Clinical Antimicrobial Drug Therapy PDF

Clinical Antimicrobial Drug Therapy Robert Goggs Associate Professor, E/CC [email protected] PollEv.com/robertgoggs388 Or text ROBERTGOGGS388 to 22333 to join the session, then text your responses. URINARY TRACT INFECTIONS  Learning Objectives 1. Suggest antimicrobial drug treatment...

Clinical Antimicrobial Drug Therapy Robert Goggs Associate Professor, E/CC [email protected] PollEv.com/robertgoggs388 Or text ROBERTGOGGS388 to 22333 to join the session, then text your responses. URINARY TRACT INFECTIONS  Learning Objectives 1. Suggest antimicrobial drug treatment strategies for common infectious diseases affecting the skin, respiratory system and urinary tract of small animals 2. Understand how disease severity impacts antimicrobial drug prescribing practices 3. Know what consensus guidelines exist for management of infectious diseases affecting the skin, respiratory system and urinary tract of small animals *Note: Learning objectives generally describe the minimum knowledge needed to pass the course.  eclinpath.com Sporadic bacterial cystitis Excludes: Comorbidities e.g. endocrinopathies ≥3 episodes per year Clinical signs: Dysuria Pollakiuria Stranguria Hematuria Dx: Clinical evaluation + Urine cytology + Bacterial culture Sporadic bacterial cystitis Clinical signs are a result of inflammation Analgesia alone may be as effective as antimicrobials in uncomplicated cases Prescribe analgesia in all cases regardless of whether antimicrobials are used Consider prescribing analgesia (NSAIDs in dogs, buprenorphine in cats) Consider adding antimicrobials 3-4 days later if clinical signs persist or worsen Antimicrobials also reasonable in dogs while awaiting culture / susceptibility In cats, withholding antimicrobials pending urine culture is reasonable Sporadic bacterial cystitis First-line choices: Amoxicillin or Amoxicillin/Clavulanate Trimethoprim-sulfonamide Recommended duration of therapy is 3-5d Reserved for cases with resistant organisms: Nitrofurantoin Fluoroquinolones 3rd generation cephalosporins Use local antibiograms to guide empirical choices You must try to differentiate clinical need from convenience Follow-up Clinical response is expected within 48h Lack of clinical response within 48 h should prompt further investigation If initial culture results indicate resistance to empirical drug choice... Has the patient responded to your empiric drug choice...? If yes, do nothing If no, then change drug based on the C/S results Empirically changing antimicrobials in reaction to poor response is bad medicine Re-examine all animals with partial or complete clinical failure to treatment Consider all of the possible reasons for “treatment failure” Recurrent UTI ≥2 episodes in 6 months OR ≥3 episodes in 12 months May result from relapsing or persistent infection, or from reinfection Consider which of these is most likely to plan diagnostics Recurrent UTI Don’t prescribe more antimicrobials without exploring potential underlying causes Urine culture of cystocentesis sample If new pathogen is different from previous organisms then reinfection is likely Identify address any predisposing factors Make certain antimicrobial is achieving adequate urine concentrations Drug choice Drug dose Dosing regimen Antimicrobial susceptibility pattern of the isolate Client compliance Pyelonephritis Infection of renal parenchyma resulting from ascending infection or bacteremia Tissue concentration of antimicrobials is key determinant of efficacy You must use serum or tissue breakpoints not urine breakpoints Enterobacteriales cause majority of cases Uncomplicated: No underlying comorbidity Complicated: Comorbidities like DM, neoplasia, nephrolithiasis, ectopic ureters Clinical signs are vague Definitive diagnosis is difficult Can result in severe and rapid kidney injury Pyelonephritis Initiate treatment immediately - do not wait for C/S results Give antimicrobials intravenously if patient is sick Initial drug choice should have known efficacy against Enterobacteriaceae Consider your local antibiograms, if available If not, look at national antibiograms Use serum/tissue breakpoints Fluoroquinolones e.g. enrofloxacin are first choice agents 3rd generation cephalosporins e.g. cefotaxime, ceftazidime also acceptable Pyelonephritis Treat for 10-14 days, then recheck 1-2 weeks after antimicrobials discontinued Physical examination Serum BUN & creatinine Urinalysis Aerobic bacterial urine culture If clinically improved but bacteria still present then... Is this subclinical bacteriuria? (see guidelines) Are there reasons for potential bacterial persistence: AMR Urolithiasis Anatomic defects Comorbidities RESPIRATORY TRACT INFECTIONS Canine infectious respiratory disease complex Acute onset cough Sneezing Nasal and ocular discharges Fever (uncommon) Causal agents (viruses) Causal agents (bacteria) Adenovirus-2 Bordetella bronchiseptica Distemper virus Strep. equi zooepidemicus Respiratory coronavirus Mycoplasma spp. Influenza viruses Herpesvirus Pneumovirus Parainfluenza virus Canine infectious respiratory disease complex Antimicrobial therapy often not indicated Most cases are due to viral infections Most CIRDC cases resolve spontaneously within 10d Consider antimicrobials in first 10d if: Fever Lethargy Anorexia Mucopurulent nasal discharge First choice: Doxycycline Other (perhaps less ideal) options: Amoxicillin, Amoxicillin/Clavulanate Tx for 7-10d Pneumonia Community acquired pneumonia Bordetella bronchiseptica Mycoplasma spp. Streptococcus equi zooepidemicus Streptococcus canis Secondary pneumonia Secondary pneumonia organisms: Viral infections E. coli Aspiration Pasteurella spp. Peri-anesthesia Streptococcus spp. Inhalation of foreign bodies B. bronchiseptica Immunodeficiency syndromes Enterococcus spp. Neoplasia Mycoplasma spp. Ciliary dyskinesia S. pseudintermedius Bronchiectasis Pseudomonas spp. Collapsing airway Pneumonia Provide empirical antimicrobial treatment while waiting for test results De-escalate treatment based on antimicrobial susceptibility testing Parenteral antimicrobial treatment while hospitalized, oral after discharge Drug choices are based on nature and severity of pneumonia Community acquired Aspiration pneumonia Pneumonia with sepsis Recommended duration is 4-6 weeks, but this is likely grossly excessive Pneumonia case 1: 10 week old F Shar-Pei puppy Adopted from Patrick’s Puppies on February 1st Seen at primary care DVM February 4th for routine DHPPiL vaccinations Presented to you on February 6th for acute onset coughing BAR, prolonged skin tent T 102.1 °F HR 135 bpm RR 30 rpm Paroxysmal wet cough Lung sounds harsh in all fields Clear nasal discharge Pulse oximetry (SpO2) 98%  Pneumonia case 1 What drug(s) would you choose? Patient stable Most likely community acquired: Doxycycline recommended 1st choice empirical Rx Azithromycin sometimes used empirically Amoxicillin ± Clavulanate also an option Pneumonia case 2: 2y MN Bulldog Increased respiratory rate and effort, lethargy 2d ago, vomited x3 Yesterday sounded congested Didn’t want to walk very far No coughing or sneezing No prior medical Hx BAR T 101.7 °F HR 100 bpm RR 40 rpm Paroxysmal wet cough Lung sounds harsh in all fields Pneumonia case 2 Pneumonia case 2 Patient stable Aspiration pneumonia: Ampicillin Ampicillin-sulbactam Cefazolin Pneumonia case 3: 2.5y FS Gt. Dane Owners returned home to find vomit in crate Dog went outside, vomited x2, refused to come in Dog vomited in the car Suspected to have ingested a sock Currently up to date on vaccines Presents to you in respiratory distress PCV 42% / TS 6.2 g/dL Recumbent, non-ambulatory BG 56 mg/dL LO T: 104.1°F Azo 15-26 mg/dL HR: 152bpm Lactate 6.0 mmol/L HI RR: 90 rpm with increased effort Leukocytes (6,200/µL) LO MMb: Pink, CRT 1s Neutrophils (2,600/µL) LO Harsh lung sounds Band neutrophils (2,300/µL) HI Pneumonia case 3 Pneumonia case 3 Patient unstable Sepsis due to pneumonia: Enrofloxacin or Marbofloxacin + Ampicillin or Ampicillin/Sulbactam or Clindamycin PYODERMA  Beco L et al. Vet Rec. 2013; 172:72-8. Pyoderma: Myriad presentations Intertrigo Bullous impetigo Bacterial overgrowth syndrome Superficial folliculitis Superficial spreading pyoderma  Beco L et al. Vet Rec. 2013; 172:72-8. Pyoderma: Myriad presentations Pyotraumatic dermatitis Interdigital furunculosis Feline chin acne Mucocutaneous pyoderma GSD pyoderma Deep pyoderma  Beco L et al. Vet Rec. 2013; 172:72-8. Pyoderma: Diagnosis Systemic or topical therapy? Superficial folliculitis Is the infection mild, superficial or focal? Topical antimicrobial shampoos and sprays Topical antibiotics if topical antiseptics do not clear the infection Topical antiseptic treatments can hasten clearing the infection Is the infection deep, severe or generalized? Systemic antimicrobials might be appropriate Deep pyoderma Some factors to consider Coagulase positive Staphylococcus spp. is most common cause Staphylococcus pseudintermedius Antimicrobial susceptibility of Staph. pseudintermedius varies % MDR and % MRSP isolates have increased over time Most cases of canine pyoderma are secondary to other pathologies Skin is the largest organ of the body but blood supply is comparatively poor Length of treatment will depend on the depth of the infection Combining systemic therapy with topical antiseptic treatment hastens cure Evidence-based veterinary medicine Good evidence for high efficacy: Superficial pyoderma: SC Cefovecin Deep pyoderma: PO Amoxicillin/Clavulanate Evidence-based veterinary medicine Fair evidence for moderate-high efficacy: Superficial pyoderma: PO Amoxicillin/Clavulanate PO Cefadroxil PO Clindamycin PO Cotrimoxazole PO Sulfadimethoxine-Ormetoprim Deep pyoderma: PO Cefadroxil PO Pradofloxacin SC Cefovecin First-line antimicrobial drug choices Amoxicillin/Clavulanate Cefadroxil Cephalexin Clindamycin Lincomycin If administration may be difficult, and/or compliance is likely to be poor Cefpodoxime (Palatable once daily) Cefovecin (Single injection) Second-line antimicrobial drug choices Not appropriate for empirical antibiotic treatment Only when C/S evidence indicates first-line drugs will not be effective Cefovecin Cefpodoxime Clindamycin / Lincomycin Third-line Chloramphenicol Fluoroquinolones Rifampin Aminoglycosides Duration of therapy Depends on the depth of the infection Superficial pyoderma: 2-3 weeks Deep pyoderma: Improve within 2 weeks, resolution can take 4-6 weeks Continue treatment until... Infection is visually and palpably cured AND cytology is normal Tx for 7d post resolution for superficial infections, 14d for deep pyoderma Pyoderma case example 8-year-old, FS, mixed breed dog, 38kg September received cephalexin 750mg PO BID x 21 days Skin lesions did not resolve October received cephalexin 1000mg PO BID x 14 days Skin lesions mostly resolved Worsened 3-5 days after stopping antimicrobials January received cephalexin 1000mg PO BID x 21 days Skin lesions resolved completely But... it’s now early February and the lesions are back, and the clients are cranky Not responding to antibiotics – Now what? If at first, you don’t succeed… You probably missed something! Get a thorough history Do more diagnostic testing Cytology Culture and Susceptibility Screen for endocrinopathies Skin biopsies Refer them? DO NOT... Do the same thing over and over again... And expect different results  1 Mick - 293407 Canine German Short-Haired Pointer Male Skin Aerobic Culture Result Few Staphylococcu Comments: A methicillin-resistant Staphylococcus species was isolated. B oxacillin, other members of the beta-lactam class are therefore interpreted a Staphylococcus pseudintermedius Culture and susceptibility AMIKACIN NO INTERP ( 8 ) AUGMENTIN RESISTANT ( 4 ) CEFAZOLIN RESISTANT ( 8 ) CEFPODOXIME RESISTANT ( >8 ) Chloramphenicol? CEPHALOTHIN RESISTANT ( 4 ) Can you use rifampin? DOXYCYCLINE RESISTANT ( >0.5 ) ENROFLOXACIN RESISTANT ( >4 ) ERYTHROMYCIN RESISTANT ( >4 ) Cornell University GENTAMICIN INTERMEDIATE ( 8 ) IMIPENEM Animal Health Diagnostic Center RESISTANT ( 4 ) MINOCYCLINE RESISTANT ( >2 ) NITROFURANTOIN SUSCEPTIBLE ( 2 ) Male PENICILLIN RESISTANT ( >8 ) Skin PRADOFLOXACIN RESISTANT ( >2 ) Staphylococcus pseudintermedius RIFAMPIN SUSCEPTIBLE ( 1 ) TRIM/SULFA RESISTANT ( >4 ) Report Generation Date: 9/24/2020 2:04:34PM Finalized Re This report including all attachments is for the sole use of the intended recipients and Any unauthorized review, use, disclosure, alteration or distribution is strictly prohibited. If all copies Test of the original report. Interpretations Antimicrobial Susceptibility (MIC)  1 Mick - 293407 Canine German Short-Haired Pointer Male Skin Aerobic Culture Result Few Staphylococcu Comments: A methicillin-resistant Staphylococcus species was isolated. B oxacillin, other members of the beta-lactam class are therefore interpreted a Staphylococcus pseudintermedius Culture and susceptibility AMIKACIN NO INTERP ( 8 ) AUGMENTIN RESISTANT ( 4 ) CEFAZOLIN RESISTANT ( 8 ) CEFPODOXIME RESISTANT ( >8 ) Nitrofurantoin will not be effective CEPHALOTHIN RESISTANT ( 4 ) DOXYCYCLINE RESISTANT ( >0.5 ) You could consider chloramphenicol ENROFLOXACIN RESISTANT ( >4 ) Watch out for liver and BM toxicity ERYTHROMYCIN RESISTANT ( >4 ) Cornell University GENTAMICIN INTERMEDIATE ( 8 ) IMIPENEM Animal Health Diagnostic Center RESISTANT ( 4 ) Make certain this is a bacterial infection MINOCYCLINE RESISTANT ( >2 ) NITROFURANTOIN SUSCEPTIBLE ( 2 ) Male Use aggressive topical management Skin PENICILLIN PRADOFLOXACIN RESISTANT ( >8 ) RESISTANT ( >2 ) Staphylococcus pseudintermedius 4% chlorhexidine RIFAMPIN SUSCEPTIBLE ( 1 ) Vetericyn (HOCl) TRIM/SULFA RESISTANT ( >4 ) Report Generation Date: 9/24/2020 2:04:34PM Finalized Re This report including all attachments is for the sole use of the intended recipients and Any unauthorized review, use, disclosure, alteration or distribution is strictly prohibited. If all copies Test of the original report. Interpretations Antimicrobial Susceptibility (MIC) Thank you for participating in today’s session