Antibiotics For GBS, UTI, & BV PDF

ANTIBIOTICS FOR GBS, UTI, & BV Readings: Ch 16, 17, & 20 in Pharmacology Revealed 1 ©Dr. E. Cates 2023 AGENDA • Review from last week • Intrapartum antibiotic prophylaxis of GBS • Antibiotic treatment of urinary tract infections • Antibiotic treatment of bacterial vaginosis • Infographic Sharing...

ANTIBIOTICS FOR GBS, UTI, & BV Readings: Ch 16, 17, & 20 in Pharmacology Revealed 1 ©Dr. E. Cates 2023 AGENDA • Review from last week • Intrapartum antibiotic prophylaxis of GBS • Antibiotic treatment of urinary tract infections • Antibiotic treatment of bacterial vaginosis • Infographic Sharing Presentations 2 ©Dr. E. Cates 2023 LAST TIME, ON PHARMACOTHERAPY… • • • • 884/93 Selecting Antibiotic Treatment Microbial Anatomy Function of Antibiotics • • • • Cell wall synthesis inhibitors Protein synthesis inhibitors DNA synthesis inhibitors Folate synthesis inhibitors • Acquisition and mechanisms of antibiotic resistance • Antibiotic Treatment of Mastitis • APNO 4 ©Dr. E. Cates 2023 IAP OF EOGBSD • GBS – Streptococcus agalactiae, Gram+, aerobic diplococci • A significant cause of neonatal morbidity and mortality in North America • Pneumonia, meningitis, sepsis, death • This is the currently the only situation where IV antibiotics are legislated for use by midwives • Midwives may administer the following for GBS on their own authority: • • • • • Penicillin G Ampicillin Cefazolin Clindamycin Erythromycin • See “Additional Resources” on A2L for the CPGs that guide our practice on this topic • AOM CPG #19: Antepartum, Intrapartum and Postpartum Management of GROUP B STREPTOCOCCUS • SOGC CPG #298: The Prevention of Early-Onset Neonatal Group B Streptococcal Disease • ACOG committee Opinion #797 • CDC Guideline & algorithm of 2010 has been replaced by the ACOG guideline: • Group B Strep Prevention Guidelines | CDC 6 ©Dr. E. Cates 2023 NEONATAL GBS PROPHYLAXIS • The prevention of neonatal GBS infection centers on the administration of antibiotics to the pregnant person • As the organism of interest is a Gram+ streptococcus, the first line of treatment will be Penicillin G or Ampicillin • Current clinical guidelines favour Pen G over Ampicillin due to narrower spectrum • If there is evidence of an allergy, or intolerance to penicillins, cefazolin can be used • If the person has a history of immediate, serious betalactam sensitivities (immediate hives, anaphylaxis) then use clindamycin (if the strain is both clindamycin and erythromycin sensitive Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 7 HISTORY TAKING: PENICILLIN ALLERGY CPG-Group B Streptcoccous-PUB.pdf (ontariomidwives.ca) 8 ©Dr. E. Cates 2023 SOGC CPG #298 THE PREVENTION OF EARLY-ONSET NEONATAL GBS DISEASE Recommendations: 1. Offer all women screening for group B streptococcus disease at 35 to 37 weeks’ gestation with culture done from one swab first to the vagina then to the rectal area 2. Treat the following women intrapartum at time of labour or rupture of membranes with IV antibiotics: 1. 2. 3. all women positive by GBS culture screening done at 35 to 37 weeks any women with an infant previously infected with GBS any women with documented GBS bacteriuria (regardless of level of colony-forming units per mL) in this pregnancy Recommended antibiotic regimens for intrapartum prophylaxis: 1. Penicillin G 5 million units IV, then 2.5 to 3.0 million every 4 hours until delivery or 2. If the woman is allergic to penicillin but has a low risk of anaphylaxis: cefazolin 2g IV then 1g every 8 hours until delivery or 3. If the woman is allergic to penicillin and at risk of anaphylaxis: clindamycin 900 mg IV every 8 hours until delivery (if isolate is susceptible to clindamycin with no inducible resistance) or vancomycin 1g IV every 12 hours until delivery 9 ©Dr. E. Cates 2023 AOM CPG #19 (REPLACES #11&#16) ANTEPARTUM, INTRAPARTUM AND POSTPARTUM MANAGEMENT OF GROUP B STREPTOCOCCUS • Similar to the SOGC guideline in terms of treatment, but grounded in the tenants of informed choice and offers expectant management and treating on risk factors as options If a client chooses to treat in labour, recommended antibiotic regime for IAP as recommended by the CDC: I. Penicillin G 5 million units IV initial dose, followed by 2.5 million units IV every 4 hours until delivery. OR II. If the client is penicillin-allergic but at low risk for anaphylaxis, then cefazolin 2g IV initial dose, followed by 1g every 8 hours until delivery. OR III. If the client is penicillin allergic and at risk of anaphylaxis, then clindamycin 900 mg IV every 8 hours until delivery (IF the isolate is susceptible to clindamycin with no inducible resistance) OR vancomycin 1g IV q12h until delivery 10 ©Dr. E. Cates 2023 CONSIDERATIONS WHEN USING VANCOMYCIN • Vancomycin is indicated for GBS IAP in the rare event of the client having an anaphylactic penicillin allergy AND tests positive for a GBS strain that is resistant to both clindamycin and erythromycin • If vancomycin is the only IAP option, clients should be informed that: • Vancomycin must be administered intravenously in a dilute solution by intermittent infusion over a period of no less than 60 minutes (at a rate of no more than 10 mg/min), by IV pump. • Exaggerated hypotension, including shock, and rarely cardiac arrest, may result from rapid bolus administration of vancomycin. • Vancomycin is irritating to tissue and causes drug fever, pain and possibly necrosis if injected intramuscularly. • Due to the controlled conditions under which vancomycin is administered, home birth is not a feasible option. • Vancomycin is not currently on the 884/93. Midwives needing vancomycin must consult with a physician for a medication order. 11 ©Dr. E. Cates 2023 GBS PROPHYLAXIS PENICILLINS Excretion of Penicillins • Primary route is renal • Tubular secretion and glomerular filtration both occur • Much of the penicillin ends up in the urine unchanged • Any change in kidney function will lead to a big change in the t1/2 of the drug • E.g., the t1/2 of PenG will go from 1h-10h in people with impaired renal function • The dependency on renal excretion keeps the concentration of the penicillin in the newborn relatively high, as their renal function is poor • t1/2 in the newborn >3h Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 12 GBS PROPHYLAXIS PENICILLINS Adverse Effects of Penicillins • Penicillins have remarkably little direct, serious toxicity compared to other antibiotics • Hypersensitivity is the greatest, single side-effect of the penicillins • 0.7-4% of users will show hypersensitivity • Rash is the most common hypersensitivity found, but serious side-effects include angioedema, hives, respiratory issues, hypotension • Diarrhea may occur due to the disruption of the normal gut flora – this is not typical with the acute exposure for GBS prophylaxis Drug Interactions • No drugs on the 884/93 which have significant interactions Contraindications • Prior history of hypersensitivity to the penicillins or cephalosporins is the most common contraindication Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 13 GBS PROPHYLAXIS CEPHALOSPORINS Cefazolin • A beta-lactam antibiotic, but is acceptable if the client only has mild hypersensitivity to penicillins • 1% risk of the clinically-significant allergic cross-reaction between the penicillins and the cephalosporins though perhaps 20% of the penicillin-allergic patients show some immune response • A first-generation cephalosporin with a moderately broad spectrum • t1/2 = 2h, which is longer than other 1st generation cephalosproins, so the frequency of dosing is less • Like the penicillins, tubular secretion and glomerular filtration of the drug means much cephazolin ends up in the urine unchanged • Any change in renal function will impact the t1/2 of the drug Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 14 GBS PROPHYLAXIS CEPHALOSPORINS Adverse Effects of Cefazolin • Hypersensitivity is the single greatest adverse effect • appears to be identical in frequency and etiology to the penicillins • Diarrhea may occur due to disruption of the gut flora, but this adverse effect usually requires a full, long-term course of cefazolin Drug Interactions with Cefazolin • Few interactions of cefazolin with other drugs, none on the 884/93 • Drug interactions unlikely with acute exposure for GBS prophylaxis Contraindications of Cefazolin • History of immediate, severe, hypersensitivity reaction to a penicillin or cephalosporin 15 Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 GBS PROPHYLAXIS – CLINDAMYCIN & ERYTHROMYCIN • If the person has a history of serious, immediate β-lactam hypersensitivities (hives, anaphylaxis) then clindamycin and erythromycin are acceptable choices since these antibiotics do not have a β-lactam group • These are antibiotics which inhibit protein synthesis by binding with the microbial ribosome and they have a narrow spectrum of action • Both interfere with the 50S ribosomal subunit • There is significant bacterial resistance to erythromycin (7-25%) and clindamycin (3-15%) • The CDC (2010) recommends against the use of erythromycin for GBS prophylaxis due to widespread antibiotic resistance • There is typically a cross-resistance between clindamycin and erythromycin so there is usually little point switching between the two antibiotics 16 ©Dr. E. Cates 2023 Slide Modified From: Dr. C. Beites, Laurentian University GBS PROPHYLAXIS – CLINDAMYCIN Metabolism and Excretion of Clindamycin • Occurs in the liver, but some drug is excreted unchanged in the urine • Amount secreted in the urine is not enough to treat a UTI Adverse Effects of Clindamycin • Diarrhea may occur after the use of clindamycin due to disruption of the gut flora • Colitis typically takes a full-course of clindamycin exposure, but has been seen with GBS prophylaxis • Bacterial overgrowth, particularly when it is in association with Clostridium difficile, may result in pseudomembranous colitis Drug Interactions with Clindamycin • Few drug interactions • Will antagonize the effects of erythromycin, so the 2 should not be given together • No interactions with any of the drugs on the 884/93 17 Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 URINARY TRACT INFECTIONS (UTIs) • Relatively common in pregnancy (up to 10%) • Approximately 80% of UTIs are caused by E. coli • Other causative agents: • Streptococci (including GBS) • Staphylococci (e.g., S. epidermidis and S. saprophyticus) • Enterococci 19 ©Dr. E. Cates 2023 UTIs • Female anatomy increases risk of UTI over male anatomy because: • Shorter length of the female urethra allows easier access by bacteria to the bladder • Warm moist vulva and the rectum are in close proximity • Prevalence increased in pregnancy: • Significant urethral dilation leading to urinary stasis in 2nd and 3rd trimesters • Relaxing effects of progesterone and mechanical compressions of ureters by the uterus at the pelvic brim lead to an incomplete emptying of the bladder 20 ©Dr. E. Cates 2023 Slide Modified From: C. Osepchook, Ryerson University UTIs • UTIs in pregnancy should be treated whether or not they are symptomatic because: • • • • Can lead to PPROM Premature labour & birth Associated with pyelonephritis Associated with chorioamnionitis • Appropriate treatment of UTIs in pregnancy depends somewhat on the stage of fetal development • E.g., avoid ciprofloxacin, sulfamethoxazole, and trimethoprim in the 1st trimester because of potential teratogenicity 21 ©Dr. E. Cates 2023 TREATING UTIs • Midwives currently have the following drugs at their disposal for the treatment of UTIs • Nitrofurantoin • Reactive metabolites have many damaging effects on cells • • • • • Damage to bacterial DNA Inhibit protein synthesis Inhibit RNA synthesis Inhibit cell-wall synthesis Inhibit aerobic metabolism • Sulfamethoxazole-Trimethoprim • Folate synthesis inhibitor • Trimethoprim • Folate synthesis inhibitor • Ciprofloxacin • DNA synthesis inhibitor ©Dr. E. Cates 2023 22 NITROFURANTOIN • A pro-drug • Reduced by microbial metabolism into a number of reactive intermediates • damage several bacterial components, including deoxyribonucleic acid (DNA) • Bacteria are more capable of reducing the nitrofurantoin to the active metabolites than mammals • Hardly metabolized in liver but rapidly excreted in urine • t1/2 is 0.3-1 hr • MACROBID is extended-release form of regular nitrofurantoin and is given every 12 hours • The urine is coloured brown by the drug 23 ©Dr. E. Cates 2023 NITROFURANTOIN Side-Effects and Contraindications: • According to Motherisk : meta-analysis failed to show teratogenic risk in early gestation • Anorexia, nausea, vomiting, and diarrhea (about 10%) • Skin rashes are common • Never give this drug after 36 weeks because of possibility of generating a hemolytic anemia of the newborn especially in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency (Mediterranean pop, African) • Probably best choice in early-mid pregnancy • Safe during lactation Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 24 CIPROFLOXACIN • DNA synthesis inhibitor • Partially metabolized and excreted in the feces but 30-50% excreted into the urine unchanged • t1/2 is 3-5h • Unrelated to penicillins so useful in penicillin-allergic clients Side-Effects and Contraindications • Nausea, vomiting, diarrhea • Rash in 1% • Avoid in first trimester due to teratogenicity: because of distribution (well absorbed in bone) can have effects on growing cartilage of fetus leading to arthropathies Drug Interactions • Inhibited by cations • Mg+2, Al+3, Fe+2 are all regularly consumed by pregnant people ©Dr. E. Cates 2023 25 SULFAMETHOXAZOLETRIMETHOPRIM • Folate synthesis inhibitor as it crosses the placenta • Use later in gestation • Avoid in the first trimester • Anencephaly, choanal atresia, herniated diaphragm, heart hypoplasia • If must be used in first trimester, folic acid supplementation is suggested • Avoid after 32 weeks and at term • Why? A. Sulfa drugs bind serum albumin in circulation half-life of 9-12 hours B. Can cross placenta and enter fetal tissues C. Sulfamethoxazole displaces bilirubin from binding sites on albumin -jaundice D. Bilirubin excess—> goes to brain kernicterus (brain damage) Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 26 SULFAMETHOXAZOLETRIMETHOPRIM Adverse Effects of Sulfamethoxazole: • Never give sulfamethoxazole at term because, like nitrofurantoin, there is the possibility of generating a hemolytic anemia in the newborn • Nitrofurantoin and sulfamethoxazole both may cause hemolysis in patients or fetuses with glucose-6-phosphate dehydrogenase (G6PD) deficiency • Crystalluria • Sulfamethoxazole can be acetylated and form crystals at a low pH – such of that of urine, leading to crystalluria • Maintain good hydration and do not give the drug to people with compromised renal function 27 ©Dr. E. Cates 2023 SULFAMETHOXAZOLETRIMETHOPRIM Adverse Effects of Sulfamethoxazole: • Sulfa drug allergy is found in about 3% of the population and an itchy skin rash is the most common symptom of the allergy • Stevens-Johnson syndrome and toxic epidermal necrolysis are rare complications • Photosensitivity • Broad spectrum, increased risk of superinfection • An antifolate drug – folic acid required for blood cell production • pathological conditions of the blood may occur, particularly megaloblastic anemia, leukopenia, and granulocytopenia, may occasionally occur 28 ©Dr. E. Cates 2023 SULFAMETHOXAZOLETRIMETHOPRIM Drug Interactions with Sulfamethoxazole • Few drug interactions and none on the 884/93 • MW cannot currently prescribe sulfamethoxazole on its own for UTIs • Many organisms that cause UTIs are resistant (either fully or in part) to sulfa drugs • Sulfamethoxazole-Trimethoprim is a common prescription for the UTI • Trimethoprim can be administered alone, especially in cases of sulfa allergy Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 29 TRIMETHOPRIM • Trimethoprim monotherapy can currently be expected to treat 80-90% of uncomplicated UTIs • Bacterial resistance, particularly in E. coli, is common • Category C, folate synthesis inhibitor, avoid in 1st trimester • Very lipid soluble, absorbed readily, excreted rapidly • 60-80% excreted unchanged into the urine • Partially metabolized by CYP2C9 and CYP3A4 Adverse Effects of Trimethoprim • Generally, well tolerated • Hypersensitivity • Because trimethoprim is an antifolate drug, blood dyscrasias, particularly megaloblastic anemia, leukopenia, and granulocytopenia may occasionally occur Drug Interactions • Inhibits some CYP enzymes • Few drug interactions and none on the 884/93 Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 30 ABNORMAL VAGINAL SECRETIONS • Either due to imbalance of the microflora or infection • 3 most common causes: 1. Bacterial Vaginosis (BV) • prokaryotic 2. Vulvovaginal candidiasis • Yeast, eukaryotic 3. Trichomonas vaginalis • Protozoa, eukaryotic Image Sourced From: http://www.tasiaaudre.com Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 32 BACTERIAL VAGINOSIS • Most common cause of vaginal discharge • Characterized by overgrowth of genital tract organisms • Usually Gardnerella (Gram variable coccobacillic anaerobe) • Mobiluncus spp. • Other anaerobic bacteria with a depletion of lactobacilli BV during pregnancy is associated with: • Premature rupture of membranes • Chorioamnionitis • Preterm labour & birth • Post-cesarean delivery endometritis J Obstet Gynaecol Can 2008;30(8):702–708 Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 33 ABNORMAL VAGINAL SECRETIONS Vulvovaginal Candidiasis Trichomoniasis • Approximately 90% of cases caused by Candida albicans • Sexually transmitted infection • Remainder caused by other Candida spp. • • • • C. glabrata C. parapsilosis C. tropicalis S. cerevisiae • Recommended treatment in pregnancy = OTC treatments • Caused by the protozoan Trichomonas vaginalis • Usually treated with metronidazole – although there is some drug resistance among protozoans • Not an infection that is currently within the midwifery scope to treat • Longest possible course • E.g., MONISTAT 7d 34 ©Dr. E. Cates 2023 Slide Modified From: Dr. C. Beites, Laurentian University ABNORMAL VAGINAL SECRETIONS 35 ©Dr. E. Cates 2023 Slide Modified From: Dr. C. Beites, Laurentian University BACTERIAL VAGINOSIS • Recommended treatment: 1. Metronidazole 500mg PO, bid for 7d 2. Clindamycin 300mg PO, bid for 7d • Both of these treatments are on the 884/93 • Recurrence rates are high (up to 1/3) • Reconfirm Dx before embarking on multiple courses of therapy • Extending Rx to 10-14d has been shown to be an effective Rx strategy with multiple, documented, repeated recurrences J Obstet Gynaecol Can 2015;37(3):266-274 36 ©Dr. E. Cates 2023 Metronidazole (FLAGYL) • A pro-drug Mechanism • Reduced by the Electron Transport Chain in some anaerobic bacteria and some protozoans • Creates a highly reactive anionic radical • Effects microbes by: • Inhibiting lipid synthesis • Inhibits oxidative and peroxidative enzymes • These usually work to clean up free radicals, now they’re left in the cell causing damage to it and its DNA Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 37 Metronidazole (FLAGYL) Adverse Effects • Hypersensitivity • Common side-effects (12%) • • • • Headache Nausea Dry mouth Metallic taste • May cause urine to be red-brown coloured • Well-documented effect of slowing alcohol metabolism and can cause vomiting, flushing, and headache when alcohol is consumed concurrently Drug Interactions • None on the 884/93, but be cautious with ethanol consumption Slide Modified From: Dr. C. Beites, Laurentian University ©Dr. E. Cates 2023 38