Pathogen, Resistance, and Antimicrobial Stewardship

Antimicrobial Stewardship

Coordinated interventions designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug regimen, dose duration of therapy, and route of administration

Hygiene Hypothesis

Lack of early childhood exposure to infectious agents, symbiotic microorganisms, and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system

Main goal for antimicrobial stewardship

Define and implement antimicrobial stewardship activities in all settings like office-based practices, outpatient, ED, nursing home, pharmacies, and correctional facilities.

Antimicrobial stewardship strategies

Prospective audit and feedback, formulary restriction, guidelines and clinical pathways, antimicrobial order forms, IV to PO conversion, de-escalation of therapy, dose optimization, education

Where does most antimicrobial misuse occur

Long term care

Goals of antimicrobial stewardship

Optimize clinical outcomes, minimize unintended consequences (AEs/resistance), improve cost-effectiveness

Prospective Audit and Feedback

Antimicrobial use reviewed and recommendations made to optimize use. Evaluate antimicrobial use after it has been initiated. Recommendations are voluntary

Formulary restriction and preauthorization

Antimicrobials are made accessible only through an approval process. Use is restricted before therapy is initiated. Team member receives requests for restricted antimicrobials. Approves or recommends alternative drug.

Parenteral (IV) to Oral (PO) conversion

Patients with infections serious enough to require hospitalization usually initially require parenteral therapy but once the patient improves and meets clinical criteria they can convert to PO therapy.

Antibiotics with adequate oral bioavailability

Azithromycin, Clindamycin, fluoroquinolones, fluconazole, linezolid, metronidazole

Candidates for IV to PO step down

Infection is treatable with PO antibiotics. GI tract is functioning. No evidence of malabsorption, dysphagia, or GI bleed. Patient is hemodynamically stable, patient is improving clinically

Contraindications for IV to PO step down

The patient has a severe infection. Oral antimicrobial may not achieve adequate concentration at the site of infection. Infection is caused by resistant organism. The oral route is unreliable or unavailable

What is a virus

Simple organisms that take over host cells. On their own viruses can not grow, reproduce, or metabolize. Composed of DNA or RNA.

What is a bacteria

Microscopic organism that have a rigid outer cell wall.

What is a fungus

Larger plant like organisms that can be absorb from food.

Normal flora

Non disease causing, found in healthy individuals. Usually extremely abundant in terms of numbers. Found mostly on the skin, eyes, nose, mouth, upper throat, lower urethra, and the large intestine

Purpose of normal flora

Helps stimulate the synthesis of normal antibodies, prevent attachment and penetration of pathogenic microorganisms, digestion, produce vitamins, stimulation cell maturation, aid in intestinal transit and colonization resistance

Common gram positive bacteria found on individuals

Staphylococcus epidermidis, streptococcus, enterococcus.

Common gram negative bacteria found on individuals

E. coli, klebsiella, Neisseria, Hemophilus, prevotella

Common anaerobes found in individuals

Corynebacterium, Propionibacterium, lactobacillus, clostridium

Bacterial Cell Wall Anatomy

Gram negative have an outer lipopolysaccharide outer membrane, peptidoglycan layer, and a phospholipid layer.

Gram positive only have peptidoglycan layer and phospholipid layer

Purpose of biofilms

Allows bacteria to stick together a form a layer of protection against antibiotics. Staph aureus produces biofilms.

Staphylococcus Characteristics

Gram positive cocci clusters, some with capsules

Staphylococcus transmission

Skin to skin contact

Diseases caused by staphylococcus aureus

Boils, skin sepsis, wound infections, scalded skin syndrome, catheter associated disease, foodborne infection, endocarditis, osteomyelitis, TSS, pneumonia

Complication of Staph aureus

MRSA. Resistant to beta lactams.

Anti-MRSA antibiotics

Empiric, active against almost all MRSA. Vanco, telavancin, oritavancin, dalbavancin, linezolid, tedizolid, daptomycin, tigecycline, ceftaroline, delafloxacin

Less effective anti-MRSA antibiotics

TMP/SMX, doxycycline, clindamycin

Staphylococcus Epidermis

Gram positive clusters

Skin to skin transmission

multi-drug resistant

Disease caused by staphylococcus epidermidis

Device related sepsis, UTI, sternal wound osteomyelitis, prosthetic valve endocarditis, artificial joint infections

Staphylococcus Saprophyticus

Gram positive cocci clusters

Skin and GU mucosa colonizers

Can spread to urinary tract and cause UTIs in women

Streptococcus Pneumoniae

Gram positive diplococci

Colonizes in URT through droplet spread

Can be prevented through vaccination/handwashing

Diseases caused by streptococcus pneumoniae

Pneumonia, septicemia, meningitis, otitis media, sinusitis

Common bacterial pathogens that cause upper respiratory tract infections

Streptococcus pneumoniae, haemophilus influenzae, moraxella catarrhalis

Streptoccus pyogenes

Gram positive cocci chains

Colonizes URT and skin spread by droplets and contact

Can cause URI, SSTI, Scarlet fever, necrotizing fasciitis, rheumatic fever, glomerulonephritis

Enterococcus spp.

Gram positive cocci in pair and chains

Colonizes gut of humans and animals

Can cause UTI, endocarditis, bacteremia, wound infections

Prevention via proper sanitation

Enterobacterales

Enteric gram-negative bacteria that often colonize the genitourinary tract. Resistant gram-negative bacteria are recognized as a serious threat to public health.

Escherichia Coli

Gram negative rod

Transmission by contact or ingestion

Can cause URI, diarrhea, neonatal meningitis, sepsis, wound infections

Complications: increasing resistance

Prevention through proper food preparation and sanitation

Klebsiella, Serratia, Enterobacter spp.

Gram negative rods, kleb is a capsule

Spread by contact

Can cause UTI, pneumonia, bacteremia

Prevention via handwashing and isolation

Classes of Beta-Lactams

Semi-synthetic penicillin’s

Generation Cephalosporins (1-4)

Monobactams (aztreonam)

Carbapenems (meropenem, imipenem, doripenem)

Beta lactamases

Are enzymes that open the beta-lactam ring inactivating the antibiotic

Extended Spectrum Beta Lactamases (ESBLS)

Enzymes that break down many common beta lactam antibiotics making the antibiotics ineffective. Infections with ESBL producing organisms have been associated with poor outcomes. Carbapenems constitute the best treatment option for infections caused by ESBL’s.

Examples of ESBLS

E. Coli and K. pneumonia

CRE

Carbapenem resistant enterobacterial are in gram - bacteria. No beta lactam drugs will work against these organisms.

Salmonella spp.

Gram negative motile, non-sporing rods

Not colonized in gut. Acquired through ingestion

Causes severe diarrheal illness and sometimes bacteremia

May lead to carrier status

Prevention is through proper food preparation and sanitation

Pseudomonas Aeruginosa

Gram negative rod, motile, grows in many conditions

Colonizes in gut spread by contact in environment

Can infect any tissue and cause osteomyelitis, endocarditis, UTI

Very resistant

Prevention includes isolation, hand washing, and avoiding broad spectrum agents

Haemophilus Influenzae

Gram negative cocco-bacillus, non-motile

Colonizes URT, airborne transmission

Can cause meningitis, pneumonia, osteomyelitis, otitis media, sinusitis

Prevented through vaccination

Pasteurella Multocida

Small gram negative cocco-bacilli

Found in the mouths of animals

Can infect bites

Prevention is animal and human dental care

Vibrio Spp

Curved gram-negative rods, highly motile

Transmitted through contaminated water or food

Causes cholera, watery diarrhea, wound infections, and bacteremia

Can also lead to death and necrotizing fasciitis

Prevention: avoid contaminated water

Legionella Pneumophila

In tissue gram negative coccobacilli

Transmitted via environmental contamination or inhalation of contaminated water from showers

Causes pneumonia

Prevention through water systems

Moraxella Catarrhalis

Gram negative cocci

Pathogen of the RT

Can cause bronchitis, pneumonia, otitis media, sinusitis

Most strains produce beta lactamases

Bordetella Pertussis

Small gram negative cocco-bacillus

Airborne transmission

Can cause whooping cough

Prevented through vaccination

Bacteroides Fragilis

Small gram negative rods, anaerobic, non-motile

Transmitted through endogenous gut/fecal contamination of wounds

Can cause intra-abdominal abscess, sepsis, aspiration pneumonia, brain abscesses

Prevention good antimicrobial prophylaxis

Clostridioides Difficile

Slender gram-positive anaerobic rod, motile, spore forming

Spread by contact, grows when normal gut flora is diminished

Causes pseudomembranous colitis

Prevention includes handwashing, isolation, and avoiding antibiotics `

How does C.Diff infect someone

Both spores and vegetative cells are ingested. The vegetative cells are killed by stomach acid while the spores germinate in the small bowel. The bacteria multiply in the colon and produces toxins A and B. The toxins lead to increased permeability of the intestine and epithelial cell apoptosis. This results in colitis and watery diarrhea

Gardnerella Vaginalis

Gram variable anaerobic bacilli

Transmitted through sexual contact

Causes BV

practice safe sex

Treponema Pallidum

Coiled spirochetes

transmitted through very close contact

causes syphilis and can lead to cardiac and CNS complication

Practice safe sex

Mycoplasma Spp.

Lacks cell wall

Airborne transmission

Causes pneumonia and sometimes genital infections

Difficult to prevent spread

Chlamydia Spp.

Obligate intracellular parasite

Transmitted through inhalation and sexual contact

Causes chlamydia, eye infections, pneumonia

Eventually can lead to PID and infertility

Practice safe sex

Candida Albicans

Opportunistic pathogenic yeast

Detected in the mouth and GI tract

Can become pathogenic in immunocompromised individuals

Coronavirus

Single stranded RNA virus. Has the longest genome of any RNA virus. Primarily infects the URT. Transmission through respiratory droplets. A lot of variation that increases efficient transmission and reduces antibody binding.