By G. Jaroll. University of Guam.

For instance purchase rocaltrol 0.25 mcg amex, glucagon can be used in the setting of β- blocker overdose; sodium bicarbonate and hemodialysis can be used for acidosis; calcium discount rocaltrol generic, insulin generic rocaltrol 0.25 mcg overnight delivery, and hemodialysis can be used in the setting of hyperkalemia (Table 189 best purchase for rocaltrol. Pacemaker Therapy Pacemakers are used to improve circulatory hemodynamics by improving cardiac output by controlling the heart rate and/or rhythm. Transcutaneous cardiac pacing is usually used in an emergent setting for patients not responsive to intravenous medications. However, owing to its instability and painful pacing, this modality should only be used as a temporizing measure for a short period of time. The pacing system is consisted of a pulse generator attached to high- impedance external patch electrode pads that are applied to the anteroposterior or anterolateral positions of the patient’s bare chest. The need for continued pacing can be evaluated by gradually decreasing pacing output, resulting in returning of stable rhythm. Transvenous endocardial pacing is predominantly used for patients with unstable bradyarrhythmias that will last for a period of time while waiting for permanent pacemaker implantation or resolving of underlying etiology. In transvenous pacing, the heart is directly paced using catheters placed in the apex of the right ventricle. Central venous access is achieved using an introducer sheath through the jugular, subclavian, femoral, or brachial veins [89]. A chest X-ray is then used to confirm placement of the catheter, and the pacing and sensing thresholds are tested. Yoshida T, Fujii T, Uchino S, et al: Epidemiology, prevention, and treatment of new-onset atrial fibrillation in critically ill: a systematic review. Tchou P, Young P, Mahmud R, et al: Useful clinical criteria for the diagnosis of ventricular tachycardia. Bou-Abboud E, Nattel S: Relative role of alkalosis and sodium ions in reversal of class I antiarrhythmic drug-induced sodium channel blockade by sodium bicarbonate. Eidher U, Freihoff F, Kaltenbrunner W, et al: Efficacy and safety of ibutilide for the conversion of monomorphic atrial tachycardia. Gonzalez-Torrecilla E, Almendral J, Arenal A, et al: Combined evaluation of bedside clinical variables and the electrocardiogram for the differential diagnosis of paroxysmal atrioventricular reciprocating tachycardias in patients without pre-excitation. Gupta A, Naik A, Vora A, et al: Comparison of efficacy of intravenous diltiazem and esmolol in terminating supraventricular tachycardia. D’Este D, Zoppo F, Bertaglia E, et al: Long-term outcome of patients with atrioventricular node reentrant tachycardia. Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Kodama S, Saito K, Tanaka S, et al: Alcohol consumption and risk of atrial fibrillation: a meta-analysis. Koniari I, Apostolakis E, Rogkakou C, et al: Pharmacologic prophylaxis for atrial fibrillation following cardiac surgery: a systematic review. Nattel S, Burstein B, Dobrev D: Atrial remodeling and atrial fibrillation: mechanisms and implications. Delle Karth G, Geppert A, Neunteufl T, et al: Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias. Kiss O, Sydo N, Vargha P, et al: Prevalence of physiological and pathological electrocardiographic findings in Hungarian athletes. Stockburger M, Trautmann F, Nitardy A, et al: Pacemaker-based analysis of atrioventricular conduction and atrial tachyarrhythmias in patients with primary sinus node dysfunction. Kornberger A, Schmid E, Kalender G, et al: Bridge to recovery or permanent system implantation: an eight-year single-center experience in transvenous semipermanent pacing. When the mean arterial blood pressure falls below approximately 60 mmHg, end-organ perfusion becomes compromised and is manifested clinically as cool skin, decreased urine output, and altered mental status. Cornerstones of management include volume resuscitation and therapy directed toward the underlying cause of hypotension (e. When these measures fail to restore blood pressure and vital organ perfusion or while awaiting their availability, administration of intravenous vasoactive agents may be necessary. This chapter reviews the general management of the hypotensive patient with an emphasis on coronary care and the pharmacologic properties of commonly used vasopressor and positive inotropic agents. An overview of shock (see Chapter 37); volume resuscitation (see Chapter 37); sepsis (see Chapter 39); and the use of intra-aortic balloon counterpulsation and mechanical circulatory support devices (see Chapter 196) is given elsewhere. This practice is especially important when automated devices are used to make these measurements in the setting of tachyarrhythmias or respiratory distress. For patients with peripheral arterial disease, upper extremity blood pressure should also be compared to measurements in the legs in the supine position. In rare circumstances, true central aortic pressure may differ significantly from peripherally obtained blood pressures and can only be confirmed by invasive measurement during diagnostic catheterization. This situation should be suspected when clinical features of hypoperfusion do not accompany low blood pressure. Hypotension is generally defined as a mean arterial pressure of less than 60 mmHg and/or a systolic blood pressure less than 100 mmHg. However, higher values may be consistent with clinically relevant hypotension if there are concomitant clinical signs of hypoperfusion such as mental status changes, oliguria, pallor, and cool extremities. If clinically relevant hypotension cannot be rapidly corrected, invasive monitoring with an arterial line should be considered, especially when vasoactive medications are employed. Central venous catheterization should also be considered to monitor intravascular volume, because volume status is often dynamic in the hypotensive patient and multiple mechanisms of hypotension may be simultaneously present. Indwelling urinary catheterization should also be employed to assess hourly urine output as an index of end-organ perfusion. Assessing volume status is critical; if not discernible from the bedside evaluation (jugular venous pressure, skin turgor, urine output, and orthostasis), echocardiography or invasive measurement of the central venous pressure should be obtained. If there are clinical reasons to suggest a dissociation of right and left ventricular hemodynamics (i. Warm well-perfused skin and extremities despite hypotension may suggest low systemic vascular resistance and a vasodilatory state, whereas cool clammy skin and extremities suggest vasoconstriction as a compensatory response to a low output syndrome. If a putative mechanism of hypotension cannot be ascertained from bedside assessment, pulmonary artery catheterization can be used to characterize the hemodynamic profile. This strategy is especially useful when more than one mechanism is present (for example, a large myocardial infarction complicated by pneumonia, leading to cardiogenic shock along with vasodilatory shock). Initial management strategies are directed at the primary cause of hypotension and addressed later in this chapter. In general, therapy is guided by the primary pathophysiologic mechanism underlying the hypotension (e. The pace and aggressiveness of therapeutic intervention are guided by the presence or absence of clinical signs of hypoperfusion. For example, holding vasodilators may be sufficient for the hypotensive patient without changes in mental status or urine output. In contrast, the acutely hypotensive patient with clinical shock needs rapid resuscitation with intravascular volume expansion and usually vasoactive therapy. To better understand the similarities and differences among these agents, a basic knowledge of adrenergic receptor distribution and function is helpful [1]. The adrenergic receptors that are most relevant to the management of hypotension are the α1, β1, and β2 receptors. The presence of α1 receptors has also been demonstrated in the myocardium, where stimulation appears to result in a positive inotropic effect with little change in heart rate. Stimulation of β2-adrenergic receptors causes relaxation of smooth muscle cells in bronchial, gastrointestinal, and uterine muscle, as well as vasodilation of skeletal muscle. Thus, at low doses of epinephrine, the vasodilatory effect of β2 receptors predominates, whereas at high doses, α1-mediated vasoconstriction overcomes the β2 effect and increases systemic vascular resistance. The overall clinical effects of vasoactive agents depend not only on the outcome of direct adrenergic receptor stimulation, but also on the reflex response of homeostatic forces. For example, stimulation of β1-adrenergic receptors by norepinephrine would be expected to cause an increase of heart rate; however, norepinephrine-mediated α1-adrenergic stimulation induces a reflex increase of vagal tone that cancels out its positive chronotropic effects. Commonly used drugs with vasopressor activity are dopamine, epinephrine, norepinephrine, phenylephrine, and ephedrine. Agents with positive inotropic activity that are useful for the treatment of hypotension include dobutamine, dopamine, epinephrine, and isoproterenol. When administered intravenously, the effects of dopamine are mediated by dose-dependent stimulation of dopaminergic and adrenergic receptors, and by stimulation of norepinephrine release from nerve terminals. At low doses (less than 5 μg/kg/min), dopamine predominantly stimulates dopaminergic receptors in renal, mesenteric, and coronary vessels with minimal adrenergic effects.

The generic product will be approved if the bioequivalence testing ranges from 80% to 125% of the values for the reference drug (diferences no >20% lower or 25% higher) buy cheap rocaltrol 0.25 mcg online. Approved order 0.25 mcg rocaltrol with amex, patented products must not vary more than ±10%; therefore buy rocaltrol 0.25 mcg overnight delivery, a generic oral contraceptive could contain only 70% of the standard dose purchase 0.25 mcg rocaltrol amex. However, we should hasten to point out that there has been no evi- dence or even anecdotal suggestions that generic oral contraceptives have reduced efcacy or cause more side efects such as breakthrough bleeding. Off-Label Uses of Steroid Contraception Steroid contraception is ofen used for noncontraceptive purposes. The list is long, including treatment of acne, dysmenorrhea, heavy or irregular vaginal bleeding, menses-associated mood changes, the polycystic ovary syndrome, and endometriosis. For most of the oral contraceptive’s 50-year history, all of these have been “of-label” applications, but recently pharma- ceutical companies have conducted trials to obtain label “indications” to use in advertising directed to both clinicians and consumers. Because these trials usually compare a product to a placebo or just to another contraceptive formulation, the studies do not reveal whether the product receiving approval for an “indication” is really better than others. Prices and formularies restrict patient access to the full range of oral contraceptives96; therefore, clinicians must make judgments by comparing fndings from unrelated studies and experience to decide which A Clinical Guide for Contraception pill to use for a specifc purpose in an individual patient. In most cases, as we will emphasize, it is unlikely that there are major diferences among similar products. Potency For many years, clinicians, scientists, medical writers, and even the phar- maceutical industry attempted to assign potency values to the various progestational components of oral contraceptives. In the past, animal assays, such as the Clauberg test (endometrial change in the rabbit) and the rat ventral prostate assay, were used to determine progestin potency. Although these were considered acceptable methods at the time, a better understanding of steroid hor- mone action and metabolism and a recognition that animal and human responses difer have led to greater reliance on data collected from human studies. Historically, this has been a confusing issue because publications and experts used potency ranking to provide clinical advice. Oral contraceptive progestin potency is no longer a consideration when it comes to prescribing oral contraception, because the potency of the various progestins has been accounted for by appropri- ate adjustments of dose. In other words, the biologic efect (in this case the clinical efect) of the various progestational components in current low-dose oral contraceptives is approximately the same. The potency of a drug does not determine its efcacy or safety, only the amount of a drug required to achieve an efect. Clinical advice based on potency ranking is an artifcial exercise that has not stood the test of time. Tere is no clinical evidence that a particu- lar progestin is better or worse in terms of particular side efects or clinical responses. Tus, oral contraceptives should be judged by their clinical char- acteristics: efcacy, side efects, risks, and benefts. Our progress in lowering the doses of the steroids contained in oral contraceptives has yielded prod- ucts with little serious diferences. Mechanism of Action The combination pill, consisting of estrogen and progestin components, prevents ovulation by inhibiting gonadotropin secretion via an efect on both pituitary and hypothalamic centers. It provides stability to the endometrium so that irregular shedding and unwanted breakthrough bleeding can be minimized; and the presence of estrogen is required to potentiate the action of the progestational agents. The mechanism for this action is probably estrogen’s efect in increasing the con- centration of intracellular progestational receptors. Terefore, a minimal pharmacologic level of estrogen is necessary to maintain the efcacy of the combination pill. Because the efect of a progestational agent will always take precedence over estrogen (unless the dose of estrogen is increased many, many fold), the endometrium, cervical mucus, and perhaps tubal function refect pro- gestational stimulation. The progestin in the combination pill produces an endometrium that is not receptive to ovum implantation, a decidualized bed with exhausted and atrophied glands. It is possible that progestational infuences on secretion and peristalsis within the fallopian tubes provide additional contraceptive efects. Even if there is some ovarian follicular activity (espe- cially with the lowest dose products), these actions serve to ensure good contraceptive efcacy. Indeed, careful review of failures suggests that pregnancies usually occur because initiation of the next cycle is delayed allowing escape from ovarian sup- pression. For this reason, the 28-day pill package, incorporating seven pills that do not contain steroids, is a very useful aid to ensure adherence to the necessary schedule. Even better, the use of extended regimens or continuous dosing ofers the potential to minimize, if not eliminate, pill failures. The most prevalent problems that can be identifed associated with appar- ent oral contraceptive failures are vomiting and diarrhea. The contraceptive efectiveness of the new progestin oral contraceptives, multiphasic formulations, and lowest estrogen dose products are unequivo- cally comparable with older low-dose (<50 mg estrogen) and higher dose monophasic combination birth control pills. Trombin is generated from prothrombin by factor Xa in the presence of factor V, calcium, and phospholipids. Protein C and protein S are two other major inhibitors of coagulation and are also vita- min K-dependent. The most common inher- ited causes of venous thromboembolism are the factor V Leiden mutation, followed distantly by a mutation in the prothrombin gene. One of the three cleavage sites in factor V is the precise site of a mutation known as the factor V Leiden A Clinical Guide for Contraception mutation that substitutes glutamine instead of arginine at this site (adenine for guanine at nucleotide 1691 in the gene). Heterozygotes for the factor V Leiden mutation have an 8-fold increased risk of venous thrombosis, and homozygotes have an 80-fold increased risk, and this risk is further enhanced by oral contraceptive use. The highest prevalence (3% to 4% of the general population) of factor V Leiden is found in Europeans, and its occurrence in populations not of European descent is very rare, perhaps explaining the low frequency of thromboembolic dis- ease in Africa, Asia, and in Native Americans. The next most common inherited disorder afer the factor V Leiden mutation is a mutation, a guanine to adenine change, in the gene encoding prothrombin. Tere is no evidence of an increase in risk of cardiovascular disease among past users of oral contraception. Instead, the fndings have been consistent with the contention that car- diovascular disease due to oral contraception is secondary to acute efects, specifcally estrogen-induced thrombosis, a dose-related event. Venous Thromboembolism Older epidemiologic evaluations of oral contraceptives and vascular disease indicated that venous thrombosis was an efect of estrogen, limited to current users, with a disappearance of the risk by 3 months afer discontinuation. In the frst years of oral contraception, the available products, containing 80 and 100 mg ethinyl estradiol (an extremely high dose), were associated with a 6-fold increased risk of venous thrombosis. Two forces, therefore, were at work simultaneously to bring greater safety to women utilizing oral contraception: (1) the use of lower dose formulations, and (2) the avoidance of oral contraception by high-risk patients. Because of these two forces, the Puget Sound study in the United States documented a reduction in venous thrombosis risk to 2-fold. A Clinical Guide for Contraception The Transnational Study on Oral Contraceptives and the Health of Young Women analyzed 471 cases of deep vein thrombosis and/or venous throm- boembolism from the United Kingdom and Germany. Comparing users of desogestrel and gestodene products to users of second- generation oral contraceptives, the risk of venous thromboembolism was 1. A third major study was from Boston University, but the data were derived from the General Practice Research Database, a computerized sys- tem involving the general practitioners in the United Kingdom. Over a 3-year period, they collected a total of 15 unexpected idiopathic cardiovascular deaths in users of these products, a nonsignifcant change, and no diference in the risk comparing desogestrel and gestodene with levonorgestrel. The risk esti- mates for venous thromboembolism (adjusted for smoking and body size) were about two times greater for desogestrel and for gestodene, compared with levonorgestrel uses. In an updated analysis from this same group and database, the fndings were unchanged, except that smoking was found to be a risk factor for venous thromboembolism. In Denmark, Lidegaard and colleagues performed a hospital-based, case- control study of women with confrmed diagnoses of venous thromboem- bolism in 1994 and 1995 (in Denmark, all women with this diagnosis are hospitalized, and therefore, very few, if any, cases were missed). Because there were more short-term users of the new progestins and more long-term users of the older progestins, adjustment for duration of use resulted in no signifcant difer- ences between the diferent types of progestins. Notably, conditions not associ- ated with an increased risk of venous thromboembolism included smoking, migraine, diabetes, hyperlipidemia, parity, or age at frst birth. Tere was Oral Contraception still insufcient strength in this study to establish the absence or presence of a dose-response relationship comparing the 20 mg estrogen dose to higher doses; however, a 5-year update reported the following useful information:147 ■ The risk of venous thrombosis associated with current use of oral con- traceptives declined with increasing duration of use. Case-control studies using cases of venous thromboembolism derived from the computer records of general practices in the United Kingdom concluded that the increased risk associated with oral contraceptives was the same for all types, and that the pattern of risk with specifc oral contraceptives sug- gested confounding because of “preferential prescribing” (defned later). A similar analysis based on 42 cases from a German database again found no diference between new progestin and older progestin oral contraceptives. An assessment of the incidence of venous thromboembolism in the United Kingdom before and afer the decline in third-generation progestin use could detect no impact on the statistics (neither an increase nor a decrease). Statisti- cal analysis with adjustment for duration of use in 105 cases who were frst-time users could fnd no diferences between second- and third-generation products. A similar reanalysis of the United Kingdom General Practice Database could demonstrate no diference between diferent oral contraceptive formulations. Former users discontinue oral contraceptives for a variety of reasons, and ofen are switched to what clinicians perceive to be “safer” products, a practice called “preferential prescribing.

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Diagnosis can sometimes be easy erally incomplete there is external genital ambiguity of but is usually not so purchase rocaltrol 0.25 mcg without a prescription. The orifice at the vestibule varying degrees order rocaltrol 0.25mcg with mastercard, the uterus generic 0.25 mcg rocaltrol otc, tubes and upper vagina may be clearly visible but more often careful search being absent since the production of Müllerian‐inhibit­ is necessary to locate it cheap rocaltrol online amex, if it can be seen at all. Cystoscopy and urethroscopy may be necessary to the decision on the sex of rearing will depend on the establish if normal ureteric openings exist in the blad­ degree of masculinization of the external genitalia but der. Radiological study may be helpful by indicating a the female role is often the chosen one. The identification of the will involve the help of a urological surgeon, and precise enzyme defect can be difficult, but may be partial nephrectomy and ureterectomy or reimplan­ approached through human chorionic gonadotrophin tation of the ectopic ureter into the bladder may be stimulation of the gonads and measurement of various undertaken. Note that 3β‐dehydrogenase (labelled 2) is active at two points, as are 17‐hydroxylase (labelled 3), 17,20‐desmolase (labelled 4), 21‐hydroxylase (labelled 6) and 11‐hydroxylase (labelled 7). The formation of the artificial vagina Mullerian duct formation, regression and differentiation. Psychological distress in women with uterovaginal 15 Fedele L, Bioanchi S, Zanconato G et al. Congenital Malformations of the Sanfilippo J, Lara‐Torre E, Edmonds K, Templeman C (eds) Female Genital Tract. Therefore, it is very are the first steps in the management of a patient pre­ important to have a good basic knowledge of how the senting with gynaecological symptoms. Physical properties and settings the introduction of ultrasound has changed the approach to many disorders in gynaecology. It has rede­ the term ‘ultrasound’ describes sound waves of such a fined the diagnostic criteria and management of prob­ high frequency that they cannot be heard by humans. This results in improved resolution, but with the bleeding or infertility, enabled the accurate characteriza­ trade‐off of poorer penetration. As a result such probes tion of pelvic masses and allowed significant advances in need to be used close to the area of interest. However, improvements in probe design have led to In this chapter, we focus on practical guidance in per­ them being significantly more adaptable than in the forming gynaecological ultrasound and discuss the role past [2]. Besides adjusting the frequency, it is also of different imaging modalities in common clinical con­ important to change the focus of the ultrasound beam ditions encountered in gynaecological practice. Harmonic imaging can further Ultrasound techniques improve image quality, especially in cystic lesions (e. Once the area of interest has been An ultrasound examination of the pelvis is one of the located, the image can be magnified in order to obtain most common procedures in gynaecology, with most maximum detail. This is helpful in cost and less time‐consuming compared to other maging visualizing normal anatomy (e. Another important advantage is its possibil­ ries), defining the origin of structures and, if used in ity for dynamic evaluation, which helps in understanding a standardized way, characterizing pathology [1,3–6]. This is helpful for the characterization of that the quality of ultrasound imaging, more than in congenital uterine abnormalities and for the delinea­ other imaging techniques, not only relies on the equip­ tion of the endometrial–myometrial junction to assess ment but also on its settings as well as on the experience acquired uterine pathology [7,8]. Recent consensus documents have outlined proposed terminol­ Transvaginal ultrasonography is the method of choice, as ogy to describe the endometrium and myometrium, with it results in the best image quality, due to the proximity any pathology that may be present [3,6]. However, a Difficulties in assessment due to variations in uterine transabdominal scan may be required to assess the uterus position (particularly when axial) or uterine rotation in the presence of large fibroids or to evaluate the adnexa (endometriosis or adhesions) can be overcome by press­ when these are enlarged and extending beyond the level ing on the abdomen with the non‐scanning hand, or by of the pelvis. Although a full bladder can be useful for transabdominal scanning, in many cases it is not Sonohysterography required. A good technique is to identify the femoral vessels and follow these upwards to the iliac vessels Sonohysterography is the instillation of fluid through a and finally to the bifurcation of the aorta. An ovarian catheter into the uterine cavity to act as a negative con­ mass and any lymphadenopathy present can be assessed trast agent to outline any focal intra‐cavity pathology. In saline instillation, aware that an examination of the abdomen does not a neonatal suction catheter may be used, although back­ stop in the pelvis and the examiner should be familiar flow may necessitate the use of a more expensive balloon with the normal appearances of the organs of the upper catheter to obtain a more stable filling of the uterine cav­ abdomen and the likely sites of metastatic disease in ity. The higher viscosity of gel results in a smaller instilla­ the event of gynaecological malignancy. These might tion volume, which makes the procedure better tolerated include the peritoneum, lymph nodes around the large by patients compared with saline instillation [11]. Ascites may be Moreover, transtubal spillage is less likely to occur and present in the upper abdomen. A further natal suction catheter (2mm) is sufficient, but it might marker of serious intra‐abdominal bleeding is the pres­ be helpful to warm the gel to 37°C to promote flow ence of fluid in Morrison’s pouch between the liver and through the catheter. It might be prudent in fertile women to advocate con­ the uterus should be assessed in the sagittal plane, traception during the cycle when the sonohysterography including detailed evaluation of the cervix, the body of procedure is planned, and some examiners advise that the uterus, the fundus and the endometrial cavity. Views prophylactic antibiotics should be administered prior to obtained in the transverse plane may help in defining the the procedure in all potentially fertile women to avoid location of focal pathology. There is a large amount of data to suggest that plane including both endometrial layers (double endo­ sonohysterography is comparable to hysteroscopy for metrial thickness), is an important assessment. A sonographic exami­ regarding the endometrial findings, sonohysterography nation in this population should preferably be performed is always a good option to consider. Hysterosalpingo‐contrast sonography and hysterosalpingo‐foam sonography the gold standard test to assess tubal patency is laparo­ scopic chromoperturbation with methylene blue. However, this procedure is associated with the risks of laparoscopy under general anaesthesia. Therefore, as a less invasive radiography technique, X‐ray hysterosal­ pingography has been applied for decades in the diag­ nostic work‐up of the patient presenting with infertility [15]. On this image, there is fallopian tubes during hysterosalpingo‐contrast sonog­ visible bilateral patency through the isthmic and intramural raphy [16]. More recently, hysterosalpingo‐foam acquire tissue diagnosis in the management of advanced sonography was introduced, using ‘gel foam’, with advan­ or recurrent gynaecological tumours or when pelvic tageous physical properties compared with saline [18] metastatic disease from another primary origin is sus­. A similar approach with an aspiration needle connected to a syringe or vacuum container allows the drainage of symptomatic Ultrasound‐guided procedures pelvic cysts, on condition that there is no suspicion of Ultrasound can guide different invasive procedures in malignancy. Besides the well‐known application in simple ovarian cysts or tubo‐ovarian abscesses in pelvic reproductive medicine for oocyte retrieval, there is inflammatory disease [23]. In abnormal uterine bleeding, the usefulness of an ultrasound evaluation of the endome­ ● A good basic knowledge of the technical features of trial thickness to detect pathology is much less obvious the ultrasound machine is important, as quality of in premenopausal women compared with postmenopau­ ultrasound imaging relies on the settings of the device. In certain conditions, blood vessels can be visualized on colour Doppler a transabdominal or transrectal approach can be imaging, the so‐called ‘pedicle artery’ sign, which is considered. Fluid instillation should be considered if the can improve the visualization of structures or aid in the endometrium is not well visualized on unenhanced evaluation of adhesions or site‐specific tenderness. Imaging in common gynaecological conditions Abnormal uterine bleeding Over recent years transvaginal ultrasonography has significantly improved our ability to accurately manage patients with abnormal uterine bleeding. From these causes, imaging methods can only confirm or exclude anatomical abnormalities, i. However, these might or might not be the cause of the bleeding problem, as they may also be found in asymptomatic women. In the large majority of premeno­ pausal women, abnormal uterine bleeding is associated. Myometrial lesions with a large diameter are the most likely to result in abnormal uterine bleeding (e. At ultrasonography, fibroids are signal intensity that closely resembles a leiomyoma, or a generally well‐circumscribed round lesions within the mass with focally infiltrative margins. Detection of myometrium or attached to it, often showing shadows at scattered foci of haemorrhage or necrosis can suggest the edge of the lesion and/or internal fan‐shaped shad­ the diagnosis of uterine leiomyosarcoma. On colour or power Doppler finding in uterine leiomyosarcomas is the absence of imaging, circumferential flow around the lesion is often calcifications [32]. However, some fibroids do not exhibit should discourage the clinician to select the patient for such typical features [6,29]. Three‐dimensional ultra­ minimally invasive surgery with tissue morcellation in sound may help in localizing the fibroid with respect to order to avoid the fragmentation and intra‐abdominal the uterine cavity. It is often very challenging to discriminate between Another differential diagnostic difficulty with fibroids fibroids and malignant tumours of mesenchymal origin, relates to their discrimination from adenomyosis. The trial asymmetry, cystic areas within the myometrium, vessels are of unequal size and exhibit irregular branching. More recently, the metrium is not measurable or not completely visible, it presence of an irregular or interrupted endometrial– should be considered abnormal until proven otherwise. These principally relate to how con­ idly, especially with the addition of new functional tech­ fident the examiner is that he or she is not looking at a niques over the past decade, such as diffusion‐weighted solid ovarian lesion. The demonstration of two normal sion and the presence of cervical invasion with similar ovaries is the obvious solution to this problem. High‐risk endometrial cancer more often Postmenopausal bleeding has a mixed or hypoechoic echogenicity, a higher colour the causes of abnormal premenopausal uterine bleed­ score, and multiple vessels with multifocal origin, ing, such as polyps and uterine sarcomas, can be found in whereas less‐advanced tumours are more often hypere­ postmenopausal women as well.

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Carbapenems Carbapenems are synthetic β-lactam antibiotics that differ in structure from the penicillins in that the sulfur atom of the thiazolidine ring (ure 29 purchase rocaltrol 0.25mcg with mastercard. Antibacterial spectrum Imipenem resists hydrolysis by most β-lactamases order rocaltrol 0.25 mcg visa, but not the metallo-β-lactamases purchase rocaltrol 0.25 mcg with mastercard. This drug plays a role in empiric therapy because it is active against β-lactamase–producing gram-positive and gram-negative organisms order generic rocaltrol from india, anaerobes, and P. Meropenem is known to reach therapeutic levels in bacterial meningitis even without inflammation. Imipenem undergoes cleavage by a dehydropeptidase found in the brush border of the proximal renal tubule. Compounding imipenem with cilastatin protects the parent drug from renal dehydropeptidase and, thus, prolongs its activity in the body. High levels of imipenem may provoke seizures; however, the other carbapenems are less likely to do so. While those with true penicillin allergy should use carbapenems cautiously, the cross-reactivity rate seen in studies is very low (less than 1%). Monobactams the monobactams, which also disrupt bacterial cell wall synthesis, are unique because the β-lactam ring is not fused to another ring (ure 29. Aztreonam is relatively nontoxic, but it may cause phlebitis, skin rash, and, occasionally, abnormal liver function tests. This drug has a low immunogenic potential, and it shows little cross-reactivity with antibodies induced by other β-lactams. Thus, this drug may offer a safe alternative for treating patients who are allergic to other penicillins, cephalosporins, or carbapenems. The β-lactamase inhibitors are, therefore, formulated in combination with β- lactamase–sensitive antibiotics, such as amoxicillin, ampicillin, and piperacillin (ure 29. Its niche for use is in the treatment of resistant Enterobacteriaceae and multidrug-resistant Pseudomonas aeruginosa. Ceftazidime-avibactam has minimal activity against Acinetobacter as well as anaerobic and gram-positive organisms. Both of these combinations are indicated for the treatment of intra-abdominal infections (in combination with metronidazole) and for the management of complicated urinary tract infections. Given the extensive antimicrobial activity, ceftolozane–tazobactam and ceftazidime–avibactam are reserved for the treatment of infections due to multidrug-resistant pathogens. Carbapenem/β-lactamase inhibitor combination Meropenem-vaborbactam is a combination of a carbapenem and a β-lactamase inhibitor. It is approved for the treatment of complicated urinary tract infections including pyelonephritis. This combination agent has activity against Enterobacteriaceae producing a broad spectrum of β-lactamases, except metallo-β-lactamases. Following cell entry, it binds to peptidoglycan precursors, disrupting polymerization and cross-linking required for maintenance of cell wall integrity. Therefore, monitoring of creatinine clearance is required to optimize exposure and minimize toxicity. Optimal cure rates are observed when trough concentrations are maintained between 10 and 20 mcg/mL. Common adverse events include nephrotoxicity, infusion-related reactions (red man syndrome and phlebitis), and ototoxicity. Resistance is driven by alterations in binding affinity to peptidoglycan precursors. Lastly, vancomycin has poor absorption after oral administration, so use of the oral formulation is limited to the management of Clostridium difficile infection in the colon. The lipoglycopeptides maintain a spectrum of activity similar to vancomycin, affecting primarily staphylococci, streptococci, and enterococci. Because of structural differences, they are more potent than vancomycin and may have activity against vancomycin-resistant isolates. The lipid tail is essential in anchoring the drug to the cell walls to improve target site binding. In combination, these actions improve activity and minimize selection of resistance. Prior to initiation, assessment of renal function, pregnancy status, and current medications is needed to ensure safe administration. Oritavancin and telavancin are known to interfere with phospholipid reagents used in assessing coagulation. Daptomycin is indicated for the treatment of complicated skin and skin structure infections and bacteremia caused by S. Efficacy of treatment with daptomycin in left-sided endocarditis has not been demonstrated. Additionally, daptomycin is inactivated by pulmonary surfactants; thus, it should never be used in the treatment of pneumonia. It blocks cell wall synthesis by inhibiting the enzyme enolpyruvyl transferase, a key step in peptidoglycan synthesis. Due to its unique structure and mechanism of action, cross-resistance with other antimicrobial agents is unlikely. Fosfomycin is rapidly absorbed after oral administration and distributes well to the kidneys, bladder, and prostate. The drug is excreted in its active form in the urine and maintains high concentrations over several days, allowing for a one-time dose. Polymyxins the polymyxins are cation polypeptides that bind to phospholipids on the bacterial cell membrane of gram-negative bacteria. They have a detergent-like effect that disrupts cell membrane integrity, leading to leakage of cellular components and cell death. Polymyxins are concentration-dependent bactericidal agents with activity against most clinically important gram-negative bacteria, including P. However, alterations in the cell membrane, lipid polysaccharides allow many species of Proteus and Serratia to be intrinsically resistant. Only two forms of polymyxin are in clinical use today, polymyxin B and colistin (polymyxin E). Polymyxin B is available in parenteral, ophthalmic, otic, and topical preparations. The use of these drugs has been limited due to the increased risk of nephrotoxicity and neurotoxicity (for example, slurred speech, muscle weakness) when used systemically. However, with increasing gram-negative resistance, they are now commonly used as salvage therapy for patients with multidrug-resistant infections. Careful dosing and monitoring of adverse effects are important to maximize the safety and efficacy of these agents. Incision and drainage were performed on the abscess, and cultures revealed methicillin-resistant Staphylococcus aureus. Which is the most appropriate treatment option for once-daily outpatient intravenous therapy in this patient? Myalgias and rhabdomyolysis have been reported with daptomycin therapy and require patient education and monitoring. Which of the following regimens is most appropriate for empiric coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa in this patient? Daptomycin is inactivated by pulmonary surfactant and should not be used for pneumonia. He is taken to the operating room for surgery, and postsurgical cultures reveal Escherichia coli and Bacteroides fragilis, susceptibilities pending. Which of the following β-lactams is the most appropriate choice for gram-negative coverage of this patient’s urinary tract infection? Based on the severity of the allergic reaction, aztreonam is the choice of all the β-lactams. Although cross-reactivity with cephalosporins and carbapenems is low, the risk rarely outweighs the benefit in these cases. A single treatment with penicillin is curative for primary and secondary syphilis. No antibiotic resistance has been reported, and it remains the drug of choice unless the patient has a severe allergic reaction.

The increased frequency of thromboembolic disease in pregnancy may be attributable to a hypercoagulable state along with venous stasis cheap 0.25mcg rocaltrol free shipping. The activity of plasminogen activator inhibitor types 1 and 2 cheap 0.25 mcg rocaltrol visa, which are inhibitors of fibrinolysis buy generic rocaltrol 0.25mcg online, also increases [8] order rocaltrol cheap online. Venous stasis may occur because of a hormonally induced dilation of capacitance veins and uterine pressure on the inferior vena cava [9]. The usefulness of the serum D-dimer levels in diagnosing thromboembolic disease in pregnancy is limited because D- dimer levels are increased during normal pregnancy, with levels increasing as gestation progresses and peaking at delivery and in the early postpartum period [10]. Fetal exposure to radiation during imaging studies can be minimized by abdominal shielding and using brachial access. Suggested risk factors include older maternal age (mean, 32 years), multiparity (88% of cases), amniotomy, cesarean section, abruptio placentae, insertion of intrauterine fetal or pressure monitoring devices, and term pregnancy in the presence of an intrauterine device [16]. Amniotic fluid enters the maternal circulation through one of three ports: endocervical veins, uterine tears (small tears may occur in the lower uterine segment as a part of normal labor), and uterine injury secondary to iatrogenic manipulation, such as cesarean section, insertion of monitoring devices, or membrane rupture. Elevation of the pulmonary capillary wedge pressure and reduction in cardiac output and left ventricular stroke work index have been documented [17]. Acute left heart failure contributes to the development of pulmonary edema, which leads to dyspnea, tachypnea, and cyanosis. Other factors potentially contributing to pulmonary edema include cardiodepressive humoral factors from the amniotic fluid, vigorous fluid resuscitation, increased permeability pulmonary edema, and hypoxia causing myocardial ischemia [18]. Other complications, such as acute renal failure and signs of central nervous system injury, are probably secondary to hypotension and hypoxemia. Prodromal symptoms, such as vomiting and shivering, are nonspecific and frequently associated with otherwise uneventful deliveries. Cardiac echo may show decreased left ventricular function or echodense material in the right atrium or right ventricular outflow tract [17]. The perinatal mortality from national registries ranges from 7% to 38%, with up to 50% of the surviving children experiencing permanent neurologic injury [18]. Venous Air Embolism Venous air embolism is the entrainment of air into the venous system where it then travels to the right ventricle and the pulmonary circulation. Venous air embolism has been described during normal labor, delivery of patients with placenta previa, criminal abortions using air, and insufflation of the vagina during gynecologic procedures. Presumably, the subplacental venous sinuses are the sites of air entry when antepartum or peripartum air embolism occurs. The clinical presentation of venous air embolism varies according to the volume and speed of air entrainment into the vascular circulation. The classic sign associated with air embolism is the mill wheel murmur, which is audible over the precordium [19]; a drum-like or bubbling sound may also be heard. Electrocardiographic evidence of ischemia, right heart strain, and arrhythmias have been described, and metabolic acidosis, presumably caused by lactic acid production, may be present [19] (see Chapter 198). Neurologic symptoms develop as a consequence of cerebral hypoperfusion from cardiovascular collapse and from paradoxic embolization if a patent foramen ovale is present [19]. Based on data from surgical procedures, precordial Doppler ultrasound can be used for surveillance of air embolism by detection of alterations in the ultrasonic pattern caused by the embolism and is able to detect as little as 0. The volume of air that is likely to be lethal seems to vary with the rate of infusion and patient position. A bolus of 200 to 300 mL of air or 3 to 5 mL per kg has been reported to be the lethal dose in humans [19,20]. It is thought that entrapment of air bubbles in the pulmonary circulation leads to activation of complement, neutrophils, and platelets, resulting in mediator release, protease activation, oxidant stress, and endothelial injury [19]. Aspiration of Gastric Contents Aspiration of acidic gastric contents into the tracheobronchial tree was first described in 1946 by Mendelson [21] in women during labor and delivery. Maternal deaths from pulmonary aspiration have been steadily declining as a result of changing anesthesia practices, including a shift to regional anesthesia from general anesthesia for delivery [22]. At term, several factors contribute to an increased risk of aspiration of stomach contents: (a) increased intragastric pressure caused by external compression by the gravid uterus, (b) progesterone-induced relaxation of the lower esophageal sphincter, (c) delayed gastric emptying during labor, (d) supine position, and (e) analgesia-induced decreased mental status and decreased vocal cord closure [23]. The pulmonary pathophysiologic consequences of gastric aspiration are a consequence of the acidity and the particulate content of the gastric contents and the risk of bacterial superinfection. An inflammatory response is also triggered by the acid aspiration, leading to an increase in alveolar permeability with a loss in lung compliance and a decrease in ventilation–perfusion matching [23]. Aspiration of smaller volumes may go unnoticed clinically until 6 to 8 hours later, when tachypnea, tachycardia, hypoxemia, hypotension, bronchospasm, and production of frothy, pink sputum are noted in association with diffuse opacities on chest radiography. The clinical course may follow one of three patterns: (a) rapid improvement during 4 to 5 days, (b) initial improvement followed by deterioration caused by supervening bacterial pneumonia, and (c) early death as a result of intractable hypoxia [23]. Predictors of poor outcome include low pH, large volume, and a greater amount of particulate content of the aspirate. The bacterial pathogens in this setting are usually oropharyngeal anaerobes, although the longer the patient is in the hospital before clinical development of pneumonia, the greater the likelihood of facultative, Gram-negative bacillary, and Staphylococcus aureus infections [23]. The maternal mortality rate from pneumonia has decreased from 20% to 3% since the advent of antibiotics [24]. The major factors in improving fetal and maternal outcome seem to have been earlier presentation and prompt institution of antibiotic therapy. Although pneumonia rarely progresses to respiratory failure, it is advisable to assess maternal oxygenation in all cases of maternal pneumonia. The spectrum of organisms to consider is similar to that in the nonpregnant population; the most common organisms are Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae. These particular infections can be virulent in the pregnant patient because of alterations in the immune status. Specifically, during pregnancy, there is a decreased lymphocyte proliferative response, a decrease in the natural killer cell activity, and a decrease in the number of helper T4 cells [24]. Fortunately, the impairment in maternal immune response is mild, and the increase in maternal morbidity is small. In the influenza pandemics of 1918, 1957, and 2009, an excess incidence of influenza pneumonia was noted among pregnant women. A 50% incidence of influenza pneumonia and an overall mortality of 27% for influenza in pregnancy were found in 1918 [26]. In the 1957 pandemic, several studies noted that 50% of deaths from influenza in women of childbearing age were in pregnant patients [26]. Autopsy reports noted that the cause of death in pregnant women was respiratory insufficiency caused by fulminant influenza pneumonia, rather than secondary bacterial infection, the more common cause of death in nonpregnant influenza patients. The pandemic in 2009 was attributed to influenza A(H1N1)pdm09 virus, and the Centers for Disease Control and Prevention data from 2009 to 2010 revealed that 12% of pregnancy- related deaths were attributed to influenza A(H1N1)pdm09 [27]. In addition, higher rates of miscarriage, preterm birth, and small for gestational age babies have been noted in mothers infected with influenza [26]. The typical symptoms of influenza include cough, fever, sore pharyngitis, rhinorrhea, diarrhea, headache, and myalgias [26]. The introduction of the varicella vaccine in 1995 has led to this lower incidence because of high rates of varicella-zoster virus seropositivity among adults in the United States [28]. Varicella pneumonia is estimated to complicate 10% to 20% of maternal infections, although a study of a large database cohort found the incidence of maternal varicella pneumonia to be 2. Furthermore, the mortality rate for maternal varicella pneumonia has declined significantly since the development of antiviral therapy and institution of varicella vaccination. Historically, the mortality rate for maternal varicella pneumonia was 41%, but, in the era of antiviral therapy and vaccination, the mortality rate is now estimated to be 3% to 14% [28]. Cigarette smoking appears to be an important risk factor in the progression of varicella into pneumonia [24]. Generalized varicella-zoster infections may also be associated with hepatitis, myocarditis, nephritis, thrombocytopenia, and adrenal hemorrhage [24]. Varicella during pregnancy can lead to intrauterine infection, which can result in prematurity, spontaneous abortion, and stillbirth [24]. In the absence of dissemination, herpes zoster does not appear to be associated with significant maternal morbidity or evidence of fetal infection [28]. Symptoms of fever, chills, rigors, headache, malaise, and myalgias develop 2 to 7 days after exposure. Maternal Coccidioidomycosis immitis infections are rare, with less than 1 case in every 1,000 pregnancies. Case reports of cryptococcosis, blastomycosis, and sporotrichosis in pregnancy are rare enough to suggest that there may be no increased susceptibility to these infections [30]. Diagnosis is sometimes difficult because sputum is positive in less than 40% of cases, and complement fixation titers may be low [30].

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Doripenem buy rocaltrol 0.25mcg free shipping, meropenem buy 0.25mcg rocaltrol with amex, and ertapenem have somewhat better activity against gram-negative pathogens (except Pseudomonas for ertapenem buy rocaltrol 0.25 mcg fast delivery, as described later in this subsection) purchase rocaltrol 0.25 mcg free shipping. They have static activity against penicillin-sensitive enterococci; however, many penicillin-resistant strains are also resistant to carbapenems. Resistance in gram- negative bacilli is most often secondary to loss of an outer membrane protein called D2 that is required for intracellular penetration of the carbapenems. Increasing numbers of gram-negative strains can also produce β-lactamases called carbapenemases that can hydrolyze these drugs. Very broad cidal activity for aerobic and anaerobic gram-positive and gram-negative bacteria. Imipenem, doripenem, and meropenem are useful for empiric therapy of suspected mixed aerobic and anaerobic infection or a severe nosocomial infection, pending culture results. Imipenem, doripenem, and meropenem can be used as empiric therapy for sepsis, and they are particularly useful if polymicrobial bacteremia is a strong possibility. They can also be used to treat severe intra-abdominal infections and complicated pyelonephritis. Infections attributable to gram-negative bacilli resistant to cephalosporins and aminoglycosides may be sensitive to imipenem, doripenem, or meropenem. Imipenem is not recommended for this purpose because of its propensity to cause seizures. In general, imipenem, doripenem, and meropenem should be reserved for the seriously ill patient or the patient infected with a highly resistant bacterium that is sensitive only to this antibiotic. Ertapenem has a longer half-life and can be given just once daily, making it a useful agent for home intravenous therapy. It is recommended for complicated intra- abdominal infections, postpartum and postoperative acute pelvic infections, and complicated soft tissue infections. Because the carbapenems are extremely broad-spectrum agents, they kill nearly all normal flora. These agents have a characteristic 6-member ring with amino-group substitutions, and they are highly soluble in water. At neutral pH, they are positively charged, and this positive charge contributes to their antibacterial activity. Their positive charge also causes aminoglycosides to bind and to become inactivated by β-lactam antibiotics. Therefore, aminoglycosides should never be in the same solution with β-lactam antibiotics. These agents are among the most toxic drugs prescribed today, and they should be avoided whenever safer alternative antibiotics are available (Table 1. Incidence is higher in a) elderly individuals, b) patients with preexisting renal disease, c) patients with volume depletion and hypotension, and d) patients with liver disease. Higher incidence of nephrotoxicity with coad-ministration of vancomycin, cephalosporins, clindamycin, piperacillin, foscarnet, or furosemide. The loss of high-frequency hearing and vestibular dysfunction resulting from ototoxicity is often devastating for elderly individuals. Injury to the proximal convoluted tubules of the kidney leads to a reduction in creatinine clearance. The brush border cells of the proximal tubule take up aminoglycosides by endocytosis, and intracellular entry is associated with cell necrosis. Aminoglycosides cause significant reductions in glomerular filtration in 5-25% of patients. Patient characteristics associated with an increased risk of nephrotoxicity include older age, preexisting renal disease, hepatic dysfunction, volume depletion, and hypotension. Reexposure to aminoglycosides increases risk, as do the use of larger doses, more frequent dosing intervals, and treatment for more than 3 days. The risk of renal failure is also associated with coadministration of vancomycin, amphotericin B, clindamycin, piperacillin, cephalosporins, foscarnet, or furosemide. Because renal tubular cells have regenerative power, renal dysfunction usually reverses on discontinuation of the aminoglycoside. Because aminoglycosides are primarily renally cleared, aminoglycoside serum levels are useful for detecting worsening renal function. Trough aminoglycoside serum levels often rise before a significant rise in serum creatinine can be detected. Aminoglycosides enter the inner ear fluid and damage outer hair cells important to the detection of high-frequency sound. Loss of high-frequency hearing occurs in 3-14% of patients treated with aminoglycosides. The risk of hearing loss is greater after prolonged treatment, with most cases developing after 9 or more days of therapy. Hearing loss is irreversible and can occur weeks after therapy has been discontinued. A genetic predisposition has been observed, with certain families having a high incidence of deafness after receiving aminoglycosides. Neomycin has the highest risk of toxicity, followed in order of decreasing frequency by gentamicin, tobramycin, amikacin, and netilmicin. Concomitant use of furosemide or vancomycin and exposure to loud noises increase the risk. As compared with dosing at 8-hour intervals, once-daily dosing reduces the toxic risk. Less commonly, aminoglycosides can cause neuromuscular blockade; they should be avoided in myasthenia gravis. Given the high risk of toxicity, aminoglycosides should be used only when alternative antibiotics are unavailable. When aminoglycosides are required, the duration of therapy should be as brief as possible. Pretreatment and periodic testing of high- frequency hearing should be performed, and serum creatinine and aminoglycoside serum levels should be monitored. Therefore, to determine peak serum level, blood samples should be drawn 30 minutes after completion of the intravenous infusion. The half-life of aminoglycosides is 2-5 hours, and these agents are cleared by the kidneys. Proper dosing of aminoglycosides is more complicated than for most other antibiotics, and these agents require close monitoring. For daily multiple-dose therapy, a loading dose is first given to rapidly achieve a therapeutic serum level; maintenance doses are then administered. In the setting of renal dysfunction, dosing must be carefully adjusted, and peak and trough serum levels monitored. Once-daily aminoglycoside dosing is now the preferred therapy in nearly all instances. As compared with multidose therapy, once-daily administration reduces the concentration of the aminoglycoside that accumulates in the renal cortex and lowers the incidence of nephrotoxicity. Because aminoglycosides demonstrate concentration-dependent killing, the high peak levels achieved with this regimen increase the bactericidal rate and prolong the post-antibiotic effect. This regimen has not been associated with a higher incidence of neuromuscular dysfunction. Monitoring of serum levels is recommended for both multidose and once- daily regimens. With multidose therapy, blood for a peak level determination should be drawn 30 minutes after intravenous infusion is complete, and for a trough level, 30 minutes before the next dose. Blood for peak and trough determinations should be drawn after the third dose of antibiotic to assure full equilibration within the distribution volume. In the critically ill patient, blood for a peak level determination should be drawn after the first dose to assure achievement of an adequate therapeutic level. For once-daily dosing, trough levels need to be monitored to assure adequate clearance. Alternatively, blood for a level determination can be drawn between 6 and 14 hours, and the value applied to a nomogram to help decide on subsequent doses. In the seriously ill patient, blood for a peak level determination should also be drawn 30 minutes after completion of the infusion to assure that a therapeutic level is being achieved (for gentamicin–tobramycin, a target concentration of 16 to 24 µg/mL should be achieved). Once-daily dosing is not recommended for the treatment of enterococcal endocarditis and has not been sufficiently studied in pregnancy or in patients with osteomyelitis or cystic fibrosis. These agents kill rapidly, and the killing is concentration-dependent—that is, the rate increases as the concentration of the antibiotic increases. Aminoglycosides also demonstrate persistent suppression of bacterial growth for 1-3 hours after the antibiotic is no longer present.

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