
Caveat: the vast majority of non-purulent SSTI (i.e. no microbiologic data
in place, the core need of a good antimicrobial stewardship
available) is due to Streptococci campaign is behavioral change and a paradigm shift among
Community acquired, localized, without signs of sepsis: antibiotic prescribers. AMR has been called a “slow
- Clindamycin OR
- Doxycycline OR moving catastrophe4” because it is less acute and less
- Cotrimoxazole (no good Streptococcal coverage) glamorous than ebola or epidemic influenza. But AMR is
Nosocomial and/ or with signs of sepsis:
- Vancomycin OR just as deadly. The families of patients affected by
- Linezolid infections caused by multidrug resistant organisms
PLUS
 Piperacillin-tazobactam
(MDROs) know all too well how lethal these bacteria can
Azithromycin FDA Drug Safety Communication be. There is a mountain of evidence showing that antibiotics
1. FDA warns about increased risk of cancer relapse with long are overprescribed and abused, despite well-written,
term use of azithromycin after donor stem cell transplant evidence-based guidelines. Unless antibiotic prescribers
(8/3/2018)
2. Azithromycin and the risk of potentially fatal heart rhythms stop thinking small (i.e. just their own patients) and start
(3/12/2013) thinking with a global mindset, antibiotics will continue to
Levofloxacin FDA Drug Safety Communication be overused. There are many different things physicians can
1. FDA warns about increased risk of ruptures or tears in the
aorta blood vessel in certain patients (12/20/2018) do to reduce inappropriate antibiotic use. 4 The common
2. FDA is strenghthening the current warnings in the prescribing theme in all these should be a basic understanding of why
information that fluoroquinolone antibiotics may cause
significant decrease in blood sugar and certain mental health things need to change.
side effects (7/10/2018)

60
 A Publication of the Clinical and Translational Research Institute

[6] Owens RC. Antimicrobial Stewardship: Concepts and Strategies in the

21st Century. Diagn Microbiol Infect Dis. 2008;61(1):110-128.
Antibiotics are one of the most commonly prescribed
[7] Dellit TH, Owens RC, McGowan JE, et al. Infectious Diseases Society
types of medication and their use cuts across all specialties. of America and the Society for Healthcare Epidemiology of
If we lose this precious resource to over-prescription and America Guidelines for Developing an Institutional Program to
abuse, we may bring the world back to an era when Enhance Antimicrobial Stewardship. Clinical Infectious
Diseases. 2007;44(2):159-177.
penicillin was unavailable, and patients died from the
[8] Davey P, Sneddon J, Nathwani D. Overview of Strategies for
simplest of infections. All physicians must recognize their Overcoming the Challenge of Antimicrobial Resistance. Expert
critical role as stewards of antibiotics and should work to Rev Clin Pharmacol. 2010;3(5):667-686.
ensure that these drugs are used properly and judiciously. [9] Schuts EC, Hulscher MEJL, Mouton JW, et al. Current Evidence on
Hospital Antimicrobial Stewardship Objectives: A Systematic
Review and Meta-Analysis. Lancet Infect Dis. 2016;16(7):847-
856.
THE MEDICAL CITY ANTIMICROBIAL STEWARDSHIP TEAM [10] Honda H, Ohmagari N, Tokuda Y, Mattar C, Warren DK.
Antimicrobial Stewardship in Inpatient Settings in the Asia
Chair: Karl Evans R. Henson, MD Pacific Region: A Systematic Review and Meta-analysis.
Clinical Infectious Diseases. 2017;64(suppl_2):S119-S126.
AMS Specialist: Maria Katrina D. Rayos, RPh [11] Davey P, Marwick CA, Scott CL, et al. Interventions to Improve
Antibiotic Prescribing Practices for Hospital Inpatients.
Senior Stewardship Consultant: Mediadora C. Saniel, MD Cochrane Database Syst Rev. 2017;2:CD003543.
[12] Department of Health. Antimicrobial Stewardship Program in
Infectious Disease Consultants: Hospitals Manual of Procedures. March 2017:1-82.
Maria Fe R. Tayzon, MD [13] Department of Health. National Antibiotic Guidelines 2017.
Mary Ann D. Lansang, MD November 2017:1-264.
Regina P. Berba, MD [14] Royer S, DeMerle KM, Dickson RP, Prescott HC. Shorter Versus
Marissa M. Alejandria, MD Longer Courses of Antibiotics for Infection in Hospitalized
Cybele Lara R. Abad, MD Patients: A Systematic Review and Meta-Analysis. J Hosp
Raul V. Destura, MD Med. January 2018:E1-E7.
Marja B. Buensalido, MD [15] Goossens H, Nathwani D. Global Point Prevalence Survey on
Cynthia A. Aguirre, MD Antimicrobial Consumption and Resistance.
Sarah R. Makalinaw, MD [16] Henson KER, Rayos MD, Geronimo MC. Global Point Prevalence
Survey on Antimicrobial Consumption and Reistance: The
Infectious Disease Fellows: Medical City Data. 2017.
Jan Jorge M. Francisco, MD [17] Versporten A, Drapier N, Zarb P, et al. The Global Point Prevalence
Jia An G. Bello, MD Survey of Antimicrobial Consumption and Resistance (Global-
DRAFT

PPS): A Worldwide Antimicrobial Web-Based Point

Clinical Pharmacists: Prevalence Survey. Open Forum Infectious Diseases.
Charity M. Nadal, RPh 2015;2(Suppl 1).
Clarissa Jane S. Sarmiento, RPh [18] Karanika S, Paudel S, Grigoras C, Kalbasi A, Mylonakis E.
Molyn B. Nunez, RPh Systematic Review and Meta-analysis of Clinical and
Raquel Guia Grace C. Macaparra, RPh Economic Outcomes from the Implementation of Hospital-
Based Antimicrobial Stewardship Programs. Antimicrobial
Agents and Chemotherapy. 2016;60(8):4840-4852.
[19] Morris AM. Antimicrobial Stewardship Programs: Appropriate
REFERENCES Measures and Metrics to Study their Impact. Curr Treat
[1] Fleming A. Penicillin, 1945:1-11.
Options Infect Dis. 2014;6(2):101-112.
[2] UK Report: Review on Antimicrobial Resistance. Antimicrobial
[20] World Health Organization, Methodology WIWGFDS, World Health
Resistance: Tackling a Crisis for the Health and Wealth of
Organization. WHO Collaborating Center for Drug Statistics
Nations. 2014:5-7.
Methodology. WHO Collaborating Center for Drug Utilization
[3] Sun L, Eili YK, and Laxminarayan R. Seasonality and Temporal
Research and Clinical Pharmacological Services. Introduction
Correlation between Community Antibiotic Use and Resistance
to Drug Utilization Research. 2003.
in the United States. Clin Infect Dis. 2012;55(5):687-94.
[21] Laxminarayan R, Klugman KP. Communicating Trends in Resistance
[4] Lesho EP and Laguio-Vila M. The Slow-Motion Catastrophe of
Antimicrobial Resistance and Practical Interventions for All using a Drug Resistance index. BMJ Open. 2011;1(2):e000135-
Prescribers. Mayo Clin Proc, 2019;94(6):1040-7. e000135.
[5] Department of Health. The Philippine Action Plan to Combat
Antimicrobial Resistance: One Health Approach. November
2015:1-40.

The Medical City Journal (December 2019): Volume 2 Issue 1 61