Brief review of treatment of nosocomial pneumonia, with emphasis on the problem of multi- drug resistant organisms

1. Treatment of Nosocomial PneumoniaTreatment of Nosocomial Pneumonia
(HAP, HCAP, VAP)(HAP, HCAP, VAP)
No Risk Factors for MDROs (Multi Drug Resistant Organisms)
Ceftriaxone + Azithromycin
1 – 2 gm IM or IV / 12 – 24h 500 mg / day
Or
Respiratory Fluoroquinolone (Not Ciprofloxacin)
Levofloxacin 750 mg/day
Moxifloxacin 400 mg/day
Or
Carbapenem
Imipenem/Cilastatin
Meropenem
Parenteral treatment is given for 7 Days and until vitally stable for >48hh.

2. Risk Factors for MDROs
• Initial empiric antibiotic treatment should include:
o Antipseudomonal agent:
- Antipseudomonal penicillin (Pipracillin/Tazobactan).
- Antipseudomonal cephalosporin (Ceftazidime or Cefepime).
- Carbapenem (Imipenem/Cilastatin or Meropenem).
In severe infection, 2 classes of anti-pseudomonal agents are used.
o Anti- MRSA agent (Vancomycin or Linezolid).
In severe infection, Vancomycin is started by a loading dose of
25 – 30 mg/Kg, then maintained at 15 – 20 mg/kg/ 8 – 12h.
• Aminoglycosides or colistin may be used as alternative choices in
patients with Gram –ve MDROs. They should be used for the shortest
possible course, with close monitoring of renal functions.
Dose adjustment may be required according to renal function.

3. Multi Drug Resistant Organisms (MDROs)Multi Drug Resistant Organisms (MDROs)
• They are microorganisms, predominantly bacteria, that are resistant
to one or more classes of antibacterial agents.
• Lack of a standardized definition limits comparison of resistance
data from different populations.
Hazards MDROs constitute one of the most serious and growing
threats to public healyh:
• ↑ hospital stay, cost and complications.
• Compulsory use of more toxic antibiotics → adverse effects, eg,
nephrotoxicity of aminoglycosides, colistin.
• ↑ Mortality
• Perpetuation of the problem of MDROs through:
o Colonization/infection of other patients or health care workers.
o Contamination of equipment, environmental surfaces.
o Transmission of resistant traits to other bacteria.

4. Increasing Prevalence of MRSA
MRSA was 1st
isolated in USA in 1968

5. • Introduction of a
resistant organism to a
potentially susceptible
population.
• Dissemination of
resistant organisms.
Potentially preventable by
Infection Control Program,
particularly isolation precautions.
• Selection of a resistant
subpopulation.
• Expression of dormant
resistance.
• Acquisition of resistance
by a previously
susceptible strain.
Potentially preventable by
Antibiotic Stewardship
Program.
The selection of resistance in one
organism in one part of the world,
even within an animal population,
may have long- term important
implications for human health
globally.
Mechanisms of Appearance and Spread of MDROs

6. Evidence that Organism Resistance is
Closely Related to Antibiotic Use
• Antimicrobial resistance is more common in nosocomial bacterial
strains than in community- acquired infections.
• Patients infected with resistant strains are more likely to have received
prior antibiotics.
• Hospital areas with highest rates of antimicrobial resistance have the
highest rates of antimicrobial use.
• Increasing duration of patient exposure to antimicrobials ↑ the
likelihood of colonization with resistant organisms.
Examples of Improper Antibiotic Use Favoring Development of MDROs
• Antibiotics for viral infection. (eg, upper respiratory infection)
• Antibiotics for specimen contamination. (eg, by skin flora)
• Antibiotics for asymptomatic colonization. ((eg, UTI)
• Improper antibiotic selection: overuse of broad spectrum agents /
or using non- clinically effective agents (even if effective in vitro).
• Improper antibiotic dose or duration.

7. Risk Factors for Acquisition of MDROs
• Recent IV antimicrobial therapy (last 3 months).
• Hospitalization for > 5 days.
• Attendance of an extended care facility.
• Maintenance haemodialysis.
• Home infusion therapy (including antibiotics).
• Home wound care.
• Family member with MDROs.
• Environmental colonization with MDROs (common in ICU).
• Immunocompromized state (cancer chemotherapy,
immunosuppressive treatment, HIV infection).
• Risk factors for MDROs-VAP:
o Septic shock before VAP.
o ARDS before VAP.
o Acute renal replacement therapy before VAP.

8. Combating Multi Drug Resistant OrganismsCombating Multi Drug Resistant Organisms
• It is recommended that all hospitals, large and small, with or without
perceived problems of bacterial resistance to antimicrobials, implement
a set of measures to reduce the burden and transmission of MDROs.
• All efforts in this respect generally fall under 2 basic strategic
programs: infection control and antibiotic stewardship.
• Such programs should be considered a shared responsibility of the
whole medical institution personnel from top administration down to
service workers.
• A dedicated program leader (physician – pharmacist) should be
assigned and authorized to manage a team work to achieve well defined
goals.
• Hospital committees particularly involved in these programs are
Infection Control Committee (ICC), Pharmacy and Therapeutics
Committee (PTC) and Morbidity Mortality Committee (MMC).
An Antibiotic Utilization Subcommittee may also be launched to set
local antibiotic guidelines and supervise antibiotic use.

9. Infection Control ProgramInfection Control Program
• Most of the health care delivery related factors are due to poor
adherence to recommended evidence based infection
prevention/control practices.
• Despite recognition that poor hand hygiene practice is a leading
cause of pathogen transmission, the existence of major national and
international guidelines, and initiatives to improve hand hygiene
practices among health care workers, compliance with recommended
hand hygiene practices among health care personnel remains
unacceptably low.
• The CDC Guidelines for Isolation Precautions in Hospitals
should be strictly applied, particularly concerning isolation of patients
colonized or infected with resistant organisms.
• It is recommended that hospitals choose organisms which are of
special clinical and epidemiologic importance to identify patients in
need for isolation.
• The validity of treatment of colonized patients is controversial, but
their isolation may be required exactly as infected patients.

10. Antibiotic Stewardship Program (ASP)Antibiotic Stewardship Program (ASP)
• It is a hospital- based program intended to track and
improve antibiotic use in order to improve their efficiency,
reduce their costs and adverse effects and, particularly,
reduce their potential to cause selection and spread of
MDROs.
• ASP includes not only limitation of the use of
inappropriate agents, but also the appropriate selection
and dosing of antimicrobial agents in order to achieve the
optimal efficiency in managing infections.
• It aims to have all patients treated with the most efficient,
least toxic and least costly antibiotic for the optimal
duration of time.

11. Role of Microbiologist
Restricted Reporting of Some Selected Broad Spectrum Antibiotics
• Sensitivity to some selected broad spectrum antibiotics might not be
released in the report, unless:
o resistance to narrower spectrum antibiotics documented
(eg, sensitivity to carbapenems released in case of resistance to
β-lactams).
o requested by an authorized physician.
• Advantage: more prudent, less costly antibiotic selection.
• Disadvantage: possibly ineffective treatment, resistance.
Selective Reporting of C/S (Culture and Sensitivity) results
Disc diffusion method
for Antibiotic Sensitivity

12. Restricted Reporting of Clinically Ineffective Antibiotics
even in Presence of Documented in-vitro Organism Susceptibility
Demonstration of in-vitro susceptibility of an isolate to a particular
antibiotic in the lab does not necessarily indicate clinical effectiveness
when this antibiotic is given to treat a clinical infectious disease.
Clinical resistance may result from:
• Low systemic bioavailability.
• Low penetration into the infection site → failure to achieve target MIC,
particularly if it is relatively high (intermediate resistance).
• Presence or retained pus or foreign body.
• Rapid development of resistant strains.
Examples of “in-vitro only” susceptibility that should not be reported:
- ESBL (extended spectrum β-lactamase producing) organisms should
not be reported sensitive to β-lactams.
- Oxacillin resistant Staph. aureus (MRSA) should not be reported
sensitive to β-lactam/β-lactamase inhibitors and carbepenems.

13. Inclusion of Useful Hints in the C/S Report
• Blood sample probably contaminated with skin flora.
• Sputum sample probably contaminated with mouth flora.
• Starting with an antibiotic combination recommended to prevent rapid
development of resistance.
Examples:
Recognition and Reporting of Antimicrobial Resistance Patterns
• Unusual antibiograms, especially multiply resistant patterns, can be
helpful for early identification of outbreak- related isolates.
• An even earlier indicator is a trend towards increasing resistance in
quantitative susceptibility tests (which are generally preferred to
simple break point systems):
o ↓ mean zone diameter around antibiotic discs.
o ↑ MIC.
• WHONET is a free web application supported by WHO that checks
quantitative susceptibility test results and alerts for unusual drug
resistance.

14. Role of Pharmacist
There are 4 possible general strategies to improve antibiotic
utilization in order to reduce the burden of MDROs:
• Use the proper.
• Do not use / modify the improper.
• Rotate.
• Combine.
Use the Proper Antibiotic
Antibiotic Selection Should Consider
• National guidelines.
• Local guidelines based on local microbial epidemiology, antimicrobial
susceptibility patterns and drugs available in hospital formulary.
Such guidelines should cove in particular the most commonly
encountered conditions as CAP, UTI, blood stream infection and
surgical prophylaxis.
• Expert advice from highly qualified consultants and infectious
disease specialists.
• Discussion of complex issues in dedicated committees as ICC, PTC,
MMC.

15. Pharmacist Role to Support Proper Antibiotic Selection
• Selection of antibiotics to be included or excluded from hospital
formulary. On light of clinical and microbiologic data, the most
effective and potentially least toxic antibiotics are to be included.
• Dispensing certain broad spectrum antibiotics is restricted unless
ordered by an authorized consultant or infectious disease specialist.
Do Not Use / Modify the Improper Antibiotic
Pharmacy Tracking
Pharmacy Driven InterventionsPharmacy Tracking
• Review of Medical Records: to ensure full documentation of
antibiotic prescription, including indication, dose and duration so that
antibiotic courses can be easily identified and tracked.
• Analysis of Antibiotic Utilization Trends: for both in- patients and
out- patients.
• Reporting issues of antibiotic use and misuse to the administration
and relevant staff.

16. Pharmacy Driven Interventions in collaboration with the treating
physician, microbiologist and infectious disease specialist:
• De- escalation of antibiotic therapy based on culture results and
clinical response.
• Conversion of open- ended antibiotic orders to automatic stop
orders, eg, in surgical prophylaxis.
• Shift from parenteral to oral therapy, eg, quinolones.
• Stop unnecessary antibiotics in patients diagnosed with
Clostridium difficile infection.
• Dose modification based on changes in renal / liver function and
other variables.

17. • Dose optimization, eg, extended infusion of β-lactams to improve
time- dependent killing.

18. Rotate Antibiotics
Combine Antibiotics
The validity of rotational or cyclic antibiotic use is controversial,
eg, rotating gentamycin with amikacin
Combination therapy may be recommended to prevent emergence of
resistance strains, particularly in conditions requiring prolonged
antibiotic courses. This is the basis for current treatment
recommendations for TB.
This approach may, however, ↑ costs and the potential for MDROs.

19. Other Components of ASP
Administration should be serious in provision of the required human,
financial and IT resources as well as authoritative privileges required.
IT (Information Technology) Presence of a computerized MIS (Medical
Information System) allows:
• Faster and more efficient communication between physicians,
pharmacists and microbiologists.
• Easier documentation and tracking of antibiotic prescriptions.
Health education Campaigns including fliers, multimedia and
awareness weeks:
• Targeting Physicians and Health Care Workers.
• Targeting Patients and Families:
o Use only antibiotics prescribed by health care professionals.
o Use antibiotics exactly as prescribed.
o Complete the treatment course, even if you feel better.