Antibiotics JOHN D. MORRIS, MD

HOSPITALIST

http://www.cdc.gov/getsmart/community/for-hcp/outpatient-hcp/adult-treatment-rec.pdf

Adult Treatment Recommendations Antibiotic prescribing guidelines establish standards of care and focus quality improvement efforts. The table below summarizes the most recent recommendations for appropriate antibiotic prescribing for adults seeking care in an outpatient setting.

The Chain of Infection Understanding Medical Surgical Nursing, 4th Ed. Williams+ Hopper

Causative agent --- Reservoir---Mode of transmission--- Portal of entry--- Susceptible host --- Portal of exit

Causative agent

u  Bacteria

u  Virus

u  Fungus

u  Protozoa

u  Helminth

u  Prion

u  A. Normal flora- the microbiome

u  B. Pathogens- the bad guys

Mode of transmission

u  Direct contact- touch, bite, kiss, sex, droplets

u  Indirect contact- “vehicle contact”

u  Airborne- Fountain, fan, other air sources

u  Fomites- clothes, etc.

Prevention

u  Hand hygiene

u  Aseptic technique

u  PPE (personal protective equipment)- gloves, asks, goggles, gowns, shoe covers, etc.

Indirect contact (clean the vehicles!)

u  Prevention

u  Hand hygiene

u  Excellent cleaning

u  Stethoscopes

u  Clean water, food

u  Phones, tablets, keyboards

Portal of entry

u  ENTRY into Susceptible Host

u  Respiratory Tract

u  Skin

u  Mucous Membranes

u  Gastrointestinal Tract

u  Genitourinary Tract

u  Placenta

Susceptible Host Some breakdown of defense (usually)

u  Very young or very old

u  Malnourished

u  Immunocompromised

u  Chronic disease

u  Stress

u  Catheters (PICC, Foley, NG)

u  Invasive procedures

u  Antibiotics

u  Steroids

Exit portal

u  Route Infectious agent uses to leave host who has become reservoir

Reservoir

u  Environmental home for infectious agent

u  Animate: People, Insects, Animals, Plants

u  Inanimate: Water, Soil, Medical devices

Sir Alexander Fleming

u  British Microbiologist

u  Discovered Penicillin

u  Won Nobel Prize in medicine in 1945

Excerpt from Nobel Lecture 1945

“It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing occasionally happened in the body…and by exposing his microbes to non-lethal quantities of the drug make them resistant.”

Sir Alexander Fleming

Sobering thought

u  US FDA approval of new antibacterials is down 56% from 1983-2002

and its much less since then…

u  Infectious disease are still the most common cause of death

u  ?Post-antibiotic era?- yes, we are pretty close

u  Therefore, we must manage carefully and responsibly what we have.

Maybe yours?

MIC Minimum inhibitory concentration

u  Amount of antibiotic required to stop growth of the bacteria

u  Usual reported number

u  Used to identify sensitivity.

u  A concentration, varies depending on different “compartments” in the body

u  Examples: Sinus fluid, alveolar fluid (lung), bone, skin/soft tissue, blood, intestinal lumen

MBC Minimum Bacteriacidal Concentration

u  Minimum amount of an antibiotic required to KILL the bug

u  Almost always different than the MIC

u  “Static drugs”- MIC low, MBC very different- stop bugs from growing, rely on body’s defences to kill them

u  “’Cidal drugs”- MIC low, MBC close to same- required when the immune system can’t get to the bug

Disc diffusion

Time dependent killing

u  Antibiotic only effective while the concentration where the bug is located is above the MIC

u  Certain very important antibiotics work this way.

u  Beta lactams (cephalosporins, penicillins, carbapenems)

u  Vancomycin

Every time the antibiotic gets below the MIC, the germs can grow back and usually, the partially resistant ones grow back!!

Dose dependent killing

u  Long “post-antibiotic dose effect”- the peak level in the environment of the bacteria is most important part of getting these antibiotics to work.

u  Some very important antibiotics work this way

u  Quinolones (Cipro, Avelox, Levaquin)

u  Aminoglycosides (Tobramycin, Gentamycin, Amikacin)

Antibiotics Beta-lactams

Beta lactam antibiotics

u  Penicillin

u  Derivatives- Ampicillin, amoxicillin, cloxacillin, dicloxacillin, nafcillin, ticarcillin, piperacillin, oxacillin, carbenacillin, etc

u  Carbapenems- imipenem (primaxin), ertapenem (invanz), doripenem (doribax), meropenem (merrem)

u  Cephalosporins- cephalexin (Keflex), cefazolin (ancef), cefuroxime (zinacef), ceftriaxone (rocephin), cefotaxime (claforan) Cefepime (Maxepime), Cefotetan (cefotan)

u  Ceftaroline (Teflaro

u  Aztreonam- (azactam)

Penicillins

u  Most bactericidal antibiotics available

u  Cleared by the kidney mostly, some by the liver.

u  Allergy- rash

u  Allergy- mononucleosis and ampicillin

u  Allergy- anaphylaxis- swelling, BP drops, unstable, patient can die

Treatment for anaphylaxis- epinephrine

Have to monitor Kidney function- if renal function changes, excretion changes, and levels can change causing side effects.

Cephalosporins

u  Very broad spectrum. Well tolerated.

u  5% cross reactivity with PCN anaphylaxis.

u  Can cause seizures and weird behavior if levels get too high.

u  Have to dose based on kidney function.

Ceftaroline- Teflaro

u  Only B-lactam to kill MRSA

u  Hasn’t been out long enough to have the studies to back it up (yet?)

u  Can cause anemia like the other B-lactams

Carbapenems

u  Very broad spectrum

u  Kill resistant Gram negative organisms, enterococcus, anaerobes.

u  All can cause CNS side effects- Seizures

u  30% cross reactivity with PCN anaphylaxis!!!

u  30% cross reactivity with PCN anaphylaxis!!!

u  Cause seizures if not dosed appropriately for renal function.

Aztreonam (Azactam)

u  NO cross reactivity with other B- lactam anaphylaxis

u  Only gets Gram negatives, NO OTHERS

u  Side effects few and mild for most part

Vancomycin

u  Very broad spectrum against resistant Gram positive organisms

u  MRSA, Enterococcus, Pneumococcus, Staph epidermidis

u  MIC vs MBC

u  Fast infusion- “Red man” syndrome- NOT an ALLERGY!

u  Ototoxic, nephrotoxic

u  Doesn’t penetrate lungs or bone well.

u  Cleared by the kidney, have to monitor renal function

u  ZERO oral absorption, only used orally for C. diff

Daptomycin (Cubicin)

u  Works differently from all the other antibiotics

u  Attatches to phosphatidylglycerol in bacterial cell wall, pokes through the membrane, and aggregates making pores that allow the electric charge across the membrane to discharge. It almost literally “shorts out” the bacteria. Most rapidly cidal antibiotic.

u  DOES NOT penetrate into lung fluid, can’t use for most pneumonia.

Linezolid (Zyvox)

u  Works well for MRSA, also VRE.

u  Main problem is drug interactions

u  SSRI- Celexa, Prozac, Zoloft, Luvox, Paxil

u  Tramadol, Trazodone, Demerol, Effexor, Cymbalta

u  Smoked sausages, red wine

u  Serotonin syndrome- altered mentation, agitation, fever, blood pressure fluctuation.

Metronidazole (Flagyl)

u  Works by inhibiting DNA of microbial cells, only anaerobes, trichomonas and amebae

u  Cleared by kidney

u  Multiple side effects, nausea, confusion (especially elderly), headache, dizziness, metallic taste. Hard on veins

Aminoglycosides Gentamycin, Tobramycin, Amikacin

u  IV only

u  Most common use long term is with another antibiotic for endocarditis

u  Renal excretion- have to monitor renal function AND levels!

u  Very prone to toxicity

u  Nephrotoxic, ototoxic most concerning.

u  Dose-dependent killing, time dependent toxicity.

u  Dose once daily for inpatients, but for synergism, dose 2-3 times/day

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Handwashing or foam?

u  SOAP and WATER after ANY exposure to someone with C. diff. Even just stepping in the room and touching the door knob!

u  SOAP and WATER after any visible or palpable exposure or if unsure

u  Foam/spray only if no visible or palpable exposure.

u  Every time

u  Before you touch your phone, stethoscope, face, ANYTHING

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Sir Alexander Fleming New York Times June 26, 1945

u  “The microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred our…. In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin- resistant organism. I hope this evil can be averted.”

When Antibiotics?

u  Acute Rhinosinusitis (cold)

u  Acute Uncomplicated Bronchitis (chest cold)

u  URI (cold)

u  Pharyngitis (sore throat)

u  Acute uncomplicated cystitis (bladder infection)

Acute Rhinosinusitis 1 in 8 adults got a diagnosis of rhinosinusitis in last 12 months 98% are viral, antibiotics not guaranteed to help even if bacterial.

May be bacterial if

Severe, >3-4 days with fever>102.0 F, purulent discharge and facial pain

Persistent >10 days without improvement

Worsening in 3-4 days

Sinus X-rays not needed, can’t differentiate viral from bacterial.

Acute Uncomplicated Bronchitis “Chest Cold”

u  Cough is most common symptom adults visit their doctor for every year. Bronchitis most common diagnosis. Almost ALL viral.

u  Evaluation rules out pneumonia.

u  Colored sputum does NOT mean bacterial infection

u  For most cases- don’t need CXR

Common Cold Non-specific URI

u  3rd most frequent diagnosis for primary care office visits.

u  All viral

u  Over 200 viruses cause common cold

u  Symptoms- Fever, cough, rhinorrhea, nasal congestion, postnasal drip, sore throat, headache, myalgias.

u  No benefit from antibiotics in uncomplicated presentation.

Pharyngitis “Sore throat, ‘Strep’ throat”

u  Streptococcal or Gonococcal etiologies only indication for antibiotics.

u  5-10% of adult sore throat is bacterial.

u  Centor Criteria

u  Exudate or swelling of tonsils

u  Tender anterior cervical lymph nodes

u  Fever >100.4

u  ABSENT cough

IDSA guidelines recommend NO antibiotics until culture positive or rapid strep antigen test is POSITIVE

Acute Uncomplicated Cystitis “Bladder infection” u  One of most common infections, usually caused by E. coli

u  Antibiotics indicated to cover this organism WHILE WAITING ON CULTURES

Just a last thought about microbiome…