中国科技论文统计源期刊 中文核心期刊
美国《化学文摘》《国际药学文摘》
《乌利希期刊指南》
WHO《西太平洋地区医学索引》来源期刊
日本科学技术振兴机构数据库（JST）
第七届湖北十大名刊提名奖
美国《化学文摘》《国际药学文摘》
《乌利希期刊指南》
WHO《西太平洋地区医学索引》来源期刊
日本科学技术振兴机构数据库（JST）
第七届湖北十大名刊提名奖
, 陈诚
, CHEN Cheng
乳腺炎常见于哺乳期患者,发病时常伴随局部或全身症状,严重影响患者的生活质量。世界卫生组织推荐婴儿出生6个月内应该纯母乳喂养,2岁以下甚至超过2岁者可以在添加辅食的基础上进行母乳喂养。拒绝用药、不合理用药或对药物安全性担忧常导致母乳喂养过早停止,为婴儿带来潜在的安全隐患。该文综述了哺乳期乳腺炎患者的用药原则、药物的安全性评价及哺乳期乳腺炎的药物选择,为哺乳期乳腺炎的治疗和母乳喂养提供一定的参考。
Mastitis is common in patients during breast-feeding, who is frequently accompanied by local or systemic symptoms affecting the daily life of patients severely.According to the recommendation of World Health Organization(WHO), babies should be exclusively breastfed within six months, toddlers under or even over 2 years old can be breastfeed on the basis of complementary foods.Refusal of medication, unreasonable use of drugs, or concerns about drug safety often lead to the premature cessation of breastfeeding, posing potential risks for infants.This paper reviewed the principle of drug use, evaluation of drug safety and drug selection of lactation mastitis, which provided some references to the treatment and breastfeeding of lactation mastitis.
哺乳期妇女乳腺炎发生率3%~33%[6,7],以初产妇较为多见。哺乳期乳腺炎可以发生在哺乳期任一阶段,最常见于产后前3个月,发病高峰多出现在新生儿娩出后3~4周。临床表现多见发热,单侧乳房皮肤红肿、胀痛等。其具体发病机制尚不清楚,可能由乳汁淤积、乳头皲裂、细菌经乳头裂口感染所致,但现在也认为可能与自身的炎症性反应信号免疫通路有关。乳腺炎早期症状轻者可以选择在哺乳前热敷,排空乳汁后进行局部冷敷[8],帮助局部血运循环和清除坏死物质,尽管目前认为,哺乳期乳腺炎的发病机制已经由感染性疾病向炎症性疾病转换,但是抗菌药物仍是主要的治疗药物。尤其当患者伴有明显感染症状或炎症指标异常时,需要及时使用抗菌药物。早期的排空乳汁可以明显缓解病情,但是病程超过1 d者常合并细菌感染,如果未及时治疗,可导致病情进展,形成局部的脓肿,只能通过外科手术进行切开引流,给患者造成不必要的痛苦,因此发现细菌感染时尽早使用抗菌药物是非常必要的。
哺乳期乳腺炎患者用药原则包括:①依据患者病情决定是否用药;②早期轻症患者可以选择物理治疗或局部外用药物;③细菌感染者宜尽早全身使用抗菌药物,避免乳腺脓肿的形成;④选择安全性高、半衰期短、乳汁中浓度低的普通剂型,尽量避免使用缓控释制剂;⑤为了避免婴儿接触到母乳中的药物,建议在哺乳后或睡前服药[9]。对于需要暂停哺乳的药物,需要等待5~6个半衰期的药物消除时间,同时即使安全的药物也需要尽量避免在母体血药浓度高峰期哺乳;⑥乳母使用安全性不明的药物后,需要暂停哺乳,同时换用更安全的替代药物;⑦胃肠功能较差的早产儿、新生儿和患病儿童,用药风险通常更高,>6个月的婴儿则很少出现不良反应。
哺乳期用药安全性要求比妊娠期更高,虽然大多数的药物都会不同程度地分泌入乳汁,但转运到乳汁中的量非常低[10]。Hale博士按照药物在哺乳期的安全性将其分为L1~L5五个等级,L1级药物使用最安全,L5级则禁止在哺乳期使用。评估药物在哺乳期使用的安全性主要依据为Hale博士哺乳期危险的等级、e-lactancia分级、药物说明书等,同时也需要参考药物与哺乳数据库(LactMed)、世界卫生组织(WHO)和美国儿科学会(American Academy of Pediatrics,AAP)的推荐。药物是否进入乳汁常常取决于药物本身的性质和母体的血药浓度、乳腺血流量等。分子质量小、蛋白结合率低、脂溶性低的药物更容易进入乳汁中,常用于评价药物进入乳汁中剂量的指标包括相对婴儿剂量和乳汁/血浆比值。乳汁中药物的达峰时间一般比血浆晚30~120 min,且乳汁中药物消除较慢,随血中药物消除而逐渐消除,多数药物在5~6个半衰期后几乎完全从体内消除。但是当母亲使用了可能影响婴儿生长发育的药物时,则应该延长暂停哺乳的时间。药物进入乳汁后需要经过婴儿消化道的吸收,才能进入婴儿体内。许多药物虽然在乳汁中有一定浓度,但是由于其在胃肠道不吸收或者不稳定,容易被破坏,药物不容易通过乳汁进入婴儿体内,同时首关效应也会影响药物进入婴儿的剂量。需要注意的是乳腺炎可能破坏乳腺相邻上皮细胞间的紧密连接,导致进入乳汁中的药量增加[11]。
目前认为,哺乳期乳腺炎患者乳汁中可以培养出致病菌,但这不会引起婴儿的感染风险增加,母乳喂养的益处大于风险。急性乳腺炎早期,继续母乳喂养有助于排除淤积的乳汁,减轻局部症状,有利于疾病治疗。出现乳腺脓肿或破溃后,患侧不再哺乳,并且需要定期排空患侧乳汁,保持乳腺导管的通畅,此时可用健侧乳房哺乳。如果感染进一步加重,出现乳腺脓肿并切开引流或发生乳瘘时需要使用回奶药物,完全停止哺乳。
哺乳期乳腺炎常见的用药包括对症治疗、抗菌药物和一些中药的内服外用等。出于安全性考虑,哺乳期避免使用非必要的用药,对于早期由乳汁淤积引起的非感染性炎症,可以采用排空乳汁、局部热敷与按摩等物理治疗。当病情进展需要用药时,可以选择较安全的给药方式,如在没有皮肤破溃或乳头皲裂时,地塞米松或硫酸镁局部湿敷,可以促进局部炎症的恢复。哺乳期感染性乳腺炎常见感染细菌为革兰阳性球菌,以金黄色葡萄球菌最为常见[12]。金黄色葡萄球菌是一种化脓性细菌,若不及时治疗可能引起局部的脓肿形成,甚至造成不可逆的损伤。针对炎症指标升高的感染性乳腺炎,需要及时使用抗菌药物。
乳腺炎早期的局部炎症症状可以通过外用硫酸镁或地塞米松缓解。硫酸镁的高渗透性及扩张外周血管作用,能促进炎症的恢复,消除局部肿胀。地塞米松抗炎作用强大,对炎症的各个阶段均有效。乳腺炎早期,地塞米松通过增加血管紧张性、降低毛细血管通透性,减轻炎症部位的渗出和水肿,同时抑制白细胞浸润及吞噬反应,减少炎症因子释放,改善炎症症状。乳腺炎后期,该药能抑制毛细血管和成纤维细胞的增生,减少炎症的粘连及瘢痕。地塞米松用于局部外敷能减轻局部组织的水肿和炎症症状,有利于乳汁的排出,治疗效果优于硫酸镁外敷。据报道,1例哺乳期母亲一直使用局部激素治疗乳头疼痛,其2个月大的乳儿出现了QT间期延长、库欣样外观、严重高血压、生长迟缓和电解质紊乱等不良反应,同时婴儿下丘脑-垂体-肾上腺轴(hypothalamic-pituitary-adrenal axis,HPA )受到了显著的抑制[13]。由于母乳喂养时婴儿可直接接触乳房上涂抹的激素,因此为了避免婴儿直接接触导致不良反应,乳房尽量避免外用强效糖皮质激素,但可以选择效力较低的糖皮质激素(如氢化可的松和曲安奈德)[14,15]。为了乳儿的安全,仍需要避免直接接触,哺乳前将残留药物清洗干净。
哺乳期乳腺炎伴发热、疼痛者常用的解热镇痛药包括布洛芬和对乙酰氨基酚,二者均为L1级哺乳期用药。对乙酰氨基酚的半衰期为2 h,药物从乳汁中的分泌量远远低于临床治疗水平,成人单次使用1000 mg,乳汁中的平均含量只有6.1 mg·L-1,远低于儿科的临床治疗剂量,认为其在哺乳期使用较安全;布洛芬在哺乳期的安全性数据较多,退热作用比对乙酰氨基酚起效快,且后者抗炎作用弱,其半衰期短,99%的蛋白结合率使其分泌入乳汁中的量非常少,美国LactMed数据库中推荐将布洛芬作为哺乳期首选的非甾体抗炎药。哺乳期母亲每次服用布洛芬400 mg,每天4次,母乳中布洛芬不能测出[16]。国内说明书中布洛芬禁用于哺乳期,用药之前应该获得患者知情同意。以上两药均没有哺乳期母亲用药后,乳儿发生不良反应的报道,用药期间均可以继续哺乳,但是建议避开乳汁浓度高峰期,并在哺乳后注意监测婴儿呕吐、腹泻等不良反应。
4.3.1 无耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)危险因素的轻症感染 哺乳期感染性乳腺炎的细菌药敏试验提示培养出的大多数细菌对青霉素和大环内酯类抗菌药物耐药率较高,对于轻症感染的患者可予以双氯西林或头孢氨苄口服,就哺乳期安全性而言,也可以选择不分泌入乳汁中的头孢妥仑匹酯。克林霉素一般用于β内酰胺类过敏者[17]。双氯西林哺乳期分级为L1级,在乳汁中浓度很低,口服双氯西林250 mg后第2~4小时,能检测出低浓度的双氯西林,服药后1 h内和服药6 h后乳汁中药物浓度不能测出[18];头孢氨苄为第1代头孢菌素类,半衰期为0.5~1.2 h,血中达峰时间为1 h,乳汁中达峰时间较晚,为4~5 h。文献报道1例母亲在服用该药后哺乳后,乳儿发生腹泻,但是尚未证明相关性[19]。该药哺乳期分级为L1级,乳汁中药物浓度极低,服药时可以继续哺乳。头孢妥仑匹酯口服后吸收良好,能广泛分布于包括乳腺组织在内的各个组织器官中,但不分泌入乳汁,因此服用该药可以不用担心药物对哺乳的影响,是最安全的哺乳期抗菌药物。乳儿出现抗菌药物相关不良反应的时候可以使用该药。克林霉素为哺乳期L2级药物,具有高蛋白结合率,其半衰期为2.4~3 h。2例哺乳期母亲口服克林霉素300 mg,每日4次,用药后1.5~7 h,乳汁中平均血药浓度为1~1.7 mg·
4.3.2 有MRSA危险因素的轻症感染 MRSA感染在临床上越来越常见[21],有MRSA危险因素的轻症感染患者,可以选择复方磺胺甲··唑或克林霉素,复方磺胺甲··唑是一种磺胺类的复方制剂,哺乳期分级为L3级,半衰期约10 h,少量药物可通过乳汁分泌。对于月龄>1个月的足月儿,每次1片,每天2次,纯母乳喂养的婴儿从乳汁中吸收的药量远低于治疗剂量。由于其可以竞争性血浆白蛋白,置换出胆红素,可能引起胆红素血症,甚至导致新生儿或早产儿核黄疸,早产儿、高胆红素血症新生儿、葡萄糖-6-磷酸脱氢酶缺陷的婴儿和出生不足1个月的婴儿应该慎用。为避免药物对婴儿的不良影响,服用该药后最好等待5~6个半衰期后再行哺乳。
4.3.3 可能由MRSA导致的重症感染 重症感染是指在抗菌药物治疗期间发生血流动力学不稳定或进展性红斑,可以经验性地使用万古霉素静脉输注。后续治疗方案应根据细菌培养、药敏试验结果以及临床症状进行调整。万古霉素在哺乳期分级为L1级,适用于哺乳期母亲的感染性疾病,半衰期为4.3~5.2 h,其相对分子质量为1449,在胃肠道几乎不吸收,口服吸收进入乳汁的量极少。静脉用药能分泌入乳汁,乳汁中药物很少吸收入乳儿体内,因此认为该药在哺乳期使用时可以继续哺乳。但是因为其在胃肠道可能会引起乳儿胃肠菌群紊乱,因此建议患者避开血药浓度高峰哺乳,尽量延长服药到哺乳的时间。
哺乳期乳腺炎严重影响哺乳期患者的生活质量,部分患者担心哺乳或用药对乳儿的影响擅自停止哺乳,为乳儿带来了潜在的风险。目前认为,虽然哺乳期乳腺炎患者乳汁中可以培养出致病菌,但这不会引起婴儿的感染风险增加,母乳喂养的益处大于风险。乳腺炎早期,应该根据患者病情选择相应的治疗手段,保证母体疾病得到及时的治疗,同时建议患者在安全用药的前提下继续母乳喂养。为了减少婴儿接触到乳汁中的药物,建议选择哺乳期安全性较高的药物、延长用药与哺乳的间隔时间,在使用可能有风险的药物时等待5~6个半衰期后再行哺乳。
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| [2] |
Mebendazole is an effective drug widely used in the treatment of parasitic infections. Although theoretically considered as safe during lactation, no studies have evaluated its potential adverse effects in infants of breastfeeding mothers.
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| [3] |
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| [4] |
Safety of maternal drug therapy during breastfeeding may be assessed from estimated levels of drug exposure of the infant through milk. Pharmacokinetic (PK) principles predict that the lower the clearance is, the higher the infant dose via milk will be. Drugs with low clearance (<1 mL/[kg·min]) are likely to cause an infant exposure level greater than 10% of the weight-adjusted maternal dose even if the milk-to-plasma concentration ratio is 1. Most drugs cause relatively low-level exposure below 10% of the weight-adjusted maternal dose, but opioids require caution because of their potential for severe adverse effects. Furthermore, substantial individual variations of drug clearance exist in both mother and infant, potentially causing drug accumulation over time in some infants even if an estimated dose of the drug through milk is small. Such PK differences among individuals are known not only for codeine and tramadol through pharmacogenetic variants of CYP2D6 but also for non-CYP2D6 substrate opioids including oxycodone, indicating difficulties of eliminating PK uncertainty by simply replacing an opioid with another. Overall, opioid use for pain management during labor and delivery and subsequent short-term use for 2-3 days are compatible with breastfeeding. In contrast, newly initiated and prolonged maternal opioid therapy must follow a close monitoring program of the opioid-naive infants. Until more safety data become available, treatment duration of newly initiated opioids in the postpartum period should be limited to 2-3 days in unsupervised outpatient settings. Opioid addiction treatment with methadone and buprenorphine during pregnancy may continue into breastfeeding, but infant conditions must be monitored.
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Despite an increased uptake of option B+ treatment among HIV- positive pregnant and breastfeeding women, retaining these women in care is still a major challenge. Previous studies have identified factors associated with loss to follow-up (LTFU) in HIV care, however, the perspectives from HIV-positive pregnant and breastfeeding women regarding their LTFU in option B+ needs further exploration. We explored reasons for LTFU and motivation to resume treatment among HIV-positive women initiated in option B+ in an Urban setting.
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Evidence continues to mount regarding the value of breastfeeding for both women and their infants. The American College of Obstetricians and Gynecologists strongly supports breastfeeding and calls on its Fellows, other health care professionals caring for women and their infants, hospitals, and employers to support women in choosing to breastfeed their infants. Obstetrician-gynecologists and other health care professionals caring for pregnant women should provide accurate information about breastfeeding to expectant mothers and be prepared to support them should any problems arise while breastfeeding.
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The aim of this prospective study was to compare serum C-reactive protein (CRP) and leukocytes, hemoglobin, clinical signs, treatment, and outcome among 41 episodes of lactation mastitis grouped by the outcome of bacterial cultivation of breast milk. Group A included 25 cases with positive cultures only for bacteria normally present on skin. Group B included 16 cases in which cultures indicated the presence of potentially pathogenic bacteria. Serious complications were observed among women in group B, including protracted illness and weaning. No complications were observed in group A. Staphylococcus aureus was the most frequently isolated bacteria in group B. Mean serum leukocytes were significantly higher in group B than in group A. Although CRP levels in both groups were elevated, no significant difference was found between groups. Rest and frequent emptying of the breast were curative in group A. Further interventions were necessary for mothers in group B.
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A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.
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| [9] |
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This article reviews the necessary skills required for clinicians to make informed decisions about the use of medications in breastfeeding women. Even without specific data on certain medications, this review of kinetic principles, mechanisms of medication entry into breast milk, and important infant factors can aid in clinical decision making. In addition, the article reviews common medical conditions (eg, depression, hypertension, infections) in breastfeeding women and their appropriate treatment.
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Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species.
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Mastitis is a common infectious disease during lactation, and the main etiological agents are staphylococci, streptococci, and/or corynebacteria. The efficacy of oral administration of Lactobacillus fermentum CECT5716 or Lactobacillus salivarius CECT5713, two lactobacilli strains isolated from breast milk, to treat lactational mastitis was evaluated and was compared with the efficacy of antibiotic therapy.
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A 2-month-old breast-fed baby is described, who, admitted for a prolongation of the QT interval on ECG, was found to be severely hypokalemic, alkalotic and hypertensive (blood pressure 200/100 mm Hg). Marked generalized hypotonia was present, and length was less than 3% for age. The results of endocrinological evaluation showed profound suppression of the pituitary-adrenal function and of the renin-aldosterone mechanism. CT scan, cavography and pyelography were normal. A pharmacological cause for the symptoms was sought and found: the mother had been using for the care of bruised nipples a cream containing 1% 9-alpha-fluoroprednisolone-21-acetate. Blood pressure remained elevated for 6 months, but became normal after one year, and growth has resumed normally. The possible differential diagnoses are considered, and the risks presented by topical steroids are emphasized.
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| [14] |
Dermatoses of the breast during lactation can be difficult to diagnose because of their overlapping clinical appearances. It is important to properly diagnose and treat nipple dermatitis since it can be a significant source of pain when nursing. Poorly controlled nipple pain in nursing mothers is one of the primary reasons for breastfeeding to be discontinued earlier than is recommended. Therefore, it is relevant for practicing dermatologists to be aware of certain facts in a patient's history, specific physical exam findings, and the most appropriate laboratory tests used to diagnose these conditions. In addition, the therapeutic approach should be effective and safe for the mother and infant. This review article provides dermatologists with a detailed discussion on the clinical features and management of various breast dermatoses seen in lactation, including atopic dermatitis, irritant contact dermatitis, allergic contact dermatitis, psoriasis, bacterial infections, yeast infections and herpes simplex virus infections.
DOI:10.1111/dth.12071
URL
[本文引用:1]
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| [15] |
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| [16] |
Concentrations of ibuprofen in breast milk and serum were compared in 12 patients who had ingested one 400 mg tablet of ibuprofen every 6 hours over a 24-hour period for relief of post-cesarean section pain. Samples of breast milk and blood were obtained simultaneously over a 34-hour period beginning just prior to the first dose of ibuprofen. Gas-liquid chromatography assay methodology capable of detecting 1 microgram/ml was used to determine concentrations of ibuprofen in serum and breast milk. Ibuprofen was present in the serum with a half-life of approximately 1.5 hours. No measurable amounts of ibuprofen were found in the samples of breast milk. The conclusion drawn is that, in lactating women who take up to 400 mg of ibuprofen every 6 hours, less than 1 mg of ibuprofen per day is excreted in breast milk.
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| [17] |
Mastitis can be caused by ineffective positioning of the baby at the breast or restricted feeding. Infective mastitis is commonly caused by Staphylococcus aureus . The prevalence of mastitis in breastfeeding women may reach 33%. Effective milk removal, pain medication and antibiotic therapy have been the mainstays of treatment.
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| [18] |
Thirty antibiotics, including penicillins, cephems, chloramphenicol, tetracyclines, macrolides, and aminoglycosides, were given p.o., i.m. or i.v. once to 70 puerperal women to compare milk drug levels with serum levels over a 6-h period. Antibiotic transfer into the milk was small. No drugs except for a few (chloramphenicol, tetracyclines, macrolides) reached the level of 1 mcg/ml or greater. Penicillins and cephams detected in trace amounts in the milk are likely to have little effect on infants.
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| [19] |
Migraine affects up to 25% of women of reproductive age. In the majority of these women, migraine improves progressively during pregnancy, but symptoms generally recur shortly after delivery. As suboptimally treated migraine in pregnancy could have negative consequences for both mother and fetus, the primary aim of clinicians should be to provide optimal treatment according to stage of pregnancy, while minimising possible risks related to drug therapy. Nonpharmacological approaches are always first-line treatment, and should also be used to complement any required drug treatment. Paracetamol is the preferred drug for acute treatment throughout pregnancy. If paracetamol is not sufficiently effective, sporadic use of sumatriptan can be considered. NSAIDs such as ibuprofen can also be used under certain circumstances, though their intake in the first and third trimesters is associated with specific risks and contraindications. Preventive treatment should only be considered in the most severe cases. In women contemplating pregnancy, counselling is essential to promote a safe and healthy pregnancy and postpartum period for the mother and child, and should involve a dialogue addressing maternal concerns and expectations about drug treatment. This Review summarizes current evidence of the safety of the most common antimigraine medications during pregnancy and breastfeeding, and provides treatment recommendations for use in clinical practice.
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| [20] |
To report a case of the transfer of probenecid and cephalexin into human milk.
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| [21] |
Post-partum mastitis is a common infection in breastfeeding women, with an incidence of 9.5-16% in recent literature. Over the past decade, community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a significant pathogen in soft-tissue infections presenting to the emergency department. The incidence of mastitis caused by MRSA is unknown at this time, but likely increasing.
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| [22] |
The need for medication during lactation can contribute to the early cessation of breastfeeding.
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| [23] |
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