Guide Line National Guidance For Antimicrobial Use in Infections Mdros

Guideline
Central Administration of Pharmaceutical Care
General Administration For Drug Utilization &Pharmacy Practice
National Guidance for Antimicrobial Use in Infections with

Multi-Drug Resistant Organisms (MDROs)
2024
National Rational Antimicrobial Use Committee
Code: EDREX:GL.CAP.Care.026
Version No: 1
Issue Date: May 2024
National Guidance for Antimicrobial Use in Infections with Multi-Drug

Resistant Organisms
1 Code: EDREX:GL.CAP.Care.026
Version no: 1 Issue date: May 2024
Guideline
Table of Contents
Introduction.................................................................................................................................................................. 3
The Scope of the Guidance.......................................................................................................................................... 3
Abbreviations ............................................................................................................................................................... 3
The burden of antimicrobial resistance (AMR) on the global level ........................................................................ 4
The Antimicrobial Consumption Data (AMC) in Egypt .......................................................................................... 4
The Most problematic antibiotic-resistant bacteria in healthcare facilities ........................................................... 4
Multi-resistant Gram-negative bacilli (MRGN) ....................................................................................................... 5
Definitions of MDR, XDR and PDR for different MRGN ....................................................................................... 5
Colonization Versus True Infection ........................................................................................................................... 9
Acinetobacter baumannii .......................................................................................................................................... 11
Enterobacteriaceae .................................................................................................................................................... 11
Pseudomonas aeruginosa .......................................................................................................................................... 22
Stenotrophomonas maltophilia................................................................................................................................. 25
Multi-resistant Gram-positive cocci ......................................................................................................................... 25
Vancomycin-resistant Enterococci (VRE) ............................................................................................................... 25
Suggested dosing of antibiotics for the treatment of infections caused by antimicrobial resistant organism ... 26
Duration of therapy for common clinical syndromes ............................................................................................. 28
References................................................................................................................................................................... 29
Contributors ............................................................................................................................................................... 31

Resistant Organisms
Guideline
Introduction
Antimicrobial resistance is the capability of a microorganism to resist the action of the different
antimicrobials that could once be successful against them. When this resistance occurs to multiple drugs,
it is known as multidrug resistance (MDR). There are different types of resistance mechanisms observed
in microbes, like natural resistance in certain microbes against a particular antimicrobial, genetic
mutation, or acquired resistance from other species. (1)
As per the statement of World Health Organization (WHO), MDR pathogens called ‘superbugs’ are one
of the major public threats that yearly cause several million deaths globally. (1)
Antimicrobial resistance occurs as a direct result of antibiotic treatment, the abuse and misuse of
antibiotics for the treatment, prevention, or management of diseases in people, animals, and plants. (2),(3)
Contributing factors include lack of access to clean water, sanitation, and hygiene (WASH) for both
humans and animals; poor infection and disease prevention and control in homes, healthcare facilities
and farms; poor access to quality and affordable vaccines, diagnostics, and medicines; lack of awareness
and knowledge; and lack of enforcement of relevant legislation. (3)
Several operations, such as hip replacements, organ transplants, cesarean sections, and other surgeries,
become at risk due to the introduction and spread of drug-resistant bacteria. (3)
AMR has significant costs for both health systems and national economies overall. For example, it
creates need for more expensive and intensive care, affects productivity of patients or their caregivers
through prolonged hospital stays, and harms agricultural productivity. (3)
AMR is a problem for all countries at all income levels. Its spread does not recognize country
borders. People living in low-resource settings and vulnerable populations are especially impacted by
both the drivers and consequences of AMR. (3)
The Scope of the Guidance
To describe appropriate antimicrobial chemotherapy for infections due to MDROs.
To describe best practices in antimicrobial prescribing including antimicrobial agents that are available
in Egypt.
To serve as a clinical guide and not supersede the clinical judgment of physicians in the management of
individual patients.
Abbreviations
A. baumannii Acinetobacter. baumannii

AMC Antimicrobial Consumption
AMR Antimicrobial Resistance
CDC Centre for Disease Prevention and Control
CFU Colony Forming Units
CRAB Carbapenem-Resistant Acinetobacter baumannii
CRE Carbapenem- Resistant Enterobacterales
DTR-PA Difficult-to-Treat P.aeruginosa
ESBL Extended-spectrum beta-lactamases
GLASS Global Antimicrobial Resistance and Use Surveillance System
IDSA Infectious Diseases Society of America
KPC Klebsiella pneumoniae carbapenemase
MBL Metallo-beta-lactamases
MDROs Multidrug-resistant organisms
MRGN Multi-resistant Gram-negative bacilli
NDM New Delhi MBL
PA Pseudomonas aeruginosa
Resistant Organisms
Guideline
PDR Pan- Drug Resistant
UTI Urinary Tract Infection
VRE Vancomycin-Resistant Enterococci
VAP Ventilator Acquired Pneumoiae
VIM Verona integron-encoded MBL
TMP-SMX Trimethoprim- sulfamethoxazole
WHO World Health Organization
XDR Extensively drug-resistant
The burden of antimicrobial resistance (AMR) on the global level

The global rise in antibiotic resistance poses a significant threat, diminishing the efficacy of common
antibiotics against widespread bacterial infections. (3)
The 2022 Global Antimicrobial Resistance and Use Surveillance System (GLASS) report highlights alarming
resistance rates among prevalent bacterial pathogens. Median reported rates in 76 countries of 42% for
third-generation cephalosporin-resistant E. coli and 35% for methicillin-resistant Staphylococcus
aureus are a major concern. For urinary tract infections caused by E. coli, 1 in 5 cases exhibited reduced
susceptibility to standard antibiotics like ampicillin, co-trimoxazole, and fluoroquinolones in 2020. This
is making it harder to effectively treat common infections. (3)
Klebsiella pneumoniae, a common intestinal bacterium, also showed elevated resistance levels against
critical antibiotics. Increased levels of resistance potentially lead to heightened utilization of last-resort
drugs like carbapenems, for which resistance is in turn being observed across multiple regions. As the
effectiveness of these last-resort drugs is compromised, the risks increase of infections that cannot be
treated. Projections by the Organization for Economic Cooperation and Development (OECD) indicate
an anticipated twofold surge in resistance to last-resort antibiotics by 2035, compared to 2005 levels,
emphasize the urgent need for robust antimicrobial stewardship practices and enhanced surveillance
coverage worldwide. (3)
AMR represents a global challenge, 4.95 million people who died in 2019 suffered from drug-resistant
infections, AMR directly caused 1.27 million of those deaths, 1 in 5 of those deaths occurred among
children under 5 years old. (4)
The Antimicrobial Consumption Data (AMC) in Egypt
The recent analysis of the national AMC data for 2022 indicates that the consumption according to the
AWaRe list was as follows - Access group 55.52%, Watch group 42.86%, and Reserve group 0.96%.
According to the GLASS-AMC report, penicillins make up the majority of Egypt's antimicrobial
consumption; products containing a combination of penicillins and beta-lactamase inhibitors make up
29.3% of the antibacterials used, while macrolides make up 23.93%.
The Most problematic antibiotic-resistant bacteria in healthcare facilities
In 2021, WHO published the list of antibiotic-resistant pathogens (priority pathogens), especially
highlighting the resistant gram-negative bacteria that pose maximum threat to human health. On the
basis of urgency for new antibiotics, the list is categorized into three headings, mainly critical, high, and
medium priority. (1)
The critical group of MDR bacteria includes Pseudomonas aeruginosa, Acinetobacter baumannii, and
Enterobacteriaceae, which cause severe infections like pneumonia and blood stream infections in
hospital-admitted patients. The high and medium priority group include drug-resistant bacteria like
Salmonella that causes common diseases, such as gonorrhoea and food poisoning. (1)

Resistant Organisms
Guideline
Multi-resistant Gram-negative bacilli (MRGN)
Gram-negative bacilli are a large group of bacteria that are commonly found in the intestinal tract of
humans and most animals. They form part of the normal microflora and are essential for proper digestive
processes. However, these bacteria can cause infection when introduced into normally sterile body sites,
such as the bladder or deep tissues, particularly via the insertion of a medical device or during surgery.
(2),(5),(6)
Serious infections require the administration of antibiotics and can be associated with a high mortality
rate, particularly in vulnerable patients such as those in critical care or who are immune-suppressed.
(2),(6)
The term, “ESKAPE,” has been proposed to express the majority of nosocomial infections due to
resistant pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,
Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. (7)
Resistance in Gram-negative bacilli occurs by several mechanisms and there are literally dozens of
different resistance determinants. Those that pose particular problems for hospital patients can be
broadly grouped into: (2)
- Transferable beta-lactam resistance, for example AMP-C, mostly found in E. coli and Salmonella
species.
- Extended-spectrum beta-lactamases (ESBL)– transferable resistance to 3rd and 4th generation
cephalosporins, mostly found in E. coli, Klebsiella and Enterobacter species.
- Metallo-beta-lactamases (MBL) – similar to ESBL, but can also include resistance to
carbapenems, mostly found in Pseudomonas aeruginosa.
- Carbapenemase-producing Enterobacterales (formerly known as Carbapenemase-producing
Enterobacteriaceae), an emerging resistance of concern.
The increased threat from Gram-negative MDR species is widely acknowledged by global and
national organizations including the WHO, European Centre for Disease Prevention and Control
(CDC), Infectious Diseases Society of America (IDSA), and the United States CDC. Indeed, among
the WHO’s list of priority resistant bacteria for 2016–17, three are described as critical—the highest
level of concern—and all three are Gram-negative, namely Carbapenem resistant
Enterobacterales, Carbapenem-resistant A. baumannii, and Carbapenem-resistant P.
aeruginosa (5)
Definitions of MDR, XDR and PDR for different MRGN

It is the general method for classifying AMR for different types of bacteria, but the treatment
recommendations mentioned in the guidance are built up based on the resistance gene/ enzyme mutation.
Table 1: Definition of MDR, XDR and PDR Acinetobacter (8)
Resistance category Criteria for defining
Non-susceptible to: ≥ 1 agent in ≥ 3 antimicrobial categories but still
susceptible to agent/s in more than 2 categories from table 2.
Example: resistance to:
MDR One or more agents of the Aminoglycoside category
One or more agents of the antipseudomonal Carbapenem category
One or more agents of the antipseudomonal Cephalosporins
Non-susceptible to ≥1 agent in all categories except 2 or fewer
XDR antimicrobial categories from table 2.

Resistant Organisms
Guideline
One or more agent of the Aminoglycoside category
One or more agent of the antipseudomonal Carbapenem category
One or more agent of the Extended spectrum Cephalosporins
One or more agent of antipseudomonal Fluoroquinolones category
Piperacillin/ tazobactam of the antipseudomonal Penicillin category
Fosfomycin of Phosphoric acids category, Tetracycline, Colistin,
Trimethoprim-sulphamethoxazole.
Non-susceptibility to all agents in all antimicrobial categories for each
bacterium in the table 2.
PDR
Table 2: Susceptibility of Acinetobacter baumannii (8)

Antimicrobial category Antimicrobial agent
Gentamicin
Aminoglycosides Tobramycin
Amikacin
Antipseudomonal Imipenem
carbapenems Meropenem
Cefotaxime
Extended spectrum Ceftriaxone
cephalosporins Ceftazidime
Cefepime
Antipseudomonal Ciprofloxacin
fluoroquinolones Levofloxacin
Antipseudomonal
penicillin/ β- lactamase Piperacillin-tazobactam
inhibitors
Folate pathway inhibitors Trimethoprim-sulphamethoxazole
Monobactams Aztreonam
Penicillins + b-lactamase
Ampicillin-sulbactam
inhibitors
Phosphoric acids Fosfomycin
Colistin
Polymyxins
Polymyxin B
Tetracycline
Tetracyclines Doxycycline
Minocycline
Table 3: Definition of MDR, XDR and PDR Enterobacteriaceae (8)

Non-susceptible to: ≥ 1 agent in ≥ 3 antimicrobial categories but still
MDR
susceptible to agent/s in more than 2 categories from table 4.
XDR
antimicrobial categories from table 4.
PDR
bacterium in the table 4.

Resistant Organisms
Guideline
Table 4 Enterobacteriaceae; antimicrobial categories and agents used to define MDR, XDR
and PDR(8)
Antimicrobial category Antimicrobial agent Species with intrinsic resistance to
antimicrobial agents or categories
Gentamicin Providencia rettgeri (P. rettgeri),
Aminoglycosides Tobramycin Providencia stuartii (P. stuartii)
Amikacin
Ceftaroline (approved only
Anti-MRSA for: Escherichia coli,
cephalosporins Klebsiella pneumoniae,
Klebsiella oxytoca)
Ertapenem
Carbapenems Imipenem
Meropenem
Citrobacter freundii (C. freundii),
Enterobacter aerogenes (E. aerogenes),
Enterobacter cloacae (E. cloacae),
Non-extended spectrum Hafnia alvei (H. alvei), Morganella
Cefazolin
cephalosporins; 1st and morganii (M. morganii), Proteus penneri
2nd generation (P. penneri), Proteus vulgaris (P.
cephalosporins vulgaris), P. rettgeri, P. stuartii, Serratia
marcescens (S. marcescens)
M. morganii, P. penneri, P. vulgaris, S.
Cefuroxime
marcescens
Cefotaxime
Extended spectrum Ceftriaxone
cephalosporins Ceftazidime
Cefepime
C. freundii, E. aerogenes, E. cloacae, H.
Cephamycins Cefoxitin
alvei
Fluoroquinolones Ciprofloxacin
Antipseudomonal
penicillin/ β- lactamase Piperacillin-tazobactam Escherichia hermannii (E. hermanii)
inhibitors
Trimethoprim-
Folate pathway inhibitors
sulphamethoxazole
M. morganii, Proteus mirabilis (P.
Glycylcyclines Tigecycline mirabilis), P. penneri, P. vulgaris, P.
rettgeri, P. stuartii
Citrobacter koseri (C. koseri), C.
freundii, E. aerogenes, E. cloacae, E.
Penicillins Ampicillin hermanii, H. alvei, Klebsiellae spp., M.
morganii, P. penneri, P. vulgaris, P.
rettgeri, P. stuartii, S. marcescens
C. freundii, C. koseri, E. aerogenes, E.
Penicillins + b-lactamase
Ampicillin-sulbactam cloacae, H. alvei, P. rettgeri, S.
inhibitors
marcescens

Resistant Organisms
Guideline
C. freundii, E. aerogenes, E. cloacae, H.
Amoxicillin-clavulanic acid alvei, M. morganii, P. rettgeri, P. stuartii,
S. marcescen
M. morganii, P. mirabilis, P. penneri, P.
Polymyxins Colistin vulgaris, P. rettgeri, P. stuartii, S.
marcescens
M. morganii, P. mirabilis, P. penneri, P.
Tetracycline
vulgaris, P. rettgeri, P. stuartii
Tetracyclines
Doxycycline M. morganii, P. penneri, P. vulgaris, P.
Minocycline rettgeri, P. stuartii
Table 5: Definition of MDR, XDR and PDR Pseudomonas aeruginosa (8)

Non susceptible to: ≥ 1 agent in ≥ 3 antimicrobial category but still
susceptible to more than 2 categories from table6.
MDR
One or more agents of the aminoglycoside category
One or more agents of the antipseudomonal carbapenem category
One or more agents of the antipseudomonal cephalosporins
antimicrobial categories in table 6.
One or more agents of the aminoglycoside category
XDR One or more agents of the antipseudomonal carbapenem category
One or more agents of the antipseudomonal cephalosporins
One or more agents of antipseudomonal fluoroquinolones category
Piperacillin/ tazobactam of penicillin category
Fosfomycin of Phosphoric acids category
PDR
bacterium in the table 6
Table 6: Antimicrobial categories and agents used to define MDR, XDR and PDR Pseudomonas
aeruginosa(8)
Antimicrobial category Antimicrobial agent
Gentamicin
Aminoglycosides Tobramycin
Amikacin
Imipenem
Antipseudomonal carbapenems
Meropenem
Ceftazidime
Antipseudomonal cephalosporins
Cefepime
Ciprofloxacin
Antipseudomonal fluoroquinolones
Levofloxacin
Antipseudomonal penicillin/ β-
Piperacillin-tazobactam
lactamase inhibitors
Polymyxins Colistin- Polymyxin B

Resistant Organisms
Guideline
Colonization Versus True Infection
MDROs infections e.g., CRAB are most commonly recovered from respiratory specimens or wounds.
Therefore, it is not always clear if an isolate is a colonizing organism in patients who are ill for reasons
attributable to their underlying host status (e.g., patients requiring mechanical ventilation, patients with
extensive burns), or if CRAB represents a true pathogen capable of contributing to excess mortality,
leading to uncertainty about the need for antibiotic therapy. For the same reason, it is challenging to
determine if poor clinical outcomes are attributable to suboptimal antibiotic therapy or underlying host
factors. (9)
Table 7: Difference between colonization and true infection
Colonization Infection
It is the presence of bacteria on a body surface It is the invasion of a host organism's bodily tissues
(like on the skin, mouth, intestines or airway) by disease-causing organisms. Infection also
without causing disease for the person.(10) results from the interplay between pathogens and
the defenses of the hosts they infect.(10)
Isolates were classified as colonization when no Infections were defined by the presence of a major
adverse clinical signs or symptoms were bacterial load associated with clinical
(11)
documented. manifestations within the infection window period
(±3 days from specimen collection). (11)
The most important factor in determining if a patient is colonized or infected with an organism is the
clinical picture.(12)
One must put together the pieces of the puzzle that constitute the clinical picture and the following
factors to determine if antimicrobials should be started. (12)
- Method by which sample obtained
- Gram stain results
- Culture results
- Body temperature
- Radiographic findings
- Change in oxygenation or ventilation status
- Underlying medical conditions
- Results of white blood cell count & differential
- General clinical condition
Table 8: Diagnostic criteria for infections (11)

Infection Site of Culture Bacterial Load Clinical Signs
Fever/chills/hypotension
Primary Blood 2 percutaneous blood
+
Stream samples + eventual blood
No further sign of localized
Infection from catheters
infection
• If Common Commensal organisms (i.e., diphtheroids (Corynebacterium spp. not C. diphtheria),
Bacillus spp. (not B. anthracis), Propionibacterium spp., coagulase-negative staphylococci

Resistant Organisms
Guideline
(including S. epidermidis), viridans group streptococci, Aerococcus spp. Micrococcus spp. and
Rhodococcus spp.): necessary two or more blood specimens drawn on separate occasions.
Central line- percutaneous blood samples Fever/chills/hypotension
associated + catheter blood or catheter +
Blood Stream tip No further sign of localized
Infection infection. Eventual erythema,
(at least 48 h swelling, purulent drainage from
after catheter catheter insertion-site.
positioning)
• Central line colonization: positive catheter blood or catheter tip and negative percutaneous blood
samples.
• If Common Commensal organisms (i.e., diphtheroids (Corynebacterium spp. not C. diphtheria),
Bacillus spp. (not B. anthracis), Propionibacterium spp., coagulase-negative staphylococci
(including S. epidermidis), viridans group streptococci, Aerococcus spp. Micrococcus spp. and
Rhodococcus spp.): necessary two or more blood specimens drawn on separate occasions.
Bronchoalveolar lavage ≥104 Colony 1 of:
Ventilator-
forming units fever, leukocytosis/leucopenia.
associated
(CFU)/mL +
lower
Endotracheal Aspirate ≥105 CFU/mL 1 of:
respiratory
secondary Blood Stream worsening oxygenation, purulent
tract infections
Infection positive blood secretions
(at least 48 h
(specimen containing at +
after
least one matching organism New/progressive radiographic
intubation)
to the blood specimen) infiltrate (if available)
Excluded organisms: “Normal respiratory flora,” “normal oral flora,” “mixed respiratory flora,” and,
unless identified from lung tissue or pleural fluid (with specimen obtained during thoracentesis or
initial placement of chest tube and NOT from an indwelling chest tube), Candida spp, coagulase-
negative staphylococci, Enterococcus spp.
Catheter- urine culture ≥105 CFU/mL
associated N.B., if urinary catheter in
Urinary Tract place for more than 5 days,
Infection. the catheter is removed, a
(at least 48 h new catheter is repositioned
after and a second specimen is
indwelling collected.
urinary secondary Blood Stream
catheter Infection (positive blood
positioning.) specimen containing at least
one eligible matching
organism to the urine
specimen)
Excluded organisms: “mixed flora,” Candida spp, yeast, mold, dimorphic fungi, parasites

Resistant Organisms
Guideline
Acinetobacter baumannii
Table 9: Recommended treatment options for infections due to Carbapenem-Resistant

Acinetobacter baumannii.(CRAB) (7),(13),(14),(15),(16),(17),(18)
• Resistance to at least anyone carbapenem (meropenem or imipenem).(18)
• Combination therapy with at least two active agents, is recommended for the treatment of CRAB
infections, even if a single agent demonstrates activity, at least until clinical improvement is
observed, because of the limited clinical data supporting any single antibiotic agent. (17)
• In situations when prolonged durations of therapy may be needed (e.g., osteomyelitis), step-down
therapy to a single active agent can be considered.(17)
Clinical Syndrome Recommended Treatment Alternative Treatment

• Colistin + Meropenem +
Ampicillin/sulbactam (even if non-
susceptible) (9),(17),(18)
• Colistin + (Imipenem/cilastatin or
Meropenem) Colistin + Tigecycline +
• Consider concomitant administration Ampicillin/Sulbactam
Pneumonia of inhaled Colistin when it is used
intravenously for VAP (5),(16),
however IDSA does not suggest the
use of nebulized antibiotics as
adjunctive therapy for CRAB
pneumonia, due to the lack of benefit
observed in clinical trials.(17),(18)
• Colistin + Meropenem +
Ampicillin/sulbactam.
(for critically ill patients if the Colistin + (Tigecycline OR
Bloodstream
local rate of MDR/carbapenem Ampicillin/ Sulbactam)
resistance > 10-15%).
Infections
• Colistin + (Imipenem/cilastatin or
Meropenem).
Complicated UTI As bloodstream infection

Enterobacteriaceae
Resistant Enterobacterales
Table 10: ESBL & AmpC β-Lactamase

The resistance
1-ESBL 2-AmpC β-Lactamase
gene/enzyme
Definition (7),(17) • Extended-spectrum • Transferable beta-lactam resistance, AMP-C
beta-lactamases
(ESBL)– transferable
resistance to 3rd and
4th generation
cephalosporins.

Resistant Organisms
Guideline
• ESBLs are enzymes
that inactivate most
Penicillins,
Cephalosporins, and
Aztreonam.
• EBSL-E generally
remains susceptible
to Carbapenems.
• Organisms carrying
ESBL genes often
harbor additional
genes or mutations in
genes that mediate
resistance to a broad
range of antibiotics.
The most Any gram-negative (Most recovered organisms) (less commonly
common organism has the recovered
Enterobacterales potential to harbor • Enterobacter cloacae organisms)
at risk for ESBL genes; however, complex
producing the they are most prevalent • Klebsiella aerogenes. • S. marcescens,
resistance in: • Citrobacter freundii • M. morgannii.
enzyme/gene (17) • Escherichia coli • Providencia
• Klebsiella spp
pneumoniae
• Klebsiella oxytoca
• Proteus mirabilis.
The antibiotics • Piperacillin- • First-generation • Ceftriaxone
avoided tazobactam is not Cephalosporins, Cefoxitin, (for infections
empirically (or suggested for the Cefotetan with limited
even if an isolate treatment of • Ceftriaxone, Cefotaxime, source control
initially tests infections outside of Ceftazidime (for any (e.g.,
susceptible to the urinary tract infection other than endocarditis,
these agents) (17) caused by ESBL-E uncomplicated cystitis) central
• Ceftriaxone, • Aminopenicillins (i.e., nervous
cefepime, cefoxitin amoxicillin, ampicillin). system
or cefotetan • Piperacillin-tazobactam is infections)
• N.B., if cefepime or not suggested for the
piperacillin- treatment of serious
tazobactam were infections caused by the
initiated as empiric mentioned organism.
therapy for • Aztreonam
uncomplicated
cystitis caused by an
ESBL-E and clinical
improvement
occurs, no change or
extension of
antibiotic therapy is
necessary.

Resistant Organisms
Guideline
The active • Carbapenems • TMP-SMX, • Cefepime (for
antimicrobial • Ciprofloxacin Fluoroquinolones, infections with
agents (17) • Levofloxacin Aminoglycosides, limited source
Tetracyclines
• Trimethoprim- control (e.g.,
sulfamethoxazole • Ceftriaxone, Ceftazidime endocarditis,
[TMP-SMX] & Piperacillin-tazobactam central
(used only if the
• Gentamicin nervous
mentioned organisms are system
• Piperacillin/tazobact
recovered in clinical urine infections)
am (only for UTI)
cultures in uncomplicated
cystitis.)
Table 11: CRE
The CRE
resistance
gene/
enzyme
• CREs are members of the Enterobacterales resistant to at least one Carbapenem
antibiotic or producing a carbapenemase enzyme. (17)
• Carbapenemase-producing Enterobacterales (formerly known as Carbapenemase
producing Enterobacteriaceae), an emerging resistance of concern (7)
• Carbapenamases enzymes, belong to Ambler class A, B or D beta-lactamases. (19)
• Carbapenem resistant Enterobacterales: These include the serine b-lactamases
Definition Klebsiella pneumoniae carbapenemase (KPC) (Ambler class A), metallo-b-
lactamase (MBL) including New Delhi MBL (NDM) or Verona integron-encoded
MBL (VIM), imipenemase (IMP) (Ambler class B) and OXA-48-like
carbapenemases (Ambler class D). (5), (19)
• KPCs hydrolyse penicillins, cephalosporins, monobactams and carbapenems.
• KPC, NDM and OXA-48 enzymes are among the carbapenem resistance
mechanisms of greatest concern. (5),(19)
• The drugs of choice for treatment of CRE: Tigecycline, Aminoglycosides and
Colistin however, IDSA guidelines don`t suggest Colistin for the treatment of
infections caused by CRE but consider it as an alternative agent for uncomplicated CRE
cystitis. (1),(17)
• Infections caused by Enterobacterales isolates without carbapenemase production
that remain susceptible to Meropenem and Imipenem (i.e., MICs ≤1 µg/mL) but
are not susceptible to Ertapenem (i.e., MICs ≥1 µg/mL) → the use of extended-
infusion Meropenem (or Imipenem - cilastatin) is suggested. (17)
Notes • Standard-infusion Meropenem or Imipenem-cilastatin may be reasonable for
uncomplicated cystitis. (17)
• For isolates susceptible to Meropenem but not susceptible to Imipenem (and vice versa),
in the absence of data to inform the optimal treatment approach, the treatment decision will
depend on the severity of illness of the patient and site of infection. For example, in this
scenario, Meropenem may be a reasonable treatment for a urinary tract infection but not
for a complex intra-abdominal infection. (17)
• For patients with CRE infections who within the previous 12 months have received medical
care in countries with a relatively high prevalence of metallo-β-lactamase-producing
organisms or who have previously had a clinical or surveillance culture where a metallo-

Resistant Organisms
Guideline
β-lactamase producing isolate was identified, preferred treatment options include the
combination of Ceftazidime-avibactam plus Aztreonam. (17)
• Since these organisms are mainly found in the intestine, any environmental surfaces that
come into contact with faecal material can become contaminated and serve as a reservoir
for cross-infection. In addition, these organisms generally prefer a wet environment, and
can quickly colonise sink drains and taps. They have also been known to contaminate
diluted disinfectants and detergent solutions used for cleaning. (17)
• The primary mode of cross-transmission is via the unwashed hands of clinical staff. (13)
Patients may also spread infection by touching their own urinary catheter or wound
drainage tube. (17)
Carbapenemases/ β-Lactamases (20)
Serine- β-Lactamases Metallo- β-Lactamases
Class A: KPC, IMI, SME, CTX-M
Class C: AmpC, ACT, CMY, DHA Class B: NDM, VIM, IMP
Class D: OXA-48
KPC OXA-48 NDM Other
Metallo
Metallo-beta-
New Delhi lactamases
metallob-lactamase (MBL) –
similar to
ESBL, but
can also
Definition include
resistance to
carbapenems,
mostly found
in
Pseudomonas
aeruginosa (2)
One of the following • Tigecycline (only • Combinati
for infections not on of
• Ceftazidime-avibactam involving the ceftazidi
• Tigecycline (only for infections not bloodstream or me-
involving the bloodstream or urinary tract) urinary tract) avibactam
• Although plus
aztreonam is aztreona
active against m
The active NDMs, it can be
antibiotics hydrolyzed by
against ESBLs, AmpC β-
CRE (17) lactamases,
KPCs, or OXA-
48-like
carbapenemases
which are
frequently co-
produced by
NDM-producing
isolate.
Resistant Organisms
Guideline
Table 12: Recommended treatment options for Carbapenem-Resistant Enterobacterales
(CRE) when Carbapenemase testing result is not available (7),(13),(17),(18),(20),(21)
(Treatment based on clinical syndrome plus risk factors for infection by MDR strains)
Empiric treatment is recommended when there are signs of infections with strong or multiple
risk factors for infection by MDR strains producing KPC or OXA-48 as follows: (21)
If there is one of the following:
• Known colonization or prior infection (or roommate infected) by Enterobacteriaceae strain
producing KPC or OXA-48
• Local epidemiology (or recent hospitalization in settings) with more than 20-25% prevalence of
carbapenem producing and ESBL- producing Enterobacteriaceae.
Plus, any of the following:
• Prior use of carbapenems and/or colistin.
• ICU admission or long admission in hospital wards.
• Severe hospital acquired infection.
• Immunosuppression, multiple comorbidities.
Clinical Recommended Alternative
Notes
Syndrome Treatment Treatment
Bloodstream • Colistin+ (Tigecycline • Monotherapy with
Infections (BSI) or Meropenem) ceftazidime/ avibactam
should be reserved in non-
N.B., For complicated life-threatening infections.
infections or (21)
hemodynamically • Colistin as a single agent
unstable patients, it is (for uncomplicated
recommended to use infections like UTI, any
Colistin Plus another other infection for which
agent to which source reduction has been
organism has done and patient is
demonstrated hemodynamically stable).
susceptible MIC (like (18)
tigecycline,
• Aminoglycosides (for
aminoglycosides) or
uncomplicated infections
high dose carbapenems
like UTI, any other
if MIC < 16).(18)
infection for which source
reduction has been done).
(18)
Uncomplicated • Nitrofurantoin, • A single dose of • The term complicated
Cystitis • Trimethoprim- an urinary tract infection
sulfamethoxazole Aminoglycoside (cUTI) refers to UTIs
(TMP-SMX) • Oral occurring in association
• Ciprofloxacin, or Fosfomycin (for with a structural or
Levofloxacin (their use E. coli only) functional abnormality of
for uncomplicated • Colistin, the genitourinary tract, or
cystitis is discouraged • Ceftazidime- any UTI in an adolescent or
when other safe and avibactam adult male.
effective options are
available) (17)

Resistant Organisms
Guideline
Complicated According to • cUTI is treated with similar
susceptibility: agents and for similar
Urinary Tract treatment durations as
• Levofloxacin (17) pyelonephritis.
Infections • Ciprofloxacin (17) • For cUTI where the source
• Ceftazidime/avibactam has been controlled (e.g.,
• Gentamicin or removal of a Foley
Amikacin catheter) and ongoing
concerns for urinary stasis
or indwelling urinary
hardware are no longer
present, it is reasonable to
select antibiotic agents and
treatment durations similar
to those that would be
selected for uncomplicated
cystitis. (17)
• If an antibiotic not active
against the causative
organism was administered
empirically for
uncomplicated cystitis, but
clinical improvement
occurred, it is generally not
necessary to repeat a urine
culture, change the
antibiotic regimen, or
extend the planned
treatment course. (17)
Complicated • Ceftazidime/avibactam • Tigecycline (approved for

Intraabdominal + Metronidazole intra-abdominal infection
Infections • Colistin + Tigecycline and skin–soft tissue
or Meropenem infection)- DO NOT use for
blood stream infection or
pneumonia as a
(18)
monotherapy.
Table 13: Recommended treatment options for Carbapenem-Resistant Enterobacterales (CRE)

(7), (13),(16),(17)
If Carbapenemase testing result is unavailable (treatment based on Lab report and clinical
syndrome)
It is suspected when there is resistance to at least anyone carbapenem (ertapenem, imipenem or
meropenem). (18)
Lab reports/Clinical Recommended Treatment Alternative Treatment
Syndrome

Resistant Organisms
Guideline
The following types of • Nitrofurantoin • Aminoglycosides a single
bacteria have higher risk to • TMP-SMX IV dose
harbor AmpC β- • Ciprofloxacin or
Lactamase: Levofloxacin
• Enterobacter cloacae
complex
• Klebsiella aerogenes.
• Citrobacter freundii
• S. marcescens,
• M. morgannii.
• Providencia spp
Uncomplicated AmpC-E
cystitis (17)
The following types of • Fluoroquinolones
bacteria have higher risk to • Oral step-down therapy with
harbor AmpC β- TMP-SMX or fluoroquinolones
Lactamase: have been shown to be
• Enterobacter cloacae reasonable treatment
complex considerations for
• Klebsiella aerogenes. Enterobacterales bloodstream
• Citrobacter freundii infections.
• S. marcescens,
• M. morgannii.
• Providencia spp
Invasive infections (17)
If resistance to aztreonam, • Meropenem • Ceftazidime- avibactam
ceftriaxone, cefotaxime, • Imipenem cilastatin • Ceftolozane-tazobactam
cefepime but susceptible to • Ertapenem
carbapenems, so it is likely
to be Extended-Spectrum B- ➢ N.B., it is suggested that the use
lactamase-producing of Meropenem or Imipenem-
Enterobacterales (ESBL-E) cilastatin, rather than Ertapenem,
ESBL producer Causing is preferred as initial therapy in
infections outside the critically ill patients with ESBL-
urinary tract (5), (13),(15),(17) E infections. (17)
Oral step-down therapy to
ciprofloxacin, levofloxacin, or
trimethoprim/sulfamethoxazole can
be considered after: (5),(15),(17)
1. Susceptibility to the oral agent is
demonstrated.
2. Patients are afebrile and
haemodynamically stable.
3. Appropriate source control is
achieved.
4. There are no issues with
intestinal absorption.

Resistant Organisms
Guideline
• Uncomplicated cystitis • Nitrofurantoin • Amoxicillin/clavulanate
due to extended- • Trimethoprim/
spectrum b-lactamase- sulfamethoxazole (if current isolates, or if using
producing empirically, recent isolates, are
Enterobacterales (ESBL- • Piperacillin/tazobactam fully susceptible.) (22)
E) (5),(13) Ciprofloxacin, levofloxacin, and
Carbapenems (17)
N.B., ESBL-E lab report
interpretation was mentioned before.
• Pyelonephritis or • Ciprofloxacin • Ertapenem

Complicated urinary • Levofloxacin • Meropenem
tract infection UTI due • Trimethoprim/sulfamethoxazole • Imipenem/Cilastatin
to extended-spectrum b- • Aminoglycosides for a full
lactamase-producing treatment course
Enterobacterales (ESBL-
E) (5),(13)
N.B., ESBL-E lab report
interpretation was mentioned before.
• If resistance to • Ceftazidime- avibactam (13),(18)

Aztreonam, Ceftriaxone, • Combination of Colistin,
Cefotaxime, Cefepime, Tigecycline, Aminoglycosides.
Meropenem or Imipenem • (Colistin or Aminoglycoside) +
or both but susceptible to (Carbapenem and/or
Ceftazidime avibactam, tigecycline)
so it is likely • Consider concomitant
Carbapenemase- administration of inhaled
Resistant Colistin /Aminoglycoside when
Enterobacterales (CRE) they are used intravenously for
Klebsiella pneumoniae VAP
carbapenemase (KPC)
producer (5),(13)
• If resistance to • Ceftazidime- avibactam + • Colistin plus other agent to

Aztreonam, Aztreonam (The two drugs which organism has
Ceftriaxone, should be infused demonstrated susceptible
Cefotaxime, Cefepime, concomitantly) MIC (like tigecycline,
Meropenem or aminoglycosides) or high
Imipenem or both, N.B., if a patient is infected with a dose carbapenems if MIC <
Ceftazidime- avibactam, CRE strain with an unknown 16. (18)
Flouroquinolones, carbapenemase status and the patient • Tigecycline (approved for
Aminoglycosides and has recently travelled from an area intra-abdominal infection and
Sulfamethoxazole where metallo-b-lactamases are skin –soft tissue infection)-
trimethoprim, it is likely endemic (e.g. Middle East, South DO-NOT use for blood
metallo-carbapenemase Asia, Mediterranean), treatment with stream infection or
producer (ie. (NDM), ceftazidime/avibactam plus pneumonia as a single agent.
(18)
(VIM) or, (IMP)) (5),(13) aztreonam is recommended.
uncomplicated infections like
UTI, any other infection for
which source reduction has
been done). (18)

Resistant Organisms
Guideline
• Carbapenem-resistant • Colistin + high dose
Enterobacterales with: carbapenem ± Tigecyclin
(5),(13) • Aminoglycoside + high dose
carbapenem ± Tigecyclin.
• Resistant to
Avibactam
OR
• Absence of new
options
Table 14: Recommended treatment options for Carbapenem-Resistant Enterobacterales (CRE)

(7),(13) (16),(17)
,
If Carbapenemase testing result is available
Lab reports/Clinical Recommended Treatment Alternative Treatment
Syndrome
Uncomplicated AmpC-E • Nitrofurantoin • Aminoglycosides A
cystitis (17) • TMP-SMX single IV dose
• Ciprofloxacin or
Levofloxacin
AmpC β-Lactamase • Fluoroquinolones

Invasive infections (17) • Oral step-down therapy with
TMP-SMX or fluoroquinolones
have been shown to be reasonable
treatment considerations for
Enterobacterales bloodstream
infections
Extended-Spectrum B- • Meropenem • Ceftazidime- avibactam
lactamase-producing • Imipenem cilastatin • Ceftolozane-tazobactam
Enterobacterales (ESBL-E) • Ertapenem
ESBL producer Causing
infections outside the ➢ N.B., it is suggested that the use of
urinary tract (5),(13),(15),(17) Meropenem or Imipenem-
cilastatin, rather than Ertapenem, is
preferred as initial therapy in
critically ill patients with ESBL-E
infections. (17)
Oral step-down therapy to

ciprofloxacin, levofloxacin, or
trimethoprim/sulfamethoxazole can
be considered after: (15),(17)
• Susceptibility to the oral agent is

demonstrated.
• Patients are afebrile and
haemodynamically stable.

Resistant Organisms
Guideline
• Appropriate source control is
achieved.
• There are no issues with intestinal
absorption.
Uncomplicated cystitis due • Nitrofurantoin • Amoxicillin/clavulanate

to extended-spectrum b- • Trimethoprim/ sulfamethoxazole • (if current isolates, or if
lactamase-producing • Piperacillin/tazobactam using empirically, recent
Enterobacterales (ESBL-E) isolates, are fully
(5), (13)
susceptible.) (22)
• Ciprofloxacin,
levofloxacin, and
(17)
Carbapenems
Pyelonephritis or • Ciprofloxacin • Ertapenem.
Complicated urinary tract • Levofloxacin • Meropenem.
infection UTI due to • Trimethoprim/ sulfamethoxazole • Imipenem/Cilastatin.
extended-spectrum b- • Aminoglycosides for a
lactamase-producing full treatment course.
Enterobacterales (ESBL-E)
(5),(13)
Carbapenemase-Resistant • Ceftazidime- avibactam (13),(18) • Meropenem+Ertapenem

Enterobacterales (CRE) • Combination of Colistin, (25)
Klebsiella pneumoniae Tigecycline, Aminoglycosides. use ertapenem infusion
carbapenemase (KPC) • (Colistin or Aminoglycoside) + prior to a high-dose
producer (5),(13) (Carbapenem and/or tigecycline) meropenem infusion as a
salvage therapy for
• Consider concomitant critically ill patients with
administration of inhaled Colistin CRE infections.
/Aminoglycoside when they are • Meropenem+
used intravenously for VAP Ertapenem+
(Colistin/Tigecycline)
(25)
It might be a reasonable
strategy for severe CRE
infections.
Metallo-carbapenemase • Ceftazidime- avibactam + • Colistin Plus other agent
producer (ie. (NDM), Aztreonam (The two drugs should to which organism has
(VIM) or, (IMP)) (5),(13) be infused concomitantly) demonstrated susceptible
MIC (like tigecycline,
N.B., if a patient is infected with a aminoglycosides) or high
CRE strain with an unknown dose carbapenems if MIC
carbapenemase status and the patient < 16. (18)
has recently travelled from an area • Tigecycline (approved for
where metallo-b-lactamases are intra-abdominal infection
endemic (e.g. Middle East, South Asia, and skin –soft tissue
Mediterranean), treatment with infection)- DO-NOT use
ceftazidime/avibactam plus aztreonam for blood stream infection
or pneumonia as a single
is recommended.
agent. (18)
uncomplicated infections

Resistant Organisms
Guideline
like UTI, any other
infection for which source
reduction has been done).
(18)
• Meropenem+ Ertapenem
(26)
N.B., the synergistic

activity of meropenem
plus ertapenem
combination suggests
this combination can be a
possible way to treat the
infection caused by the
carbapenem-resistant
organisms, especially for
IMP or NDM producer
with a lesser minimum
inhibitory
concentration (MIC) and
the infected individual
who was not
recommended to
use colistin or tigecycline.

Resistant Organisms
Guideline
Pseudomonas aeruginosa
Table 15: Recommended treatment options for infections due to Pseudomonas aeruginosa (PA)
and
Difficult-to-Treat P.aeruginosa (DTR-PA).
Definitions • Pseudomonas aeruginosa is a key gram-negative aerobic bacillus in the
differential diagnosis of several infections. This organism is important because
it is often antibiotic resistant and can cause severe hospital-acquired infections
associated with a high mortality rate, especially in immunocompromised hosts.
(23)
P. aeruginosa is intrinsically resistant to numerous antibiotics and can
acquire resistance to other agents during therapy. Some strains are multidrug
resistant (i.e, they are resistant to three or more classes of antibiotics). (23)
• MDR- P. aeruginosa is defined as P. aeruginosa not susceptible to at least one
antibiotic in at least three antibiotic classes for which P. aeruginosa susceptibility
is generally expected: penicillins, cephalosporins, fluoroquinolones,
aminoglycosides, and carbapenems. (17)
• In 2018, the concept of “difficult-to-treat” resistance was proposed which is
defined as P. aeruginosa exhibiting non-susceptibility to all the following:
piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, meropenem,
imipenem-cilastatin, ciprofloxacin, and levofloxacin. (17)
• Carbapenem resistant PA (CRPA): Resistance to at least anyone carbapenem
(meropenem or imipenem). (18)
Clinical
Recommended Treatment
Syndrome
• When P. aeruginosa isolates test susceptible to both no carbapenem β-lactam
agents (i.e., piperacillin tazobactam, ceftazidime, cefepime, aztreonam) and
Any clinical carbapenems, the no carbapenem β-lactam agents are preferred over carbapenem
syndrome therapy. (17)
due
• If the isolate remains susceptible to a traditional non-carbapenem β-lactam (e.g.,
Pseudomonas
aeruginosa cefepime) on repeat testing, it is recommended to administer the non-carbapenem
(17) agent as high-dose extended infusion therapy (e.g., cefepime 2 g IV every 8
hours, infused over at least 3 hours) (17)
Use one of the following antibiotics:

• Piperacillin/tazobactam
• Ceftazidime
Any clinical • Cefepime
syndrome • Ciprofloxacin
due to CRPA • Levofloxacin
susceptible to • Amikacin (only if urinary tract infection)
other • When P. aeruginosa isolates not susceptible to any carbapenem agent but
antimicrobial susceptible to traditional βlactams, the administration of a traditional agent as
agents (7), (13), high-dose extended-infusion therapy is suggested, and repeat AST is encouraged.
(17), (20), (22)
(17)
• For critically ill patients or those with poor source control with P. aeruginosa
isolates resistant to carbapenems but susceptible to traditional βlactams, use of a
novel β-lactam agent that tests susceptible (e.g., ceftolozane-tazobactam &
ceftazidime-avibactam) is a reasonable treatment approach.

Resistant Organisms
Guideline
• Combination of two agents from different classes with in vitro activity against P.
aeruginosa for empiric treatment of serious infections known or suspected to be
caused by P. aeruginosa in the following conditions: (22), (23)
1. When signs of severe sepsis or septic shock are present
2. Neutropenic patients with bacteremia
3. Burn patients (who have a high incidence of multidrug-resistant P.
aeruginosa infections) with serious infections.
4. In other settings where the incidence of resistance to the chosen antibiotic
class is high (e.g., >10 to 15 %)
For patients with severe infections caused by CRPA susceptible in vitro only to
Colistin or aminoglycosides a combination therapy is suggested. Colistin plus other
agent to which organism has demonstrated susceptible MIC or in intermediate range
or SDD (susceptible dose dependent) can be used. (18)
Any clinical • Ceftolozane/tazobactam (preferred empirical choice in absence of concomitant
syndrome risk of CRE)
due to DTR- • Ceftazidime/avibactam
PA (5), (13), • Colistin + (Imipenem/cilastatin OR Meropenem)
(15),(16), • Combination of Colistin, Tigecycline, Aminoglycosides. (16)
(17),(22) • (Colistin or Aminoglycoside) + (Carbapenem and/or tigecycline) (16)
• If resistant to Ceftazidime/avibactam:
o Ceftazidime/ avibactam + Aztreonam (5)
o Colistin + (Imipenem/cilastatin OR Meropenem)
o Aminoglycosides + carbapenems
• Consider concomitant administration of inhaled Colistin /Aminoglycoside when
they are used intravenously for VAP (7), however IDSA guidelines does not
suggest the use of nebulized antibiotics for the treatment of respiratory infections
caused by DTR-P. aeruginosa. (17)
• Combination antibiotic therapy is not suggested if susceptibility to ceftolozane-
tazobactam, ceftazidime-avibactam, has been confirmed (17)
N.B. oral Fosfomycin for DTR-P. aeruginosa cystitis is not recommended as it is
associated with a high likelihood of clinical failure (17)

Resistant Organisms
Guideline
Figure 1: Clinical approach to patients with suspected P. aeruginosa infection (24)
Figure 2: Suggested algorithm for the treatment of MDR Gram-negative bacterial

infections admitted to hospitals. (22)

Resistant Organisms
Guideline
Stenotrophomonas maltophilia
Table 16: Recommended treatment options for infections due to Stenotrophomonas

maltophilia (13), (17)
• Stenotrophomonas maltophilia is an aerobic, glucose non-fermenting, gram-negative bacillus that is
ubiquitous in water environments.
• The organism has a long history of changing nomenclatures and a complicated phylogeny.
• Although generally believed to be less pathogenic than many other nosocomial organisms, S.
maltophilia produces biofilm and virulence factors that can enable colonization or infection in
vulnerable hosts, such as those with underlying lung disease and hematological malignancies.
• S. maltophilia is often recovered as a component of a polymicrobial infection further challenging
the need for targeted S. maltophilia therapy.
• It is not recommended to use Polymyxins for the treatment of S. maltophilia infections.
Clinical Syndrome Recommended Treatment Notes
Any clinical syndrome cause by S. • Two of the following agents: Tigecycline: FDA cites
maltophilia TMP-SMX (The preferred higher risk of death
agent), Tigecycline, or among patients given
Levofloxacin. tigecycline compared to
N.B., A general concern with other antibacterials and
tetracycline derivatives is that recommends use only in
they achieve rapid tissue situations where
distribution following
alternative therapy is not
administration, resulting in (13)
limited concentrations in the suitable.
urine and poor serum
concentrations.
• When significant clinical
instability is evident or
intolerance to or inactivity of
other agents: Ceftazidime-
avibactam + Aztreonam,
• For mild and polymicrobial
infection where the role of S.
maltophilia is unclear, use
monotherapy of monotherapy
of TMP-SMX, Levofloxacin,
Tigecycline. (13)
Multi-resistant Gram-positive cocci
Vancomycin-resistant Enterococci (VRE)
Table 17: Recommended treatment options for Vancomycin-resistant Enterococci (VRE). (7)
Clinical Syndrome Recommended Treatment
Pneumonia Linezolid
Bloodstream infections Linezolid OR (Daptomycin +/- Carbapenem)
Complicated intraabdominal infections Linezolid OR Tigecycline
Complicated urinary tract infections Linezolid OR Daptomycin

Resistant Organisms
Guideline
Suggested dosing of antibiotics for the treatment of infections caused by antimicrobial resistant
organism
Table18: Suggested dosing of antibiotics for the treatment of infections caused by antimicrobial
resistant organism (13), (17),(18),(20))
Agent Adult dose Target Organism
(Assuming normal renal and liver function)
Amikacin Uncomplicated cystitis: 15 mg/kg IV as a ESBL-E, AmpC-E,
single dose CRE, DTR-P.
Any clinical syndrome due to CRPA susceptible aeruginosa
to other antimicrobial agents: 15mg/kg
All other infections: 20 mg/kg IV once;
subsequent doses and dosing interval based on
pharmacokinetic evaluation.
N.B., Use adjusted body weight for patients
.120% of ideal body weight for aminoglycoside
dosing.
Ampicillin/sulbactam Total daily dose of 6-9 grams of sulbactam CRAB
N.B., (high dose of ampicillin/ sulbactam used
but no agreed consensus on the right dose)
Potential infusion strategies include the
following:
- 9 grams of ampicillin-sulbactam (6 grams’
ampicillin, 3 grams sulbactam) IV every 8
hours, infused over 4 hours
- 27 grams of ampicillin-sulbactam (18 grams’
ampicillin, 9 grams sulbactam) IV as a
continuous infusion
For mild infections caused by CRAB isolates
susceptible to ampicillin-sulbactam, particularly
if intolerance or toxicities preclude the use of
higher dosages.
- 3 grams of ampicillin-sulbactam (2 grams
ampicillin, 1-gram sulbactam) IV every 4
hours, infused over 30 minutes
Aztreonam 2g IV over 3 h /6h DTR-PA
Cefepime Uncomplicated cystitis: 1gram IV every 8 AmpC-E, CRPA
hours, infused over 30 minutes All other
infections: 2 grams IV every 8 hours, infused
over 3 hours (if possible)
Ceftazidime
Any clinical syndrome due to CRPA susceptible CRPA
to other antimicrobial agents: 2 g IV q8h
Ceftazidime/avibactam 2.5 grams IV every 8 hours, infused over 3 CRE, DTR-P.
hours aeruginosa
Ceftazidime/avibactam Metallo-β-lactamase-
Ceftazidime-avibactam: 2.5 grams IV every 8
PLUS Aztreonam producing CRE, S.
hours, infused over 3 hours.
maltophilia

Resistant Organisms
Guideline
PLUS
Aztreonam: 2 grams IV every 6-8 hours (every
6-hour dosing preferred if possible), infused
over 3 hours.
Administered at the same time as ceftazidime-
avibactam
Ceftolozane/tazobactam Cystitis: 1.5 grams IV every 8 hours, infused DTR-P. aeruginosa
ESBL-E (outside
over 1 hour
theUTI)
All other infections: 3 grams IV every 8 hours,
infused over 3 hours
Ciprofloxacin ESBL-E, AmpC-E,
Cystitis: 400 mg IV every 12 hours or 500 mg
CRPA
PO every 12 hours
All other infections: 400 mg IV every 8 hours
OR 750 mg PO every 12 hours
Colistin (14) CRE,
Colistin IV 2.5 mg Colistin Base Activity
DTR-P. aeruginosa,
(CBA)/kg IV loading dose, then 1.5 mg CBA
CRAB
over 1 hour IV /12 h
(14)
Colistin inhalation Colistin inhalation 75 to 150 mg CBA twice
daily.
Daptomycin VRE
IV 8-12mg/kg/day
Ertapenem ESBL-E, AmpC-E
1 gram IV every 24 hours, infused over 30
minutes
CRE
Fosfomycin Uncomplicated cystitis: 3 grams PO as a single ESBL-E. coli cystitis
dose
Gentamicin Uncomplicated cystitis: 5 mg/kg/dose IV as a ESBL-E, AmpC-E,
CRE, DTR-
single dose
P.aeruginosa
All other infections: 7 mg/kg IV once;
subsequent doses and dosing interval based on
pharmacokinetic evaluation.
N.B., Use adjusted body weight for patients (120% of
ideal body weight for aminoglycoside dosing).
Imipenem-cilastatin Uncomplicated cystitis (standard infusion): ESBL-E, AmpC-E,
500 mg IV every 6 hours, infused over 30 CRE, CRAB, DTR-
minutes. PA
All other ESBL-E or AmpC-E infections: 500
mg IV every 6 hours, infused over 30 minutes.
All other CRE and CRAB infections: 500 mg IV
every 6 hours, infused over 3 hours
Levofloxacin 750 mg IV/PO every 24 hours. ESBL-E, AmpC-E,
S. maltophilia,
CRPA
Resistant Organisms
Guideline
Linezolid 600 mg IV every 12 hours. VRE
Metronidazole Complicated intraabdominal infections: 500 mg
/ 6h
Meropenem Uncomplicated cystitis (standard infusion): 1 ESBL-E, AmpC-E,
grams IV every 8 hours, infused over 30 CRE, CRAB, DTR-
minutes. PA
All other ESBL-E or AmpC-E infections: 1–2 g
IV q8h, infused over 30 minutes.
All other CRE and CRAB infections: 2 g IV
every 8 hours, infused over 3 hours
Nitrofurantoin Macrocrystal/monohydrate: 100 mg PO every ESBL-E cystitis,
12 hours. AmpC-E cystitis
Piperacillin-tazobactam Any clinical syndrome due to CRPA susceptible
to other antimicrobial agents: 4.5 g IV loading
over 30 minutes then, 4 hrs later, start 4.5gmIV over
4 hours and then repeat every 8 hours over 4 hours.
Tigecycline 200 mg IV as a single dose, then 100 mg IV CRE, CRAB, S.
every 12 hours maltophilia
Trimethoprim - Cystitis: 160 mg (trimethoprim component) PO ESBL-E, AmpC-E,
sulfamethoxazole q12hOther infections: 8–12 mg/kg/day S. maltophilia
(trimethoprim component) PO divided every 8–
12 hours (consider maximum dose of 960 mg
trimethoprim component per day).
Duration of therapy for common clinical syndromes
Table 19: Duration of therapy for common clinical syndromes

Clinical syndrome Duration of therapy (7),(18)
Ventilator associated pneumonia or 7- 10 days
hospital acquired pneumonia
Complicated urinary tract 10 days
infections
Catheter associated UTI 5-7 days
Removal of catheter is strongly recommended if infection with
an MDR organism is confirmed
Intra-abdominal infections 5- 7 days
Central line associated blood 10-14 days
stream Removal of central line is strongly recommended if infection
Infections with an MDR organism is confirmed
BSI due to CRE 7-14 days (7)
Complicated Intraabdominal 5- 7 days (7)
Infections
Any clinical syndrome due to • 5-14 days (7)
CRPA susceptible to other • 5-10 days for complicated urinary tract infection and
antimicrobial agents complicated intra-abdominal infection. (7)
• A treatment course of 10-14 days is suggested for hospital-
acquired or ventilator-associated pneumonia and
bloodstream infection. (7)
Resistant Organisms
Guideline
Any clinical syndrome due to • 10-14 days (7)
DTR-PA
References
1- Parmanik A, Das S, et al. "Current treatment strategies against multidrug-resistant bacteria: a review." Current
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Resistant Organisms
Guideline
Contributors
Editorial board
Dr. Shimaa Nasr Eldeen (chief editor) Dr. Shimaa Sayed
Manager of Rational Drug Use Unit – Rapporteur Manager of Medication Management Unit- Drug
of the National Rational Antimicrobial Use Utilization and Pharmacy Practice General
Committee -Drug Utilization and Pharmacy Administration – EDA
Practice General Administration – EDA
Under the Supervision
Of
Dr. Shereen Abdel Gawad
Head of the Pharmaceutical Care Central Administration – Head of National Rational Antimicrobial Use
Committee-EDA.
&
Dr. Abeer El behairy
General Manager of Drug Utilization and Pharmacy Practice General Administration - Head of National
Antimicrobial Team – EDA
Members of the National Rational Antimicrobial Use Committee
(Ordered Alphabetically)
Dr. Ahmed Motawea Prof. Maha Abdel Aziz El-touny

Chief of medical supply dept. Prof. Internal Medicine ASU.
Armed Forces Medical Services Authority IPC consultant Ministry of Interior
Prof. Amin Abdelbaki Prof. Nirmeen Ahmed Sabry
Head of Hepatology, GIT and Infectious Diseases at Professor of clinical pharmacy- Cairo University
National Hepatology and Tropical Research Medication management consultant
Institute
Dr. Eman Nadim Dr. Sherif Kamal
Clinical pharmacist at the central administration for Consultant of the Egyptian Healthcare Authority
Unified Procurement Authority (EHA Representative)
(UPA Representative)
Dr. Heba Hossam Dr. Sally Mohy El deen
Quality and Patient Safety Consultant Director IPC General Directorate
(GAHAR Representative) (MOHP Representative)

Resistant Organisms

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Guideline

Central Administration of Pharmaceutical Care

General Administration For Drug Utilization &Pharmacy Practice

National Guidance for Antimicrobial Use in Infections with

National Rational Antimicrobial Use Committee

National Guidance for Antimicrobial Use in Infections with Multi-Drug

National Guidance for Antimicrobial Use in Infections with Multi-Drug

A. baumannii Acinetobacter. baumannii

The burden of antimicrobial resistance (AMR) on the global level

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Definitions of MDR, XDR and PDR for different MRGN

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Table 2: Susceptibility of Acinetobacter baumannii (8)

Table 3: Definition of MDR, XDR and PDR Enterobacteriaceae (8)

National Guidance for Antimicrobial Use in Infections with Multi-Drug

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Table 5: Definition of MDR, XDR and PDR Pseudomonas aeruginosa (8)

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Table 8: Diagnostic criteria for infections (11)

National Guidance for Antimicrobial Use in Infections with Multi-Drug

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Table 9: Recommended treatment options for infections due to Carbapenem-Resistant

Clinical Syndrome Recommended Treatment Alternative Treatment

Complicated UTI As bloodstream infection

Table 10: ESBL & AmpC β-Lactamase

National Guidance for Antimicrobial Use in Infections with Multi-Drug

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Table 11: CRE

National Guidance for Antimicrobial Use in Infections with Multi-Drug

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Complicated • Ceftazidime/avibactam • Tigecycline (approved for

Table 13: Recommended treatment options for Carbapenem-Resistant Enterobacterales (CRE)

National Guidance for Antimicrobial Use in Infections with Multi-Drug

National Guidance for Antimicrobial Use in Infections with Multi-Drug

• Pyelonephritis or • Ciprofloxacin • Ertapenem

• If resistance to • Ceftazidime- avibactam (13),(18)

• If resistance to • Ceftazidime- avibactam + • Colistin plus other agent to

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Table 14: Recommended treatment options for Carbapenem-Resistant Enterobacterales (CRE)

AmpC β-Lactamase • Fluoroquinolones

Oral step-down therapy to

• Susceptibility to the oral agent is

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Uncomplicated cystitis due • Nitrofurantoin • Amoxicillin/clavulanate

Carbapenemase-Resistant • Ceftazidime- avibactam (13),(18) • Meropenem+Ertapenem

National Guidance for Antimicrobial Use in Infections with Multi-Drug

N.B., the synergistic

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Use one of the following antibiotics:

National Guidance for Antimicrobial Use in Infections with Multi-Drug

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Figure 2: Suggested algorithm for the treatment of MDR Gram-negative bacterial

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Table 16: Recommended treatment options for infections due to Stenotrophomonas

Multi-resistant Gram-positive cocci

Vancomycin-resistant Enterococci (VRE)

National Guidance for Antimicrobial Use in Infections with Multi-Drug

National Guidance for Antimicrobial Use in Infections with Multi-Drug

Duration of therapy for common clinical syndromes