Dr. Jervin Mano, MD

The Hidden Epidemic

Epidemiology of nosocomial infections Pathogens involved in nosocomial infection Therapeutic guidelines De-escalation approach Prevention

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Definition Incidence Historical milestones Classification Risk factors Mode of transmission Pathologic agents Drugs used Rx of common NI Prevention

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Nosocomial infection comes from Greek words “nosus” meaning disease and “ komeion” meaning to take care of - disease contracted by a patient while under medical care.

Also called as HOSPITAL ACQUIRED INFECTION

Infections are considered nosocomial if they first appear 48hrs or more after hospital admission or within 30 days after discharge.

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The incidence of NI is estimated at 5-10% in tertiary care hospitals reaching up to 28% in ICU.

One-third of nosocomial infections are considered preventable.

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Nosocomial infections are responsible for about 100,000 deaths per year in hospitals

The patients must stay in the hospital 4-5 additional days.

More than 70% of bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used in treatment

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New cutting edge diagnostic & therapeutic technologies for prolonging life

Population ages Compromised defenses

high prevalence of pathogens

high prevalence of immuocompromised hosts

efficient mechanisms of transmission from patient to patient.

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The famous ancient physician Charaka and surgeon Sushuruta (Ca. 400 B.C.) emphasized the need for prevention of infection in clinical practice

1800’s typhus was considered as HAI James Simpson (1830)-termed HAI Ingaz Semmelweiss (1861) emphasised importance of

hand hygiene in prevention of puerperal sepsis Lister introduced antiseptic theory Florence Nightingale “Do no harm”- Hospital hygiene.

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Alexander Fleming -Penicillin 1943- penicillin mass production 1943- Marybaber 1946- Pn resistant strains outnumbered

sensitive ones Pn resistant strains in Op patients 1960 – Methicillin Broad-spectrum antibiotics seemed to keep

check on S.aureus infections

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The Story Of Superbug

1961-MRSA Multiple drug resistant strains VRSA Superbugs today More recently the extensive use of indwelling medical devices

and the introduction of new antibiotics coupled with their indiscriminate use the gram-positive cocci have once again emerged as the predominant causes of infection

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Superbug Returns

Nonspecific

infections common among the normal population

they follow a current regional epidemiological situation

they do not need specific preventive arrangements

Specific

resulting from diagnostical or therapeutical procedures

due to lack of personal hygiene of staff,

wrong therapeutic technique

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Endogenous (50%) Exogenous (15%) Cross infection (35%)

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Patient Factors Immunocompromised Severity of illness Broken skin & mucous membrane Length of hospital stay

Iatrogenic factors Pathogens on hands of medical personal Invasive procedure Misuse of antibiotics Acquired antibiotic resistance

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Environmental Contaminated water systems

Nurse to patient ratio

Open beds close together

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There are five main modes of transmission

Contact

Vector borne

Air borne

Droplet

Common vehicle

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DROPLET TRANSMISSIONDroplet generated by sneezingCoughing or respiratory tract procedures like

Bronchoscopy or suction

VECTOR TRANSMISSIONTransmitted through insects andOther invertebrates animalssuch as mosquitoes and fleas.

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AIR BORNE TRANSMISSIONTiny droplet nuclei that remain (<5)suspended in air.

COMMON VEHICLE TRANSMISSIONTransmitted indirectly by materials contaminated with the infections.

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VIRUS

BACTERIA

FUNGI

Bacteria Commensal Bacteria

Staph.epidermidis (iv infections)

E. coli (UTI) Pathogenic Bacteria Gram-positive

Staph.aureus- In hospitals commonly 40-50% of S. aureus isolates are MRSA

Streptococci- Streptococcus beta-hemolyticus, Strept. Pyogenes

Clostridia sp

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Gram-negative Enterobacteriaceae (e.g. E. coli, Proteus, Klebsiella, Enterobacter,

Serratia marcescens)

Pseudomonas spp.

Legionella sp

VIRUS Hepatitis B,C

Respiratory Syncytial Virus

Rotavirus

Enterovirus

Varicella Zoster09-02-2017

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FUNGI

Candida albigans

Aspergillus spp.

Cryptococcus neoformans

Cryptosporidium

PARASITES

Pneumocystis carini

Toxoplasma pneumoniae

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90% due to bacteria 10% (others: virus, fungi, protozoal etc) Most common pathogens isolated from any HAI:

S. aureus (13%)

E. coli (12%)

CoNS (11%)

Enterococci (10%)

Pseudomonas (9%)

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Most common isolated pathogens also depends on site of infection

UTI (E. coli-24%)

SSI (S. aureus-20%)

BSI (CoNS-31%)

LRI (S. aureus 19%, Pseudomonas 17%)

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Urinary tract infections (34%) Surgical site infections (17%) Pneumonia (13%) Blood stream Infection (14%) Nosocomial diarrhea Fungal infections Legionellosis

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Cell wall/membrane synthesis inhibitors

Vancomycin

Cephalosporins

Carbapenems

Teicoplanin

Daptomycin

Piperacillin+tazobactum

Colistin

Protein synthesis Inhibitors

Aminoglycosides▪ Amikacin

▪ Netilmicin

▪ Tobramycin

Tigecycline

Linezolid

Quinpristin/Dalfopristin Miscellaneous

Levofloxacin

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Glycopeptide antibiotic MOA

inhibiting proper cell wall synthesis in Gm+ bacteria by preventing cross-linking

Antimicrobial spectrum MRSA & multi-resistant Staphylococcus epidermidis (MRSE) Clostridium difficile,Corynebacterium

Indications pseudomembranous colitis , MRSA infections

Adverse effects Red man syndrome Ototoxicity, Nephrotoxicity

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β-lactam antibiotic MOA: Inhibit cell wall synthesis Drugs:

Ceftazidime (3G) Cefepime (4G) Ceftaroline (5G)

AMS: Ceftazidime : Pseudomonas, Gm-ve bacilli Cefepime : Gm-ve bacilli, MRSA, Strep.pneumonia Ceftaroline : Gm+ve , MRSA, Penicillin resistant Strep.pneumonia,

Enterococcus

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Uses: Hospital acquired pneumonia

Hospital acquired bacteremia

Hospital acquired septicemia

UTIs

Febrile neutropenic pts (4G) ADR:

Hypersensitivity reactions

Superinfections

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β-lactam antibiotics Highly resistant to β-lactamases Broad spectrum antibiotic Drugs:

Imipenem

Meropenem

Ertapenem

Doripenem MOA: Inhibits cell wall synthesis Antimicrobial Spectrum:

Gm+ve, Gm-ve, Anareobes09-02-2017

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extremely potent broad spectrum antibiotic Indications:

Hospital acquired Infections- resistant to other β-lactam antibiotics

Inactivated by renal dehydropeptidase -> given in combination with cilastatin(inhibits the human enzyme dehydropeptidase)

ADR:

Decreases seizure threshold

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MEROPENEM Newer carbapenem not deactivated by dehydropeptidase Indications: -Reserve drug for serious HAI ADR: Similar to Imipenem but less potential to induce seizures

DORIPENAM ultra-broad spectrum Indications

complex abdominal infections Nosocomial pneumonia complicated UTI including kidney infections with septicemia

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Glycopeptide antibiotic MOA : inhibits cell-wall synthesis AMS :

MRSA Listeria monocytogenes,Corynebacterium spp,Clostridium spp Nonviridans and viridans streptococci, enterococci

Uses: MRSA and penicillin resistant Strep.infections Osteomyelitis, Enterococcal endocarditis

ADR : Hypersensitivity, Skin rashes, Neutropenia

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lipopeptide antibiotic MOA

inserted into cell membrane – creates hole – leakage of ions – depolarisation- cell death AMS: Gram-positive bacteria

glycopeptide-resistant Enterococci (GRE) MRSA, streptococci , corynebacteria.

Indications skin and skin structure infections caused by Gram-positive infections Staphylococcus aureus bacteraemia

Adverse effects Hypotension, Hypokalaemia, Hyperglycaemia Thrombocytopenia, Elevated creatine kinase

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Group: polypeptide antibiotic MOA : Binds to LPSs -> Disruption of cell membrane ->leakage of

intracellular contents -> bacterial death Antimicrobial Spectrum : Gm –ve bacteria

P. aeruginosa Acinetobacter species Enterobacteriaceae

Indications: VAP, Nosocomial bacteremia

ADR: Nephrotoxicity- Lesser toxic than aminoglycosides Neurotoxicity Bronchospasm (Inhalation)- treated with salbutamol

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Group : Aminoglycoside MOA: Bids to 50 S ribosome – inhibits protein synthesis Antimicrobial spectrum:

Pseudomonas aeroginosa

Proteus, Serratia, Klebsiella, Enterobacter, E.coli Indications

Serious Gm-ve HAI

M.tuberculosis ADR:

Ototoxicity, Nephrotoxicity

Neuromuscular blockade09-02-2017

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AMS: Aerobic Gm-ve bacilli Uses: Susceptible Enterobactericea, aerobic Gm-ve bacilli ADR: Similar to Amikacin but less toxic

Uses: Ps.aeuroginosa in combination with β-lactam antibiotics

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Tobramycin

Group: glycylcycline antibiotic MOA : bacteriostatic, broad spectrum antibiotic

Binds to 30S ribosome -> inhibits bacterial protein synthesis Antimicrobial Spectrum :

methicillin-resistant Staphylococcus aureus (MRSA)

Stenotrophomonas maltophilia

Haemophilus influenza

Neisseria gonorrhea

multi-drug resistant strains of Acinetobacter baumannii

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Indications: complicated intra-abdominal and skin and soft tissue

infections Adverse Effects : diarrhoea nausea and vomiting. pain at the injection site swelling and irritation; increased or

decreased heart rate and infections. Also avoid use in children and pregnancy, due to its effects on teeth and bone.

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Group : Oxazolidinone MOA : Binds to 50S ribosome -> inhibits bacterial protein synthesis Antimicrobial spectrum:

MRSA, VRSA, VRE

Strep.vidans, pneumonia

Corynebacterium, Clostridia Indications:

Nosocomial pneumonia

SSI ADR: Neutropenia

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Group: Streptogramins MOA: Binds to 50S ribosome -> inhibits bacterial protein synthesis AMA:

Gm +ve bacteria

M. pneumoniae, Legionella spp., and Chlamydia pneumoniae Indication :reserved for treatment of serious infections caused by

multiple-drug-resistant gram-positive organisms such as vancomycin-resistant E. faecium.

ADR : Arthralgia, myalgia, Phlebitis

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2G Fluoroquinolones MOA: Inhibition of bacterial enzyme – DNA gyrase, topoisomerase IV AMS:

Gm+ve esp. Strep.pneumonia Gm-ve bacilli Atypical pathogens- Chlamydia, Mycoplasma Anaerobes

Uses : C/c bronchitis Pneumonia (CA & HA) UTI A/c sinusitis

ADR: Tendonitis, Teratogenic

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Caspofungin Echinocandin

MOA: fungal cell wall lysis

Use : Aspergillus inf, Candidiasis

ADR: Abnormal liver fn Amphotericin B

Polyene- binds to ergosterol in cell wall-> increase permeability

Uses: invasive aspergillosis, histoplasmosis, Cocoidomycosis

ADR : Nephrotoxic

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Fluconazole

Azole- inhibits ergosterol synthesis

Uses: Candidiasis, Coiccoidomycosis

Adr: GI upset

Flucytosine

Inhibits fungal DNA syn

Use; in combi for candidiasis, Crytococcosis

ADR: Bone marrow deppresion

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It is the most common cause of nosocomial infections

80% of the infections are associated with indwelling catheters.

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Mild-Moderate Ciprofloxacin 500mg po / 400mg iv Q12H

Levofloxacin 500-750mg iv/po q24h

Ceftriaxone 1g iv

Severe Cefepime 2g iv q12h

Ceftazidime 2g iv q8h

Piperacillin+tazobactum 3.375-4.5giv q6h

Carbapenems

vancomycin

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Hooton TM. Nosocomial urinary tract infections. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. New York, NY: Churchill Livingstone; 2010:3725-3737

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Fluconazole 200-400mg/day x 14dif resistant

Oral flucytosine &/or Parenteral Amphotericin B Bladder irrigation with Amphotericin B is NOT recommended Fluconazole iv 200mg/day

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The incidence is increasing particularly for certain organisms such as multi resistance coagulase negative staphylococcus and candida.

Infections may occurs at the skin entry site of the IV device or in the sub cutaneous path of catheter.

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A thin coating containing biologically active agents, which coats the surface of structures such as teeth or the inner surfaces of catheter, tube, or other implanted or indwelling device. It contains viable and nonviable microorganisms that adhere to the surface and are trapped within a matrix of organic matter (for example, proteins, glycoproteins, and carbohydrates).

09-02-2017 Farlex Partner Medical Dictionary

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Simple Multi drug resistant

Coagulase –ve Staph. Semisynthetic Penicillins Vancomycin

Staph.aureus Penicillin, Cefazolin Vancomycin

Gm-ve FQ FQ+rifampin

Pseudomonas

Candidia Fluconazole Amphotericin_B

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They are also frequent

The definition is mainly clinical(purulent discharge around wounds

or the insertion site of drain, orspreading cellulites from wounds)

The infections can be exogenously or endogenously

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+ Vancomycin 1g iv Q12H

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Wound infection without sepsis ( not GIT, FGT) Mild-Moderate

Cephalexin 500mg po QID

Augmentin 875/125mg po BD

Doxycyline 100mg po BD Complicated

Ticarcillin + Clav 3.1g iv Q6H

Piptaz 3.375g iv Q6H

Ertapenem 1g Q24H

Wound infection with sepsis ( not GIT, FGT) Ampicillin + sulbactum 1.5-3g iv Q6H Ticarcillin + Clav 3.1g iv Q6H Piptaz 3.375g iv Q6H Cephazolin 1g iv Q8H

Wound Infection (GIT , FGT) Ampicillin + sulbactum 1.5-3g iv Q6H Ticarcillin + Clav 3.1g iv Q6H Piptaz 3.375g iv Q6H Ceftriaxone+metronidazole Imipenem 500mg iv Q6H

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Recommendations

Administer within 1 hour of incision to maximize tissue concentration

▪ Once the incision is made, delivery to the wound is impaired

Duration of prophylaxis

Stop prophylaxis

▪ within 24 hours after the procedure

▪ within 48 hours after cardiac surgery

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Bratzler et al Arch Surg 2005, 140:174-82

Harbarth S et al. Circulation 2000;101:2916–2921

Primary Alternate

Cardiac Cefazolin +/- Gentamicin Vancomycin +/- Gentamicin

GIT Cefazolin(or) Cefoxitin +/-Metronidazole

Clindamycin + Gentamicin

GUT Ampicillin +/- Gentamicin +/-Cefazolin

Clindamycin + Gentamicin

OBG Cefazolin Clindamycin + Gentamicin

Head & Neck Cefazolin Clindamycin + Gentamicin

Neurosurgery Cefazolin Vancomycin

Ophthal Gentamicin, tobramycin,Moxifloxacin, gatifloxacin

Ortho Cephazolin Clindamycin/ Vancomycin

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The most important are patients on ventilators in ICU.

Recent and progressiveradiological opacities of thepulmonary parenchyma, purulent sputum and recent onsite fever.

Most commonly caused by acinetobacter.

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Hospital-acquired pneumonia (HAP) Occurs 48 hours or more after admission, which was not incubating at the time of admission

Healthcare-associated pneumonia (HCAP) is defined as pneumonia that occurs in a non-hospitalized patient with extensive healthcare contact, as defined by one or more of the following: Intravenous therapy, wound care, or intravenous chemotherapy within the prior 30 days. Residence in a nursing home or other long-term care facility Hospitalization in an acute care hospital for two or more days within the prior 90 days Attendance at a hemodialysis clinic within the prior 30 days

Ventilator-associated pneumonia (VAP) Arises more than 48-72 hours after endotracheal intubation

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Non-MDR Pathogens MDR Pathogens

Streptococcus pneumoniae Pseudomonas aeruginosa

Other Streptococcus spp. MRSA

Haemophilus influenzae Acinetobacter spp.

MSSA Antibiotic-resistant Enterobacteriaceae

Antibiotic-sensitive Enterobacteriaceae Enterobacter spp.

Escherichia coli ESBL-positive strains

Klebsiella pneumoniae Klebsiella spp.

Proteus spp. Legionella pneumophila

Enterobacter spp. Burkholderia cepacia

Serratia marcescens Aspergillus spp.

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Patients without Risk Factors for MDR Pathogens

Ceftriaxone (2 g IV q24h) or

Moxifloxacin (400 mg IV q24h), ciprofloxacin (400 mg IV q8h), or levofloxacin (750 mg IV q24h) or

Ampicillin/sulbactam (3 g IV q6h) or

Ertapenem (1 g IV q24h)

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Patients with Risk Factors for MDR Pathogens

1. A β-lactam:Ceftazidime (2 g IV q8h) or cefepime (2 g IV q8–12h) orPiperacillin/tazobactam (4.5 g IV q6h), Imipenem (500 mg IV q6h or 1 g IV q8h), or

meropenem (1 g IV q8h) plus

2. A second agent active against gram-negative bacterial pathogens:Gentamicin or tobramycin (7 mg/kg IV q24h) or amikacin (20 mg/kg IV q24h) orCiprofloxacin (400 mg IV q8h) or levofloxacin (750 mg IV q24h) plus

3. An agent active against gram-positive bacterial pathogens:Linezolid (600 mg IV q12h) orVancomycin (15 mg/kg, up to 1 g IV, q12h)

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Etiology : Cl. Difficle

Antibiotics associated : Clindamycin

Ampicillin

Cephalosporins

Fluoroquinolones Transmission

Acquired exogenously in hospitals

Transmitted through infected stools of patients or carriers

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Initial episode Mild to mod

Tab. Metronidazole 500mgTID X 10-14d Severe

Tab. Vancomycin 125mg QID X 10-14d Fulminant

Tab. Vancomycin 500mg + Inj. Metronidazole 500mgiv Q8H

+rectal instillation of Vancomycin (500mg in 100ml NS) as retention enema Q6-8H

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First : Similar to initial episode Second : Vancomycin tapering regime

125mg QID x 10-14d; BID x 7d ; OD x 7d ; Q2-3d x 2-8 weeks

Multiple :

Vancomycin tapering regime

Vancomycin 500mg QID x 10d + Saccharomyces boularetii 500mg BID x 28d

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Etiology:

Candida

Aspergillosis

Candida

Echinocandin : Caspofungin

Fluconazole

Amphotericin B

Fluconazole+Amphotercin B

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Aspergillosis

Voriconazole

Liposomal AMB

Caspofungin/Micafungin

Posiconazole

Itraconazole

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Hand washing Isolation Sterilization Gloves and aprons

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Prevention of Central Venous Catheter Infections Educate personnel about catheter insertion and care.

Use chlorhexidine to prepare the insertion site.

Use maximal barrier precautions during catheter insertion.

Consolidate insertion supplies (e.g., in an insertion kit or cart).

Use a checklist to enhance adherence to the bundle.

Cleanse patients daily with chlorhexidine.

Ask daily: Is the catheter needed? Remove catheter if not needed or used.

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Prevention of Ventilator-Associated Pneumonia and Complications Elevate head of bed to 30–45 degrees. Decontaminate oropharynx regularly with chlorhexidine. Give "sedation vacation" and assess readiness to extubate daily. Use peptic ulcer disease prophylaxis.

Prevention of Surgical-Site Infections Administer prophylactic antibiotics within 1 h before surgery; discontinue within

24 h. Limit any hair removal to the time of surgery; use clippers Prepare surgical site with chlorhexidine-alcohol. Maintain normal perioperative glucose levels (cardiac surgery patients)

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Prevention of Urinary Tract Infections Place bladder catheters only when absolutely needed (e.g., to relieve

obstruction), not solely for the provider's convenience.

Use aseptic technique for catheter insertion and urinary tract instrumentation.

Minimize manipulation or opening of drainage systems.

Ask daily: Is the bladder catheter needed? Remove catheter if not needed.

Prevention of Pathogen Cross-Transmission

Cleanse hands with alcohol hand rub before and after all contacts with patients or their environments.

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Razupenem 2G glycopeptides

Telavancin- sup. To Vancomycin in Rx MRSA Dalbavancin - sup. To Vancomycin in Rx catheter BSI Oritavancin – VRSA , VRE

Ramoplanin Cl.difficle, VRE

Torezolid Staph., Enterococci, More potent than Linezolid Phase III trial

Cephalosporins 5G Ceftobiprole

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The progressive emergence of gram-positive organisms as dominant isolates in nosocomial infections has become a primary health care concern

Antibiotic therapy regimens should balance the care of individual patients and the general patient population welfare.

Antibiotic treatment should start as soon as possible after infection is diagnosed and its duration should be minimized

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Monotherapy Conventional Combination Alternatives

E.coli Ceftazidime,CefepimeAmox-clav,FQ

Cefotaxime+ AmikacinPiperacillin+ Tazobactum

ImipenemImipenem+ AG/FQ

Klebsiella spSBL -

CeftazidimeCefipimeAmox-clav

Cefotaxime+ AmikacinPiperacillin+ Tazobactum

ImipenemImipenem+ AG/FQ

ESBL+ Imipenem,CefapimeFQ

Imipenem+AGPiperacillin+Tazobactum + Amikacin

Imipenem+FQ

Enterobacter

ImipenemCefapime,Piptaz

3G Cephalosporin+AG Imipenem+FQAG+FQ

Pseudomonas

Piperacillin3G,4G CephalosporinCarbapenem

Ticarcillin/ceftazidime+Sulbactum+AGCefftazidime+FQ

Piperacillin+FQAG+FQ

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Monotherapy Conventionall combinations

Alternatives

MRSA VancomycinImipenem+cilastinMeropenem

Vancomycin+FQRifampicin+Vancomycin

Imipenem+Vancomycin

Staphylococci(Coaagulase-ve)

VancomycinImipenem+cilastinMeropenem

Vancomycin+FQRifampicin+Vancomycin

Imipenem+FosfomycinAG

Entercoccus AmpicillinImipenemPiperacillinVancomycin

Ampicillin+GentamicinVancomycin+AG

Teicoplanin+ piperacillinImipenem +vancomycin

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Harrison’s principles of internal medicine , 18th edition Goodman and Gilman's the pharmacological basis of therapeutics 12th edition Atul Jain, Kanwardeep Singh, Vol. 9 No. 1, January-March 2007, Recent Advances in

the Management of Nosocomial Infections Basic & Clinical pharmacology , 12th Ed., Betram g. Katzung Leu HS, Huang CT. Clearance of funguria with short-course antifungal regimens: a

prospective, randomized, controlled study. Clin Infect Dis 1995;20:1152-7 Oxford textbook of medicine 4th edition Principles of Pharmacology 2nd edition, HL Sharma KK Sharma WHO Prevention of hospital-acquired infections 2nd Edition Prevention & Management of Catheter Associated UTI-Diane K. Newman http://www.optimusise.com/history-hospital-infection http://www.ncbi.nlm.nih.gov/pubmed/

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