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Because Foreign bodies order 480 mg septra with visa, such as indwelling catheters discount septra 480mg fast delivery, provide antimicrobial drug concentrations are low in bone buy septra 480 mg online, patients sites where microbes can become covered with a glycocalyx with osteomyelitis must usually be treated with antibiotics coating (bioflm) that protects them from antibiotics and for several weeks to produce a cure order septra 480 mg otc. Less commonly, hepatic insuffciency favor the entry and accumulation of weak bases (e. Antimicrobial agents can be selected on the basis of labora- Antibiotics that are eliminated by the kidneys (e. Empiric therapy may be used to treat serious infec- tions until test results are available or to treat minor upper Adverse Effect Profle respiratory and urinary tract infections because of the pre- Any antimicrobial drug can cause mild to severe adverse dictability of causative organisms and their sensitivity to effects, but the incidence of these effects varies greatly drugs. In these situations, the cost of microbial culture and among different classes of drugs, and it is important to drug sensitivity tests is usually not justifed. A few situa- and are often used to treat minor infections, including infec- tions in which combination therapy is preferable are tions in pregnant women. Fluoroquinolones and tetracy- Pharmacokinetic Properties clines are intermediate in their adverse effect profle. These include infections that are known or suspected drug for ambulatory patients would have good oral bioavail- to be caused by more than one pathogen (mixed infections), ability and a long plasma half-life so that it would need to such as intraabdominal infections caused by both aerobic be taken only once a day. Azithromycin is an example of an and anaerobic organisms derived from the intestinal tract. This is partly because the tissue concen- When antimicrobial drugs are given in combination, they trations of a drug are sometimes lower than the plasma can exhibit antagonistic, additive, synergistic, or indifferent concentration. The relationship between the plasma concen- effects against a particular microbe (Fig. For example, penicillins, which are cell wall is equal to the sum of the independent effects; synergistic synthesis inhibitors, often show additive or synergistic if the combined effect is greater than the sum of the inde- effects with aminoglycosides, which inhibit protein syn- pendent effects; and indifferent if the combined effect is thesis, against gram-negative bacilli such as P. Bactericidal tial steps in bacterial folate synthesis and have synergistic drugs are usually more effective against rapidly dividing activity against organisms that may be resistant to either bacteria, and their effect may be reduced if bacterial growth drug alone. As discussed in Chapter 41, tuberculosis is always treated If two bactericidal drugs that target different microbial with more than one drug. Comparison of several possible interactions of two 101 Drugs X and Y antimicrobial drugs combined in vitro. Curves show the results when Synergism cultures containing 105 bacteria per milliliter are incubated with no drug (control), with drug X alone, with drug Y alone, and with a 0 combination of drugs X and Y. In an antagonistic interaction, 0 3 6 9 12 the combined effect is less than the effect of either drug alone. In Hours an indifferent interaction, the combined effect is similar to the great- est effect produced by either drug alone. In a synergistic interaction, Drug(s) the combined effect is greater than the sum of the independent added effects. The invasive procedures or to prevent disease transmission to rate of mutation to a form that is resistant to two drugs is close contacts of infected persons. Recommendations for the product of the individual drug resistance rates, or about prophylaxis are summarized in Box 37-3. Because fewer than 10 organisms are usually present in a patient with tuberculosis, it is unlikely Prevention of Infection Caused that a resistant mutant will emerge during combination by Invasive Procedures therapy. These individuals are at The prevention of infections requires the sterilization of risk for developing acute bacterial endocarditis caused by diagnostic and surgical instruments, the use of disinfectants viridans streptococci and other streptococci that can be to reduce environmental pathogens in hospitals and clinics, acquired during dental, oral, or upper respiratory tract pro- and the disinfection of skin and mucous membranes before cedures and surgery. In some cases, antimicrobial drugs are drug of choice, but endocarditis can be prevented by using also administered prophylactically either to reduce the an alternative drug (e. Drugs are also used to prevent enterococci malaria in persons who are traveling to regions of the world • Aminoglycoside plus broad-spectrum penicillin against where malaria is endemic and to prevent infuenza type A gram-negative bacilli in populations at increased risk for these diseases. Prophy- • Aminoglycoside plus cephalosporin against gram-negative lactic drugs are discussed more thoroughly in subsequent bacilli chapters. Antimicrobial drugs include cell • Broad-spectrum penicillin plus chloramphenicol against wall synthesis inhibitors, protein synthesis inhibitors, Streptococcus pneumoniae metabolic and nucleic acid inhibitors, and cell mem- • Broad-spectrum penicillin plus imipenem against gram- brane inhibitors. The choice of antibiotic depends on • Combination drug therapy is generally used for the the most likely sources of bacterial pathogens during a par- treatment of mixed infections, the empiric treatment ticular procedure. The skin is the most common source of of serious infections, and the prevention of antibiotic pathogens, especially staphylococci, during most types of resistance. The gastrointestinal tract is also an important source synergistic drugs is used for the treatment of infections of pathogens when surgical procedures involve the gastroin- caused by a single microbial species. Surgery to repair contaminated wounds • Antibiotic prophylaxis is used to prevent infections (e. A cell membrane constituent that transports chemother- drugs out of mammalian and microbial cells. The continued suppression of bacterial growth after an has been removed from a bacterial culture or eliminated antibiotic has been eliminated from the body. A synergistic effect occurs (D) concentration-dependent killing when the combined effect of two drugs is greater than the (E) synergistic effect sum of their individual effects. The combined antibacterial effect of two drugs is greater nations show synergism against susceptible organisms, than the sum of their individual effects. Transferable drug resistance (B) indifference refers to the acquisition of genes conferring resistance (C) synergism from other bacteria. Most commonly this occurs by (D) supranormal bacterial conjugation and exchange of plasmids contain- (E) competition ing resistance factors. The most frequent mechanism of transferable drug are less-common mechanisms of transferring drug resistance. It is based on visualiza- (D) conjugation tion of the point of intersection between the zone of (E) mutation and selection bacterial growth inhibition and the concentration scale 5. The penicillins were the frst antibiotics to be discov- • Penicillin G ered and isolated, and their development inaugurated the • Penicillin V modern era of antimicrobial chemotherapy in the 1940s. Penicillinase-Resistant Penicillins Despite the growing problem of microbial resistance to these • Dicloxacillin drugs, they have remained one of the most widely used • Nafcillin groups of antibiotics for over 60 years. This chapter describes • Oxacillin (Bactocill) the structure and function of the bacterial cell envelope and the pharmacologic properties and clinical use of the bacterial Extended-Spectrum Penicillins cell wall inhibitors. The cell wall is much • Clavulanate (with amoxicillin as Augmentin)a thicker in gram-positive bacteria than it is in gram-negative bacteria. The envelope of each gram-negative bacterium also First-Generation Cephalosporins has an outer membrane that is not found in other types of • Cefazolin bacteria. The cell envelope components are illustrated in • Cephalexin (Keflex) Figure 38-1. Second-Generation Cephalosporins Cytoplasmic and Outer Membranes • Cefprozil The cytoplasmic membrane is a trilaminar membrane. It • Cefaclor b contains various types of transport proteins, which facilitate • Cefuroxime (Ceftin, Zinacef) the uptake of a wide variety of substrates used by bacteria, Third-Generation Cephalosporins and it also contains several enzymes required for the synthe- c sis of the cell wall. The outer membrane of gram-negative bacteria is also a Fourth-Generation Cephalosporin trilaminar membrane. It contains species-specifc forms of a • Cefepime (Maxipime) complex lipopolysaccharide and various types of protein channels called porins. One portion of lipopolysaccharide Advanced-Generation Cephalosporin (the lipid A portion) is the endotoxin responsible for • Ceftaroline (Teflaro) gram-negative sepsis. This endotoxin activates immunologic Monobactam mechanisms that lead to fever, platelet aggregation, increased • Aztreonam (Azactam) vascular permeability, and other adverse effects on tissues. Porins allow ions and other small hydrophilic molecules to Carbapenems pass through the outer membrane, and they are responsible d • Imipenem (with cilastatin as Primaxin) for the entry of several types of antibiotics. Acquired altera- tions in porin structure can lead to microbial resistance to Other Bacterial Cell Wall antibiotics, as is the case with resistance to imipenem. Synthesis Inhibitors The bacterial cytoplasmic membrane is the target of two • Bacitracin peptide antibiotics, daptomycin and polymyxin. These • Fosfomycin (Monurol) drugs act directly on the cell membranes to increase mem- • Vancomycin brane permeability and thereby cause the cytoplasmic con- • Telavancin (Vibativ) tents to leak out of the cell. The properties and uses of these aAlso clavulanate with ticarcillin (Timentin), sulbactam with ampicillin antibiotics are discussed in Chapter 40. A, The gram-positive bacterium has a thick cell wall but does not have an outer membrane. It also has an outer membrane that contains lipopolysaccharide and protein channels called porins. Each disaccharide is attached to others and thereby inhibit the catalytic activity of these enzymes. During this reaction, the terminal This partly accounts for the variation in the sensitivity of d-alanine is removed. The cell wall maintains the shape of the bacterium and protects it from osmotic lysis if it is placed in a hypotonic Other Drugs medium. Bacitracin and fosfomycin inhibit cell wall peptidoglycan This is why inhibition of cell wall synthesis by antimicrobial synthesis by blocking specifc steps in the formation of drugs is usually bactericidal.

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If these cardiovascular effects are too intense discount septra 480 mg on line, they can be managed in several ways order 480mg septra with amex, including (1) decreasing or stopping the infusion discount septra 480mg mastercard, (2) infusing fluid discount septra 480mg free shipping, and (3) elevating the lower extremities. Drug Interactions Dexmedetomidine can enhance the actions of anesthetics, sedatives, hypnotics, and opioids. Preparations, Dosage, and Administration Dexmedetomidine [Precedex] is supplied in solution (100 mcg/mL), which must be diluted to 4 mcg/mL before use. For intensive care sedation, treatment consists of a loading dose (1 mcg/kg infused over 10 minutes) followed by a maintenance infusion of 0. For procedural sedation, treatment typically consists of a loading dose (1 mcg/kg infused over 10 minutes) followed by a maintenance infusion of 0. Epidural Anesthesia Epidural anesthesia is achieved by injecting a local anesthetic into the epidural space (i. A catheter placed in the epidural space allows administration by bolus or by continuous infusion. After administration, diffusion of anesthetic across the dura into the subarachnoid space blocks conduction in nerve roots and in the spinal cord. Diffusion through intervertebral foramina blocks nerves located in the paravertebral region. With epidural administration, anesthetic can reach the systemic circulation in significant amounts. As a result, when the technique is used during delivery, neonatal depression may result. Spinal (Subarachnoid) Anesthesia Technique Spinal anesthesia is produced by injecting local anesthetic into the subarachnoid space. Spread of anesthetic within the subarachnoid space determines the level of anesthesia achieved. Movement of anesthetic within the subarachnoid space is determined by two factors: (1) the density of the anesthetic solution and (2) the position of the patient. Adverse Effects The most significant adverse effect of spinal anesthesia is hypotension. Blood pressure is reduced by venous dilation secondary to blockade of sympathetic nerves. Autonomic blockade may disrupt function of the intestinal and urinary tracts, causing fecal incontinence and either urinary incontinence or urinary retention. The prescriber should be notified if the patient fails to void within 8 hours of the end of surgery. These “spinal” headaches are posture dependent and can be relieved by having the patient assume a supine position. Dosing may consist of an initial weight-based bolus followed by a weight-based infusion titrated to laboratory results. Whether or not a bolus is indicated depends on the indication for treatment and the facility policy. Low-Dose Unfractionated Heparin Therapy Heparin in low doses is given for prophylaxis against thromboembolism in hospitalized patients. Doses of 5000 units are given subcutaneously every 8 to 12 hours depending on patient weight. Protamine Sulfate for Heparin Overdose Protamine sulfate is an antidote to severe heparin overdose. These groups bond ionically with the negative groups on heparin, thereby forming a heparin-protamine complex that is devoid of anticoagulant activity. Neutralization of heparin occurs immediately and lasts for 2 hours, after which additional protamine may be needed. Dosage is based on the fact that 1 mg of protamine will inactivate 100 units of heparin. Hence, for each 100 units of heparin in the body, 1 mg of protamine should be injected. The drug is a synthetic drug chemically related to hirudin, an anticoagulant isolated from the saliva of leeches. Bivalirudin is given in combination with aspirin, clopidogrel, or prasugrel to prevent clot formation in patients undergoing coronary angioplasty. In one trial—the Hirulog Angioplasty Study—bivalirudin plus aspirin was compared with heparin plus aspirin. In a subgroup of patients— those with postinfarction angina—bivalirudin was significantly more effective than heparin. Adverse Effects The most common side effects are back pain, nausea, hypotension, and headache. Other relatively common effects (incidence greater than 5%) include vomiting, abdominal pain, pelvic pain, anxiety, nervousness, insomnia, bradycardia, and fever. However, compared with heparin, bivalirudin causes fewer incidents of major bleeding (3. Coadministration of bivalirudin with heparin, warfarin, or thrombolytic drugs increases the risk for bleeding. Bivalirudin is eliminated primarily by renal excretion and partly by proteolytic cleavage. The half-life is short (25 minutes) in patients with normal renal function but may be longer in patients with renal impairment. However, the drug has one disadvantage: bivalirudin is more expensive than heparin. One single-use vial, good for a full course of treatment, costs about $1000, compared with $10 for an equivalent course of heparin. However, the manufacturer estimates that reductions in bleeding and ischemic complications would save, on average, $1000 per patient, which would offset the greater cost of bivalirudin. Bivalirudin works as well as heparin, is safer, and may be equally cost effective—and hence is considered an attractive alternative to heparin for use during angioplasty. If necessary, bivalirudin may be infused for up to 20 additional hours at a rate of 0. In clinical trials, argatroban reduced development of new thrombosis and permitted restoration of platelet counts. Allergic reactions (dyspnea, cough, rash), which develop in 10% of patients, occur almost exclusively in those receiving either thrombolytic drugs (e. Argatroban has a short half-life (about 45 minutes), owing to rapid metabolism by the liver. Nonetheless, the actions of both products are the same: suppression of coagulation mediated by thrombin and factor Xa. In fact, to protect against thromboembolism, these people typically require lifelong therapy with an anticoagulant, usually warfarin. Treatment consists of a 15-minute loading infusion followed immediately by a continuous maintenance infusion. The loading infusion should begin before delivery or 24 hours before surgery and should continue until normal maintenance coagulation can be reestablished. All three are administered intravenously, usually in combination with aspirin and low-dose heparin. As a result, these drugs can prevent aggregation stimulated by all factors, including collagen, thromboxane A adenosine diphosphate, thrombin, and platelet activation factor. In both cases, symptoms result from thrombosis triggered by disruption of atherosclerotic plaque. However, it does not increase the risk for fatal hemorrhage or hemorrhagic stroke. In the event of severe bleeding, infusion of abciximab and heparin should be discontinued. The drug—neither an antibody nor a peptide—was modeled after a platelet inhibitor isolated from the venom of the saw-scaled viper, a snake indigenous to Africa. Thrombolytic (Fibrinolytic) Drugs As their name implies, thrombolytic drugs are given to remove thrombi that have already formed. This contrasts with the anticoagulants, which are given to prevent thrombus formation.

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The treatment for syphilis cheap 480mg septra overnight delivery, that is less than 1-year duration order 480mg septra overnight delivery, is one injection of long-acting penicillin purchase septra 480 mg visa. If this patient were older purchase 480mg septra otc, for inst ance, in her post menopausal years, squamous cell carcinoma of the vulva would be considered. Systemic diseases such as Behcet’s disease, Candida infec- tion, or vulvar neoplasms should also be considered. Step 4: If negative, then reassess based on the wide differential diagnosis; biopsy may be helpful. T his organism is highly cont agiou s, an d it is t h ou gh t that 20% of wom en in t h eir ch ild bear in g year s are infected. The primary episode is usually a syst emic as well as local disease, wit h t he woman oft en complaining of fever or general malaise. Local infect ion t ypically induces paresthesias before vesicles erupt on a red base. After the primary episode, the recurrent disease is local, with less severe symptoms. The gold standard diagnostic test is viral culture, but polymerase ch ain r eact ion t est s are in cr easin gly u sed becau se they are m or e sen sit ive. Infec- tions occur rarely in the United States and tend to be concentrated in southern regions. The organism is extremely tightly wound, and too thin to be seen on light microscopy. T h e u lcer u sually ar ises 3 weeks aft er exposure and disappears spont aneously aft er 2 t o 6 weeks wit hout t herapy. Darkfield m icr oscopy is an accept ed diagn ost ic t ool, but is limited in availability. Secondary syphilis is usually syst emic, occurring about 9 weeks after the primary chancre. The classic macular papular rash may occur any- wh ere on the body, but usually on the palms and soles of the feet. Flat moist lesions called con dylomat alat a m ay be seen on the vu lva ( Figu r e 39– 1), an d h ave a h igh con cen t r at ion of spir och et es. T r ep on em al an d n on t r ep on em al ser ologic t est s are positive at this stage. Because nontreponemal tests can be falsely positive, a positive treponemal test is required to make a serologic diagnosis. Latency of var yin g d u r at ion occu r s aft er secon d ar y d isease; lat en cy is su b d ivid ed int o early latent (< 1 year in duration), or late latent (> 1 year). If untreated, about one-third of women may progress to tertiary syphilis, which may affect the cardio- vascu lar syst em o r cen t r al n er vo u s syst em. O p t ic at r o p h y, t ab es d o r salis, an d ao r t ic aneurysms are some of t he manifest at ions. Pat ient s wit h lat e-lat ent syph ilis (> 1 year) sh ould be treated with a tot al of 7. In pregnancy, penicillin is t he only known effect ive t reat ment t o prevent or t reat congenit al syph ilis. T h e effect iveness of alt ernat ives t o penicillin in the t reat ment of early and lat ent syph i- lis h as not been well document ed. Treat ment of nonpregnant pen icillin-allergic women wit h doxycycline or t et racycline may be considered. After t herapy, clinical and serologic assessment should be performed at 6 and 12 months after treatment for early syphilis and additionally at 24 months after treating late latent or syphilis of unknown duration. An appropriate response is a four-fold fall in t it ers in 6 t o 12 mont h s, 12 t o 24 mont h s for lat e-lat ent syph ilis. When the titer does not fall appropriately, one possible etiology is neurosyphilis, wh ich may be diagnosed by lumbar punct ure. The organism is now called Klebsiellagran- ulomatis, a Gram-negative pleomorphic bacillus. Large painless ulcerative lesions of the mucus membranes is the typical present ation, usually without lymphade- nopathy. Penicillin G is the recommended treatment for all stages of syphilis in nonpregnant women. The pat ient st ates that she is allergic t o penicillin, wit h hives and swelling of t he t ongue and t hroat in t he past. On examination, she is noted to have atender fluctuant mass which appears above and below the right inguinal ligament. Penicillin G is the recommended treatment for all stages of syphilis and dat a regarding effect iveness of alternat ives to t reat ment for penicillin- allergic pat ient s are limited. It is ver y t h in an d t igh t ly wo u n d an d t h er efo r e n o t visib le o n ligh t m icr o s co p y. Transplacental infection during pregnancy is an important cause of congenit al syphilis. W h en a pr egn ant woman wit h syph ilis is allergic t o penicillin, sh e sh ould undergo desensit iza- tion and receive penicillin. Penicillin is the only known effective treatment for prevent ing congen it al syph ilis. D oxycyclin e u se may lead t o discolorat ion of the child’s teeth, and erythromycin has not been shown to be an effective treatment in treating an infected fetus. T h e classic examinat ion of neurosyphilis is unsteady balance and Argyll Robertson pupils. The primary stage is a painless lesion (papule) which usually only appears for a few days, followed by unilateral painful inguinal adenopa- thy (secondary stage) usually occurring 30 to 60 days after infection. Becau se they gr ow ceph a- lad an d caudad t o the inguinal ligament, t h ere is the so called “groove sign” in wh ich t he inguinal ligament forms a groove in the lymphat ic mass. H erpes is treated with acyclovir; gonorrhea is treated with ceftriaxone; and granuloma inguinale is treated with doxycycline or trimethroprim/ sulfa. Vulvovaginitis, sexually transmitted infections, and pelvic inflammatory disease sepsis. Sh e d e n ie s the u se o f m e d ica t io n s a n d h a s n o sig n ifica n t p a st m e d ica l history. Co n s i d e r a t i o n s This 29-year-old woman has a 2-day history of urinary urgency, frequency, and dysuria, all of which are very typical symptoms of a lower urinary tract infec- tion. Because she does not have fever or flank tenderness, she most likely has a bladder infect ion or simple cyst it is. O t her sympt oms of cyst it is may include hesitancy or hematuria (hemorrhagic cystitis). Urinalysis and/ or urine culture and sensit ivit y (if ant imicrobial resist ance/ complicated infect ion is suspected) would be the most appropriat e t est t o confirm the diagnosis. Current evidence suggests a 3-day course of trimethoprim/ sulfa (Bactrim) as the best agent for uncomplicated cystitis, un less bact er iology pat t er n s in the communit y point t o resist ance; in t hat case, a quinolone such as ciprofloxa- cin t wice daily for 3 days is effect ive. If the ur in e cu lt ur e demon st rat es n o growt h of organisms and the patient still has symptoms, urethritis is a possibility (often cau sed by Chlamydia trachomatis). Finally, some women wit h symptoms of bladder discomfort wit h persistently negat ive urine and uret hral culture may have a chronic condit ion of uret hral syndrome. The most commonly stated reason for the increased incidence of U T Is in women is the shorter length of the female urethra and its increased proximity to the rectum. The most common symptoms of lower tract infection (cystitis) are dysuria, urgency, and urinary frequency. Occasionally, the infection may induce a hem- orrhagic cystitis and the patient will have gross hematuria. Fever is u n com mon u n less there is upper urinary tract/ kidney involvement, which is usually reflected by flank t enderness. The diagnosis of cyst it is hinges on ident ificat ion of pat hogenic bacteria in the urine; bacteriuria is defined as > 100 000 colony-forming units per milliliter of a single uropathogen obtained from a midstream-voided clean catch urine culture. In symptomatic patients, as few as 1000 colony-forming units per millilit er may be significant.

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