Week 8: Bacterial Infections & Beta-Lactam Antibacterials PDF

**Week 8: Bacterial Infections & Beta-Lactam Antibacterials** 5 cardinal Signs of inflammation -- pain (algesia), heat (warmth), redness (erythema), swelling (edema), loss of function + swollen lymph node / purulence Systemic Manifestations: - Pyrexia - Malaise - Fati...

**Week 8: Bacterial Infections & Beta-Lactam Antibacterials** 5 cardinal Signs of inflammation -- pain (algesia), heat (warmth), redness (erythema), swelling (edema), loss of function + swollen lymph node / purulence Systemic Manifestations: - Pyrexia - Malaise - Fatigue, weakness - Anorexia - Elevated or Decreased WBCs (elevated: bacteria, decreased: viruses) Bacterial Characteristics - Peptidoglycan cell wall - Thick = **[Gram +]** bacteria (Ex: *Staphylococcus aureus, Streptococcus pneumoniae, Clostridium difficile)* - Thin = **[Gram -]** bacteria (Ex: *Neisseria gonorrhoeae, H. pylori, E.coli)* - Aerobic vs. Anaerobic - Require oxygen for growth (skin infection) vs Survival with limited oxygen supply (deeper tissue). Pathogens can be *both*! - Capsules - Some may be encapsulated, which make them resistant to **[phagocytosis]** Bacterial Pathogenicity -- how bacteria can exert 1\. Survival - Burden of their presence, transport to a new host 2\. Inflammation - Stimulating the inflammatory response 3\. If encapsulated: Resistance to immune defense 4\. Endotoxins - Found in [Gram -] cell walls, causes massive inflammation; poison ( massive inflammation) 5\. Endospores - Lay dormant in extreme environments and emerge to infect later when opportune. 6\. Exotoxins - Produced to promote host cell dysfunction and destruction Clinical Manifestations of Bacterial Infections - Fever & Chills - Endotoxins released by ***[pyogenic]*** bacteria - Leukocytosis -- Elevated **[WBCs]** - Sepsis and Shock -- When left untreated - Nausea, Vomiting, Diarrhea -- To expel toxins - Organ toxicity - Via exotoxins and enzymes: hepatotoxins, neurotoxins, enterotoxins - Inflammation - Can be localized or systemic Determining Treatment - Culture -- Identify the pathogen - Sensitivity - Identify which anti-infectives will kill the pathogen - ***Always* draw [blood cultures] prior to administering antibiotics!** - **We will treat with broad-spectrum antibiotics until results!** Antibiotic Resistance - The ability of certain bacteria to survive and multiply in the presence of antibiotics - Major public health concern! - Prevention is key - No antibiotics for viruses - Take exactly as prescribed, for full course - Hand hygiene/preventing infection and spread +-----------------------------------+-----------------------------------+ | | **Beta-Lactam Antibacterials** | +===================================+===================================+ | | **Penicillins, Ampicillin** | +-----------------------------------+-----------------------------------+ | | Bind to proteins in the cell | | | wall which creates defects (punch | | | holes) in the structure, causing | | | leakage and cell death | | | **bactericidal**! | | | | | | Contain a beta-lactam ring (+ | | | beta-lactamase inhibitor -- makes | | | it more effective) | +-----------------------------------+-----------------------------------+ | Pharmacokinetics: | Widely distributed. Can | | | penetrate CSF (cerebrospinal | | | fluid) when **meninges** are | | | inflamed | | | | | | Inactivates in **acidic** | | | environments PO: need to drink | | | with a full glass of water to | | | dilute stomach acid | | | | | | Empty stomach is recommended, | | | but with food can resolve GI | | | upset (delay absorption) | +-----------------------------------+-----------------------------------+ | M/A | Inhibits bacterial cell wall | | | synthesis to cause leakage of | | | cellular contents and cell death | +-----------------------------------+-----------------------------------+ | Indication | ***[Broad-spectrum] | | | coverage*** | | | | | | - Gram + bacterial infections: | | | *Staphylococcus, | | | Streptococcus, Enterococcus* | | | | | | - Gram - bacterial infections: | | | *E.coli, Salmonella* | | | | | | - Surgical prophylaxis (within | | | 60 mins of incision -- | | | cephalosporin, penicillin) | +-----------------------------------+-----------------------------------+ | Contraindication | Hypersensitivity to *ANY* drugs | | | in penicillin class (penicillin | | | -- Cephalosporins: | | | cross-sensitivity) | | | | | | Hypersensitivity to | | | **[cephalosporins]**, | | | carbapenems [ ] | +-----------------------------------+-----------------------------------+ | Adverse effect & Nursing | Abd pain, N/V/D -- lead to | | implications | Pseudomembranous colitis (C. | | | Diff, superinfection) without | | | helpful microbial flora, gut | | | doesn\'t function as well Give on | | | empty stomach with full glass of | | | water | | | | | | Nephropathy -- Caution with | | | renal impairment & elderly | | | Monitor serum | | | **[BUN]**, | | | **[Creatinine]**, | | | K^+^ and Na^+^ | | | | | | Rash (most common) Determine if | | | simple rash or hypersensitivity | | | reaction | +-----------------------------------+-----------------------------------+ | Patient Education | Do not take if allergy to any | | | Penicillin | | | | | | Take on an empty stomach w/ | | | full glass of water | | | | | | Do not take with | | | **[acidic]** | | | beverages | | | | | | Notify provider of new rash, | | | dyspnea | | | | | | Notify provider of any watery, | | | malodorous diarrhea | | | | | | Complete the full course of | | | treatment | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | | **Cephalosporins** | +===================================+===================================+ | | **Cefazolin** | +-----------------------------------+-----------------------------------+ | | **Does not penetrate CSF well** | | | | | | Rapid onset surgical | | | prophylaxis | | | | | | No hepatic metabolism No | | | hepatotoxicity related | | | | | | Crosses into placenta and into | | | **[chest milk]** | | | Notify the provider if they do | | | chest feeding | +-----------------------------------+-----------------------------------+ | M/A | Binds to protein of bacterial | | | cell wall to inhibit cell wall | | | synthesis (but doesn\'t punch | | | holes) **bactericidal**! | +-----------------------------------+-----------------------------------+ | Indication | Surgical prophylaxis | | | | | | Gram +: Streptococcus, | | | Methicillin-susceptible | | | Staphylococcus | | | | | | Infections of respiratory, | | | urinary tracts, skin, and sepsis | | | (as indicated by C&S) | +-----------------------------------+-----------------------------------+ | Contraindication | Hypersensitivity to | | | cephalosporins | | | | | | Hypersensitivity to penicillins | | | | | | MRSA infection (not effective) | | | | | | Caution: Renal Impairment, | | | concomitant use of nephrotoxic | | | drugs **(aminoglycosides, | | | vancomycin, furosemide)** | +-----------------------------------+-----------------------------------+ | Adverse effect | N/V/D | | | | | | Hypersensitivity | | | | | | Superinfections | +-----------------------------------+-----------------------------------+ | Nursing implications | IV, only with **[Normal | | | Saline]** (LR has | | | calcium bind with drug and | | | precipitate goes into | | | bloodstream) | | | | | | Give w/ food or | | | **[milk]** to | | | minimize GI upset (it won\'t bind | | | to it in the PO formulation) | | | | | | Monitor BUN & Creatinine | | | (nephrotoxic) | +-----------------------------------+-----------------------------------+ | Patient Education | Do not take if allergy to any | | | PCNs | | | | | | Take with food or milk | | | | | | Notify provider if chest | | | feeding | | | | | | Notify provider of new rash, | | | dyspnea | | | | | | Notify provider of any watery, | | | malodorous diarrhea | | | | | | Complete the full course of | | | treatment | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | | **Aminoglycosides** | +===================================+===================================+ | | **Gentamicin** | +-----------------------------------+-----------------------------------+ | M/A | Inhibits protein synthesis of | | | bacteria, disrupts function, | | | replication processes, and cell | | | wall. | | | | | | **bactericidal**. They kill | | | bacteria by binding to the | | | bacterial 30S ribosomal subunit, | | | leading to misreading of mRNA and | | | production of faulty proteins, | | | which ultimately kills the | | | bacteria. Aminoglycosides, such | | | as gentamicin, amikacin, and | | | tobramycin, are particularly | | | effective against aerobic | | | gram-negative bacteria. | +-----------------------------------+-----------------------------------+ | Pharmacokinetics | Poor in GI tract Rapid via IM | | | or IV route | | | | | | Wide distribution, but | | | concentrates in the **[renal | | | tubules | | | (nephrotoxicity)]** | | | and the **[inner ear | | | (ototoxicity)]** | +-----------------------------------+-----------------------------------+ | Indication | Infections caused by aerobic, | | | Gram - bacteria | | | | | | Septicemia | | | | | | Respiratory tract infections | | | | | | Urinary tract infections | | | | | | Intra-abdominal infections | | | | | | Osteomyelitis | | | | | | Normally combination with | | | penicillin (because of high risk | | | of nephrotoxicity and | | | ototoxicity) -- penicillin makes | | | gentamicin more effective | | | (penicillin breaks down the cell | | | wall Gentamicin is more | | | accessible to their protein | | | synthesis (can\'t be mixed in the | | | same container because penicillin | | | will inactivate aminoglycosides | | | with direct contact) | +-----------------------------------+-----------------------------------+ | Contraindication | **Pregnancy** (risk of | | | congenital effects with the fetus | | | ex. deafness) | | | | | | Caution: | | | | | | - Pediatrics & Elderly -- they | | | are developing ears / | | | degradation of their ears and | | | kidneys | | | | | | - Renal impairment, use with | | | other nephrotoxic drugs | | | | | | - Neuromuscular disorders | +-----------------------------------+-----------------------------------+ | Adverse effect | Ototoxicity | | | | | | - **[Tinnitus]**, | | | hearing loss | | | | | | - Vertigo, dizziness | | | | | | Nephrotoxicity | | | | | | - Diminished **[urine | | | output]** | | | | | | - Fluid retention ( weight) | | | | | | Peripheral | | | **[neuropathy]** | | | | | | - Numbness, tingling | +-----------------------------------+-----------------------------------+ | Contraindication | **The 5 \"No\"s** | | | | | | **N**ephrotoxic/**O**totoxic | | | | | | No action on Gram + bacteria | | | | | | No protein synthesis in | | | bacteria | | | | | | No oral administration (IV, IM | | | only doesn\'t absorb in the gut) | | | | | | No in pregnancy (teratogenic) | +-----------------------------------+-----------------------------------+ | Nursing implications | Monitor serum | | | **[peak]** and | | | **[trough]** levels | | | | | | - Trough: lowest concentration | | | of medication / Measures | | | immediately before the next | | | dose | | | | | | - Peak: draw 30 mins after the | | | infusion has finished | | | | | | Administer penicillin **1 hour | | | apart** | +-----------------------------------+-----------------------------------+ | Patient Teaching | No PO formulary = Needs a | | | sharps container for home | | | | | | Notify provider if become | | | pregnant | | | | | | Notify/Monitor for adverse | | | effects and superinfections | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | | **Fluoroquinolones** | +===================================+===================================+ | | **Ciprofloxacin** | +-----------------------------------+-----------------------------------+ | M/A | Interferes with bacterial DNA | | | synthesis = | | | **[bactericidal]** | +-----------------------------------+-----------------------------------+ | Indication | Aerobic, Gram- bacteria | | | | | | First-line treatment for | | | Anthrax | | | | | | Multidrug-resistant TB | | | | | | (Not respond to Penicillin ) | | | Respiratory tract, UTI, GI, skin | | | infections | +-----------------------------------+-----------------------------------+ | Contraindication | Caution | | | | | | Hypersensitivity | | | | | | Use of tizanidine (muscle spasm | | | medication) | +-----------------------------------+-----------------------------------+ | Adverse effect & Nursing | **Rash (more likely develop | | implication | Stevens Johnson Syndrome)** Stop | | | the infusion: call MD | | | | | | Photosensitivity Sunscreen | | | | | | QT prolongation Monitor | | | **[telemetry]** & | | | review other medication | | | | | | N/V/D, abdominal pain | | | | | | Renal impairment Elevated liver | | | enzymes, BUN, creatinine | | | | | | **Achilles tendon rupture | | | *Assess for joint pain, redness, | | | weakness, sudden \"snap\"*** | | | | | | Crystalluria *Promote | | | hydration: **[2-3 | | | qt/day]*** | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | | **Tetracyclines** | +===================================+===================================+ | | Tetracycline | +-----------------------------------+-----------------------------------+ | M/A | Inhibits microbial protein | | | synthesis: bacteriostatic (**[not | | | bactericidal)]** | +-----------------------------------+-----------------------------------+ | Pharmacokinetics | Best taken on empty stomach | | | | | | Crosses placenta and enters | | | chest milk | +-----------------------------------+-----------------------------------+ | Note | Used for infections when | | | penicillin is contraindicated | | | (e.g. hypersensitivity) | +-----------------------------------+-----------------------------------+ | Indication | Rickettsia, Chlamydia | | | | | | Lyme disease | | | | | | Animal bites | | | | | | H. pylori | +-----------------------------------+-----------------------------------+ | Contraindication | Caution | | | | | | - Liver dysfunction | | | | | | - Older adults | | | | | | Hypersensitivity | | | | | | Pregnancy, Lactation | | | | | | Pediatrics: teeth | | | discoloration! | | | | | | Renal failure | +-----------------------------------+-----------------------------------+ | Adverse effects | CNS - Increased **[intracranial | | | pressure]** | | | | | | Bone - Permanent enamel | | | discoloration, Delayed bone | | | growth | | | | | | GI - N/V/D, **[epigastric | | | distress]**, | | | flatulence, esophagitis | | | | | | Skin - Rash, photosensitivity, | | | hyperpigmentation, **[black/furry | | | tongue]** | | | (accumulation of dead cells) | | | | | | Liver - Hepatotoxicity (rare) | | | | | | Superinfections - | | | Pseudomembranous colitis, | | | *Candida* infections | +-----------------------------------+-----------------------------------+ | Interactions | Drug-drug interaction | | | | | | Oral contraceptives (decreases | | | effectiveness) - Use alternate | | | **[birth control]** | | | methods | | | | | | Anticoagulants (enhances | | | Vitamin K effects) - Risk for | | | **[clotting]** | | | | | | Digoxin (increases absorption) | | | -- Monitor for digoxin toxicity | | | | | | Dairy, Antacids (decreases | | | tetracycline absorption) -- Take | | | 1 hour before or 2 hours after | | | meals | +-----------------------------------+-----------------------------------+ | Nursing implications & Patient | Take on an empty stomach | | teaching | | | | Sun protection! | | | | | | Use alternate contraception | | | | | | Schedule dairy and antacids | | | | | | Notify MD of watery, odorous | | | stools | | | | | | Don\'t give to children (teeth | | | discoloration) | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | | **Macrolides** | +===================================+===================================+ | | **Erythromycin** | +-----------------------------------+-----------------------------------+ | M/A | Inhibits protein synthesis, | | | leading to cell death | | | bactericidal | | | | | | **Macrolides** are **typically | | | bacteriostatic** as well, but | | | under certain conditions (e.g., | | | high concentrations or in rapidly | | | dividing bacteria), they may have | | | **bactericidal** effects. | +-----------------------------------+-----------------------------------+ | Pharmacokinetics | Absorption: small intestine | | | (oral) Improved with full glass | | | of water | | | | | | Distribution: Crosses placenta | | | and enters chest milk | | | | | | Elimination: **Bile** and urine | +-----------------------------------+-----------------------------------+ | Indication | Substitute for penicillin (Gram | | | -, esp. Group A Streptococci) | | | | | | Prophylaxis for newborns: | | | ophthalmic ointment (bacteria can | | | present in the birth canal) | | | | | | Legionnaire\'s disease (a | | | serious type of pneumonia caused | | | by the Legionella bacteria) | | | | | | Caution: Hepatic impairment | +-----------------------------------+-----------------------------------+ | Contraindication | Hypersensitivity to any | | | macrolide | | | | | | Chest feeding -- it will pass | | | into and disrupt the newborn\'s | | | bowel flora at risk of developing | | | a superinfection | | | | | | Concurrent meds that use CYP3A4 | | | for metabolism | +-----------------------------------+-----------------------------------+ | Adverse effect | CNS -- Confusion, | | | **[reversible]** | | | hearing loss, labile emotions | | | | | | Cardiac -- Ventricular | | | dysrhythmias (IV) | | | | | | GI -- N/V/D, cramping, | | | **anorexia** | | | | | | Allergy -- Rash, | | | **[bronchospasm]**, | | | anaphylaxis | | | | | | Liver -- Jaundice, | | | hepatotoxicity | | | | | | Superinfections -- | | | Pseudomembranous colitis | +-----------------------------------+-----------------------------------+ | Interactions | Drug-drug interactions | | | | | | Oral contraceptives (decreases | | | effectiveness) - Use alternate | | | **[birth control]** | | | methods | | | | | | CYP3A4 Inhibitors (Diltiazem, | | | fluconazole) -- Risk for | | | **[sudden cardiac | | | death]** (ventricular | | | dysrhythmias) | | | | | | Grapefruit juice (increases | | | erythromycin absorption) -- Avoid | | | | | | Dairy, Antacids, Alcohol | | | (decreases erythromycin | | | absorption) -- Take 1 hour before | | | or 2 hours after meals and avoid | | | alcohol | +-----------------------------------+-----------------------------------+ | Nursing implications & Patient | Take w/ full glass of water | | Teaching | | | | Avoid alcohol | | | | | | Assess hearing function | | | | | | Schedule diary, antacids | | | | | | Notify MD of watery, odorous | | | stools | | | | | | Assess for psychosocial effects | | | | | | Use alternate birth control | | | | | | Avoid grapefruit juice | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | | **Sulfonamides** | +===================================+===================================+ | | Trimethoprim-Sulfamethoxazole | | | (TMP-SMX) - Bactrim | +-----------------------------------+-----------------------------------+ | M/A | Inhibit folic acid production | | | which stops the ability for | | | bacteria to multiply: | | | Bacteriostatic -- **not** | | | bactericidal! | | | | | | It doesn\'t kill what is | | | already there while preventing it | | | from getting any larger as an | | | infection | +-----------------------------------+-----------------------------------+ | Pharmacokinetics | Crosses placenta and | | | blood-brain barrier | | | | | | Enters chest milk (small | | | amounts) | +-----------------------------------+-----------------------------------+ | Indications | Severe UTIs | | | | | | P. jirovecii pneumonitis | | | | | | Shigella enteritis | | | | | | Salmonella | | | | | | Pseudomonas | +-----------------------------------+-----------------------------------+ | Contraindication | Sulfa allergy | | | | | | Hypersensitivity to salicylates | | | (Aspirin) | | | | | | Pediatrics \< 2 months old | | | hyperbilirubinemia liver failure | | | and severe hepatotoxicity | | | | | | Pregnancy | | | | | | Caution | | | | | | - Liver impairment | | | | | | - Renal impairment | | | | | | - Hypoaldosteronism | | | | | | - Conditions or medications | | | which can cause hyperkalemia | | | | | | - Drugs which cause | | | nephrotoxicity | | | | | | **Trimethoprim**, one of the | | | components of TMP-SMX, has a | | | **potassium-sparing** effect, | | | which can inhibit the secretion | | | of potassium by the kidneys. This | | | effect can lead to an increase in | | | potassium levels in the blood. | | | | | | In patients with | | | hypoaldosteronism, the body\'s | | | ability to regulate potassium is | | | already impaired because of low | | | levels of **aldosterone**, a | | | hormone that helps balance sodium | | | and potassium in the kidneys. | | | Aldosterone normally promotes the | | | excretion of potassium. With low | | | aldosterone, potassium retention | | | is increased, and using TMP-SMX | | | could exacerbate this, leading to | | | potentially dangerous levels of | | | potassium (hyperkalemia). | +-----------------------------------+-----------------------------------+ | Adverse effect | GI - Abd pain, N/V/D, anorexia, | | | pancreatitis | | | | | | Hematologic - Hyperkalemia, | | | hypoglycemia, anemia, leukopenia, | | | thrombocytopenia | | | | | | Derm - Rash, | | | **[SJS]**, urticaria, | | | photosensitivity | | | | | | Hypersensitivity - Dyspnea, | | | shortness of breath | | | | | | Renal - Increased BUN & | | | Creatinine, renal failure, | | | interstitial nephritis | | | | | | CNS -- Kernicterus (brain | | | damage from hyperbilirubinemia, | | | hepatotoxicity) in children \< 2 | | | months | +-----------------------------------+-----------------------------------+ | Patient Education | Take with full glass of water | | | | | | Prevent interstitial nephritis | | | by hydrating: 2-3L per day | | | | | | Monitor for superinfection | | | | | | Use alternative birth control | | | methods | | | | | | If diabetic, monitor for | | | hypoglycemia | | | | | | Use sun protection | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | | Vancomycin | +===================================+===================================+ | M/A | Inhibits cell wall synthesis | | | bactericidal | +-----------------------------------+-----------------------------------+ | Indication | Only effective against Gram + | | | bacteria | | | | | | MRSA | | | | | | *C. difficile* | +-----------------------------------+-----------------------------------+ | Contraindications | VRE: Vancomycin-resistant | | | enterococci | | | | | | Renal failure | +-----------------------------------+-----------------------------------+ | Special Consideration | Toxicity - **Nephrotoxic**: | | | monitor BUN & creatinine | | | | | | Labs - Monitor serum **trough** | | | levels: narrow index | | | | | | IV administration - Must occur | | | over at least 1 hour to prevent | | | **Vancomycin Flushing Syndrome** | | | (face, neck, chest) | | | | | | IV Site - **Vesicant**: monitor | | | IV site for phlebitis (NO hand | | | IV) | +-----------------------------------+-----------------------------------+