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Antibiotics in Pregnancy

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14341. Telavancin

is possible. Use During Pregnancy and Breastfeeding Lipoglycopeptides have had some adverse effects on fetal development in animals; safety data in pregnant women are limited. Lipoglycopeptides should be used during pregnancy only if the potential benefit to the patient outweighs the potential risk to the fetus. There are no data regarding excretion in breast milk in humans, but lipoglycopeptides are known to be excreted in the breast milk of rats. Adverse Effects Common adverse effects (...) of lipoglycopeptides include Nausea and vomiting Taste disturbance Foamy urine Telavancin and oritavancin may falsely increase values on coagulation tests (PT/PTT) for a period of time. Therefore, blood for these tests should be drawn before these antibiotics are given. Telavancin interferes with urine protein assays. Significant adverse effects include A histamine-mediated pruritus and flushing of the face, neck, and shoulders, similar to the red-person syndrome that can occur with vancomycin Nephrotoxicity

2013 Merck Manual (19th Edition)

14342. Trimethoprim and Sulfamethoxazole

acid to dihydropteroate. This synergy results in maximal antibacterial activity, which is often bactericidal. Trimethoprim /sulfamethoxazole (TMP/SMX) is available as a fixed combination consisting of a 1:5 ratio (80 mg TMP plus 400 mg SMX or a double-strength tablet of 160 mg TMP plus 800 mg SMX). Pharmacokinetics Both drugs are well absorbed orally and are excreted in the urine. They have a serum half-life of about 11 h in plasma and penetrate well into tissues and body fluids, including CSF. TMP (...) include folate deficiency, liver dysfunction, and renal insufficiency. Use During Pregnancy and Breastfeeding Animal reproduction studies with TMP/SMX show some risk (eg, birth defects). Data related to pregnancy in humans is inadequate. However, use of TMP/SMX should be avoided during the 1st trimester (because neural tube defects are a risk) and near term. If used during pregnancy or in neonates, TMP/SMX increases blood levels of unconjugated bilirubin and increases risk of in the fetus or neonate

2013 Merck Manual (19th Edition)

14343. Nitrofurantoin

to it Renal insufficiency (creatinine clearance < 60 L/min) Age < 1 mo Pregnancy at term (38 to 42 wk gestation), during labor and delivery, or when the onset of labor is imminent. Use During Pregnancy and Breastfeeding Animal reproduction studies with nitrofurantoin have not shown risk to the fetus. No adequate and well-controlled studies have been done in pregnant women, but nitrofurantoin is generally considered to be safe during all 3 trimesters of pregnancy.. However, nitrofurantoin (...) -resistant strains, and Klebsiella and Enterobacter sp are less susceptible. Most strains of Proteus , Providencia , Morganella , Serratia , Acinetobacter , and Pseudomonas spp are resistant. There is no cross-resistance with other antibiotic classes. Nitrofurantoin is used only for Treatment or prophylaxis of uncomplicated lower UTI ( ) In women with recurrent UTIs, it may decrease the number of episodes. Contraindications Contraindications to nitrofurantoin use include Previous allergic reaction

2013 Merck Manual (19th Edition)

14344. Rifamycins

superior activity in vitro and reduced drug interaction potential. Rifapentine is used to treat pulmonary TB and latent TB. Contraindications Rifampin and rifabutin are contraindicated in patients who have had an allergic reaction to them. Use During Pregnancy and Breastfeeding Some animal reproduction studies with rifabutin showed adverse effects when drug levels were higher than those typically achieved in humans. No adequate and well-controlled studies have been done in pregnant or breastfeeding (...) , University of Washington School of Pharmacy Click here for Patient Education NOTE: This is the Professional Version. CONSUMERS: Topic Resources The rifamycins are bactericidal ; they inhibit bacterial DNA-dependent RNA polymerase, suppressing RNA synthesis (see table ). Table Rifamycins Rifabutin Rifampin Rifaximin Rifapentine Rifabutin , Rifampin , and Rifapentine Rifabutin , rifampin , and rifapentine have similar pharmacokinetics, antimicrobial spectra, and adverse effects. Pharmacokinetics Oral

2013 Merck Manual (19th Edition)

14345. Metronidazole

; lung abscess) Often used with other antimicrobials Drug of choice — CNS infections ( , ) — — Septicemia — Prophylaxis before intestinal surgery — (pseudomembranous colitis) Oral use preferable Peptic ulcers due to For treatment and prevention of relapses Used with other drugs Topical or oral use Contraindications Metronidazole is contraindicated in patients who have had an allergic reaction to it. Use During Pregnancy and Breastfeeding Reproduction studies with metronidazole in some animal species (...) showed increased risk of carcinogenic activity. No adequate and well-controlled studies have been done in pregnant women. Most human studies have not shown increased risk of cancer, birth defects, or other fetal adverse effects after use of metronidazole during pregnancy; however, in some studies, cleft lip (with or without cleft palate) was reported in neonates of women who took metronidazole during the 1st trimester. Some experts advise avoiding metronidazole during the 1st trimester, although

2013 Merck Manual (19th Edition)

14346. Linezolid and Tedizolid

), vasopressors (eg, epinephrine , norepinephrine ), or dopaminergic drugs (eg, dopamine , dobutamine ) Those with uncontrolled hypertension Those with thyrotoxicosis Those with a pheochromocytoma Use During Pregnancy and Breastfeeding Animal reproduction studies with linezolid show some risk, and no adequate, well-controlled studies have been done in pregnant women. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Whether linezolid is excreted (...) counts of < 1000 cell/mcL. Use During Pregnancy and Breastfeeding Animal reproduction studies with tedizolid show some risk, and no adequate and well-controlled studies have been done in pregnant women. Tedizolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Whether linezolid is excreted in breast milk or is safe to use during breastfeeding is unknown. Last full review/revision July 2018 by Brian J. Werth, PharmD NOTE

2013 Merck Manual (19th Edition)

14347. Clindamycin

be used with caution in those who have a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis. Use During Pregnancy and Breastfeeding Animal reproduction studies with clindamycin have not shown risk to the fetus. In clinical trials with pregnant women, clindamycin given during the 2nd and 3rd trimesters has not been associated with an increased frequency of birth defects. If medically indicated, clindamycin can be used during pregnancy. Clindamycin enters breast milk (...) , clindamycin resistance has emerged among these organisms in some regions. Because these infections often also involve aerobic gram-negative bacilli, additional antibiotics are also used. Clindamycin is part of combination therapy for the following: Infections caused by toxigenic streptococci (because clindamycin decreases the bacteria’s toxin production) Clindamycin can be used for infections (eg, skin and soft-tissue infections) in communities where community-associated methicillin-resistant

2013 Merck Manual (19th Edition)

14348. Fosfomycin

infections with multidrug-resistant organisms at other anatomic sites. Contraindications There are no significant contraindications to its use other than known hypersensitivity to fosfomycin or to any component of the formulation. Use During Pregnancy and Breastfeeding Fosfomycin crosses the placenta but is generally considered to be safe for treatment of cystitis in pregnant women. How much fosfomycin enters breast milk is unknown, and caution is advised if treatment with fosfomycin is necessary (...) of Washington School of Pharmacy Click here for Patient Education NOTE: This is the Professional Version. CONSUMERS: Fosfomycin is a novel class of with a chemical structure unrelated to other known antibiotics. It is a bactericidal drug that disrupts cell wall synthesis by inhibiting phosphoenolpyruvate synthetase and thus interferes with the production of peptidoglycan. In the US, it is available only as a powder formulation of fosfomycin tromethamine , which can be dissolved in liquid and taken orally

2013 Merck Manual (19th Edition)

14349. Chloramphenicol

susceptible to this antibiotic because other plague drugs penetrate these spaces poorly However, when chloramphenicol has been used to treat meningitis caused by relatively penicillin-resistant pneumococci, outcomes have been discouraging, probably because chloramphenicol has poor bactericidal activity against these strains. Contraindications Chloramphenicol is contraindicated if another drug can be used instead. Use During Pregnancy and Breastfeeding Use of chloramphenicol during pregnancy results (...) , active chloramphenicol does not accumulate when renal insufficiency is present. Indications Chloramphenicol has a wide spectrum of activity against Gram-positive and gram-negative cocci and bacilli (including ) , , , and Chlamydophila spp Because of bone marrow toxicity, the availability of alternative antibiotics, and the emergence of resistance, chloramphenicol is no longer a drug of choice for any infection, except for Serious infections due to a few multidrug-resistant bacteria that remain

2013 Merck Manual (19th Edition)

14350. Fluoroquinolones

, PharmD, University of Washington School of Pharmacy Click here for Patient Education NOTE: This is the Professional Version. CONSUMERS: Topic Resources Fluoroquinolones (see table ) exhibit by inhibiting the activity of DNA gyrase and topoisomerase, enzymes essential for bacterial DNA replication. Fluoroquinolones are divided into 2 groups, based on antimicrobial spectrum and pharmacology: Older group: Ciprofloxacin , norfloxacin , and ofloxacin Newer group: Delafloxacin, gemifloxacin , levofloxacin (...) to be contraindicated in children because they may cause cartilage lesions if growth plates are open. However, some experts, who challenge this view because evidence is weak, have recommended prescribing fluoroquinolones as a 2nd-line antibiotic and restricting use to a few specific situations, including P. aeruginosa infections in patients with cystic fibrosis, prophylaxis and treatment of bacterial infections in immunocompromised patients, life-threatening multiresistant bacterial infections in neonates

2013 Merck Manual (19th Edition)

14351. Penicillins

and are usually used with this class to treat P. aeruginosa infections. Contraindications Penicillins are contraindicated in patients who have had serious allergic reactions to them. Use During Pregnancy and Breastfeeding Penicillins are among the safest antibiotics during pregnancy. Animal reproduction studies with penicillin have not shown risk to the fetus. Data related to pregnancy in humans are limited . If medically indicated, penicillins can be used during pregnancy. Penicillin G is effective (...) -lactam antibiotics; this effect can be blocked by adding a beta-lactamase inhibitor. However, traditional beta-lactamase inhibitors (eg, clavulanate, sulbactam, tazobactam) do not reliably inhibit the following: AmpC beta-lactamases, commonly produced by Enterobacter , Serratia , Citrobacter , Providencia , and Morganella spp or by Pseudomonas aeruginosa Extended-spectrum beta-lactamases (ESBLs) produced by some Klebsiella pneumoniae , Escherichia coli , and other Enterobacteriaceae Carbapenemases

2013 Merck Manual (19th Edition)

14352. Leprosy

. Treatment is typically with dapsone plus other antimycobacterial drugs. Patients rapidly become noncontagious after starting therapy. M. leprae was the only known cause of leprosy until 2008, when a second species, M. lepromatosis was identified in Mexico. Although leprosy is not highly contagious, rarely causes death, and can be effectively treated with antibiotics, it continues to be associated with considerable social stigma. Misunderstanding about the disease probably exists because leprosy (...) was incurable before the advent of effective antibiotic therapy in the 1940s. People with the disease would become disfigured and often have significant disability, causing them to be feared and shunned by others. Because of this social stigma, the psychologic impact of leprosy is often significant. Epidemiology Globally, the number of leprosy cases is declining. During 2016, about 215,000 new cases were reported ( ). In 2015, about 80% of cases occurred in India, Brazil, and Indonesia. In 2015, 178 new

2013 Merck Manual (19th Edition)

14353. Other Mycobacterial Infections Resembling Tuberculosis

destruction of the skin and soft tissue; large ulcers may form on the legs or arms. Healing may result in a severe contracture, scarring, and deformity. For diagnosis, PCR should be used. The WHO recommends 8 wk of once/day combination therapy with rifampin 10 mg/kg po plus either streptomycin 15 mg/kg IM, clarithromycin 7.5 mg/kg po (preferred during pregnancy), or moxifloxacin 400 mg po. Wounds and foreign body infections Nontuberculous mycobacteria form biofilms; they can survive in water systems (...) is recommended. Duration of therapy averages 24 mo and may be longer if the infected foreign body remains in the body. Amikacin is usually included for the first 3 to 6 mo of therapy. Infections caused by M. abscessus and M. chelonae are usually resistant to most antibiotics, have proved extremely difficult or impossible to cure, and should be referred to an experienced specialist. Disseminated disease MAC causes disseminated disease commonly in patients with advanced AIDS and occasionally in those

2013 Merck Manual (19th Edition)

14354. Tuberculosis (TB)

by language and cultural barriers. For similar reasons, EMB is usually avoided in young children who cannot read eye charts but can be used if needed because of drug resistance or drug intolerance. Another drug is substituted for EMB if optic neuritis occurs. Ethambutol can be used safely during pregnancy. Resistance to EMB is less common than that to the other first-line drugs. Second-line drugs Other antibiotics are active against TB and are used primarily when patients have drug-resistant TB (DR-TB (...) diagnostic tests. Treatment is with multiple antimicrobial drugs given for at least 6 mo. (See also .) Mycobacteria are small, slow-growing, aerobic bacilli. They are distinguished by a complex, lipid-rich cell envelope responsible for their characterization as acid-fast (ie, resistant to decolorization by acid after staining with carbolfuchsin) and their relative resistance to Gram stain. The most common mycobacterial infection is tuberculosis; others include and various , such as those caused

2013 Merck Manual (19th Edition)

14355. Human Immunodeficiency Virus (HIV) Infection

they are pregnant, in labor, and breastfeeding. Cesarean delivery and treatment of the infant for several weeks after birth also reduce the risk. Because many HIV-positive pregnant women are treated or take prophylactic drugs, the incidence of AIDS in children is decreasing in many countries (see ). Transfusion- and transplant-related transmission Screening of blood donors with tests for both antibody to HIV and HIV RNA has minimized risk of transmission via transfusion. Current risk of transmitting HIV via (...) of stools or biopsy, but determination of cause possibly difficult For all, supportive treatment for symptoms, treatment of cause, and prompt initiation of antiretroviral drugs, as for the following: Antibiotics for Salmonella , MAC, and C. difficile Prompt use of antiretroviral drugs for Cryptosporidium , Cyclospora , and microsporidia TMP/SMX for Cyclospora , Cystoisospora , and microsporidia Antiviral drugs for CMV Diarrhea, weight loss, abdominal cramping Cholecystitis or cholangitis CMV

2013 Merck Manual (19th Edition)

14356. Extrapulmonary Tuberculosis

molecular-based diagnostic tests. Treatment is with multiple antimicrobial drugs given for at least 6 mo. Miliary TB Also known as generalized hematogenous TB, miliary TB occurs when a tuberculous lesion erodes into a blood vessel, disseminating millions of tubercle bacilli into the bloodstream and throughout the body. Uncontrolled massive dissemination can occur during primary infection or after reactivation of a latent focus. The lungs and bone marrow are most often affected, but any site may (...) pregnancy due to tubal scarring. TB meningitis Meningitis often occurs in the absence of infection at other extrapulmonary sites. In the US, it is most common among the elderly and immunocompromised, but in areas where TB is common among children, TB meningitis usually occurs between birth and 5 yr. At any age, meningitis is the most serious form of TB and has high morbidity and mortality. It is the one form of TB believed to be prevented in childhood by vaccination with . Symptoms are low-grade fever

2013 Merck Manual (19th Edition)

14357. Aminoglycosides

outweigh risk. If an aminoglycoside is used during pregnancy or if the patient becomes pregnant while taking an aminoglycoside, she should be apprised of the potential hazard to the fetus. Aminoglycosides enter breast milk but are not well absorbed orally. Thus, they are considered compatible with use during breastfeeding. Adverse Effects All aminoglycosides cause Renal toxicity (often reversible) Vestibular and auditory toxicity (often irreversible) Prolongation of effects of neuromuscular blockers (...) , PharmD, University of Washington School of Pharmacy Click here for Patient Education NOTE: This is the Professional Version. CONSUMERS: Topic Resources Aminoglycosides (see table ) have concentration-dependent bactericidal activity. These bind to the 30S ribosome, thereby inhibiting bacterial protein synthesis. is a bacteriostatic antibiotic chemically related to the aminoglycosides. Table Aminoglycosides Amikacin Gentamicin Kanamycin * Neomycin * Streptomycin Tobramycin *Should be used topically

2013 Merck Manual (19th Edition)

14358. Tetanus

by debriding the wound and giving an Neutralize unbound toxin outside the CNS with human tetanus immune globulin and tetanus toxoid, taking care to inject into different body sites and thus avoid neutralizing the antitoxin Minimize the effect of toxin already in the CNS Wound care Because dirt and dead tissue promote C. tetani growth, prompt, thorough debridement, especially of deep puncture wounds, is essential. Antibiotics are not substitutes for adequate debridement and immunization. Antitoxin (...) and reduce norepinephrine release from nerve endings Dexmedetomidine (a potent alpha-2 adrenergic agonist) Adenosine , which reduces presynaptic norepinephrine release and antagonizes the inotropic effect of catecholamines Corticosteroids are of unproven benefit; their use is not recommended. Antibiotics The role of antibiotic therapy is minor compared with wound debridement and general support. Typical antibiotics include penicillin G 6 million units IV q 6 h, doxycycline 100 mg po bid

2013 Merck Manual (19th Edition)

14359. Overview of Transplantation

results from prior blood transfusions, transplantations, or pregnancies and can be detected with serologic tests or, more commonly, with a lymphocytotoxic test using the recipient’s serum and donor’s lymphocytes in the presence of complement. A positive cross-match indicates that the recipient’s serum contains antibodies directed against ABO or class I HLA antigens in the donor; it is an absolute contraindication to transplantation, except possibly in infants (up to age 14 mo) who have not yet (...) of immunosuppressants (5 to 10%), and remain at high risk of opportunistic infections indefinitely. Risk of infection varies depending on the graft received and is lowest for recipients of kidney allografts and highest for recipients of liver and lung transplants. After transplantation, most patients are given antimicrobials to reduce risk of infection. Choice of drug depends on individual risk and type of transplantation; regimens include trimethoprim /sulfamethoxazole 80/400 mg po once/day for 4 to 12 mo

2013 Merck Manual (19th Edition)

14360. X-linked Agammaglobulinemia

can increase the frequency of both teratogen education and urine pregnancy... Video Overview of Antibody-Mediated Immunity Antibody-mediated immunity involves the activation of B cells and secretion of antibodies when in contact with a pathogen. When exposed to the chemicals released by activated helper... SOCIAL MEDIA Add to Any Platform Loading X-linked agammaglobulinemia is characterized by low levels or absence of immunoglobulins and absence of B cells, leading to recurrent infections (...) , mutational analysis of chorionic villus, amniocentesis, or percutaneous umbilical cord blood samples can provide prenatal diagnosis. Treatment Immune globulin replacement therapy Treatment of X-linked agammaglobulinemia is . Prompt use of adequate antibiotics for each infection is crucial; bronchiectasis may require frequent rotation of antibiotics. Live-virus vaccines are contraindicated. Last full review/revision June 2018 by James Fernandez, MD, PhD NOTE: This is the Professional Version. CONSUMERS: ©

2013 Merck Manual (19th Edition)

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