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By F. Flint. Berry College.

New evidence suggests that vancomycin failure could be related to inadequate dosing (268 cheap alfuzosin 10 mg otc androgen hormone questionnaire,269) order alfuzosin 10mg without a prescription man health tips in hindi, and some authors argue that trough levels of around 15 to 20 mg/L are needed (270) alfuzosin 10 mg without prescription prostate cancer 7 stage, although the success of this strategy requires confirmation in clinical trials order alfuzosin 10 mg line man health pill buy usa. The addition of rifampin, aminoglycosides, or other drugs has achieved little improvement (272). Thus, quinupristin-dalfopristin has generated worse results than vancomycin (268). However, a combined analysis of the results of two randomized trials comparing linezolid with vancomycin for the treatment of nosocomial pneumonia (each in combination with aztreonam for gram-negative coverage) suggests a therapeutic advantage of linezolid (275). Nosocomial Pneumonia in Critical Care 193 Linezolid might be preferred in patients at risk of or with renal insufficiency in whom vancomycin is often associated with a risk of nephrotoxicity and thus underdosed. Further agents presently under investigation include tigecycline, a new glycylcycline antimicrobial derived from tetracyclines. Tigecycline has an extremely broad spectrum of action against gram-positive, gram-negative, and anaerobic pathogens, with the exception of Pseudomonas (277). Still, the need for mechanical ventilation has been associated with lower microbiologic clearance (278), and cancer patients with refractory pneumonia seem to show a relatively low clinical response rate when treated with this drug (51%) (279). Daptomycin cannot be used to treat pneumonia because it gets inactivated by lung surfactant in the respiratory tract. Investigational glycopeptides, such as telavancin and oritavancin, may eventually play a role in the treatment of nosocomial pneumonia, but a definite date cannot be stated at present. Once the susceptibility pattern is known, many physicians prefer combination therapy with a beta-lactam agent plus either an aminoglycoside or an anti-Pseudomonas fluoroquinolone, based on early findings in patients with bloodstream infections (281). This bacterium is intrinsically resistant to many antimicrobial agents, and the agents found to be most active against it are carbapenems, sulbactam, and polymyxins (56,58). In patients with strains resistant to carbapenems, intravenous colistin has been successfully used (59). For example, vancomycin should not be routinely given at a dose of 1 g q12h, but rather the dose should be calculated by weight in mg/kg (a dose that needs adjusting for renal impairment). Retrospective pharmacokinetic modeling has suggested that the failures described for vancomycin could be the result of inadequate dosing. Many physicians aim for a trough vancomycin concentration of at least 15 to 20 mg/L, although, as mentioned in the previous section, the success of this strategy has not been prospectively confirmed. Only one matched cohort study exists in which continuous vancomycin infusion was associated with reduced mortality (287). Some antibiotics penetrate well and achieve high local concentrations in the lungs, while others do not. For example, most beta-lactam antibiotics achieve less than 50% of their serum concentration in the lungs, while fluoroquinolones and linezolid attain equivalent or higher concentrations than blood levels in bronchial secretions. Table 7 shows how to adjust the antibiotic dose in patients with renal impairment. The direct aerosol 194 Bouza and Burillo Table 7 Antibiotic Dose Adjustment in Patients with Renal Impairment Antibiotic CrCl (mL/min) Dose adjustment Amikacin! Levofloxacin >50 500 mg/24 hr 20–49 500 mg/48 hr <20 500 mg  1, then 250 mg/48 hr Linezolid No adjustment Meropenem >50 No adjustment 26–50 Normal dose q12h 10–25 50% normal dose q12h <10 50% normal dose q24h Nosocomial Pneumonia in Critical Care 195 Table 7 Antibiotic Dose Adjustment in Patients with Renal Impairment (Continued) Antibiotic CrCl (mL/min) Dose adjustment Moxifloxacin No adjustment Piperacillin–tazobactam >40 No adjustment 20–40 4. In the past, aminoglycosides and polymyxins were the most common agents used in aerosols. In a prospective randomized trial, the use of intravenous therapy was compared to the same treatment plus aerosolized tobramycin. The results of this trial suggest no better clinical outcome, but bacterial cultures of the lower respiratory tract were more rapidly eradicated (295). Combination Therapy When considering the use of a single antimicrobial agent as opposed to combined therapy, we first need to make the distinction between the use of multiple antimicrobial agents in the initial empirical regimen (to ensure that a highly resistant pathogen is covered by at least one drug) and that of combination therapy continued intentionally after the pathogen is known to be susceptible to both agents. The former use of combination therapy is uniformly recommended, whereas the latter use remains controversial. The benefits commonly attributed to combination therapy include synergy between drugs and the potential reduction of resistance problems. However, the combined regimen has been even found to fail at avoiding the development of resistance during therapy (283). Two meta-analyses have recently explored the value of combination antimicrobial therapy in patients with sepsis (284) and gram-negative bacteremia (289). No benefits of combination therapy were shown, and nephrotoxicity in patients with sepsis or bacteremia increased. A trend toward improved survival has been previously observed with aminoglycoside-including, but not quinolone-including, combinations (8). Combination therapy could, therefore, be beneficial in patients with severe antimicrobial-resistant infections. Whether this benefit is due to a more reliable initial coverage or a synergistic effect is unclear (290). The nephrotoxicity of aminoglycosides, nevertheless, limits the use of these agents. A seven-day treatment course was described as safe, effective, and less likely to promote the growth of resistant organisms in patients who are clinically improving. Most authors agree, nevertheless, that the length of treatment should be tailored to suit each patient (264). Thus, after 48 to 72 hours of defervescence (apyrexia) and resolution of hypoxemia, antibiotic therapy can be withdrawn (56). Examining the Causes of Treatment Failure Treatment failure should be assessed to simultaneously determine both the pulmonary/ extrapulmonary and infectious/non-infectious causes of a failed response. The etiology of treatment failure can be ascribed to three possible causes: (a) inadequate antibiotic treatment, (b) concomitant foci of infection, or (c) a noninfectious origin of disease (292). In 64% of these nonresponders, at least one cause of nonresponse was identified: inappropriate treatment (23%), superinfection (14%), concomitant foci of infection (27%), and noninfectious origin (16%). The remaining nonresponding patients experienced septic shock or multiple organ dysfunction or had acute respiratory distress syndrome. In this type of situation, we would recommend the following: when there is clinical worsening and a positive culture result, antimicrobial treatment should be adjusted and resistance assessed; further respiratory sampling should be undertaken, using invasive techniques; central lines should be checked and removed, if necessary, and surveillance cultures taken (294); urine cultures; echocardiography; and ultrasonographic examination of the abdomen. Guidelines for the management of respiratory infection: why do we need them, how should they be developed, and can they be useful? Ventilator-associated pneumonia after heart surgery: a prospective analysis and the value of surveillance. Variability in antibiotic prescribing patterns and outcomes in patients with clinically suspected ventilator-associated pneumonia. Device-associated nosocomial infection rates in intensive care units of Argentina. Clinical and economic consequences of ventilator- associated pneumonia: a systematic review. Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. The attributable morbidity and mortality of ventilator- associated pneumonia in the critically ill patient. Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay.

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When investigating the fine details of a patient’s hair from the root in the follicle through to the tip it is important to have a broad understanding of the large variety of observations that can be made on cosmetically normal hair buy 10 mg alfuzosin visa prostate cancer 5k harrisburg pa. Hair shafts can be on the head for a considerable time and even perfectly normal generic 10 mg alfuzosin with visa prostate brachytherapy, unadulterated hair will show a remarkable degree of variability generic alfuzosin 10mg mens health week nz. Once changed by various chemical and physical practices buy alfuzosin 10mg lowest price mens health lunch box, new observations will become the expected norm for that hair type and should not be mistaken as markers of pathology. It is also important to be familiar with the appropriate investigative techniques and their value in add- ing to a diagnosis. While these numbers are open to debate, they serve to provide a good conceptual position for understanding a head of hair. It is 20 Gummer important to view the hair as a complex array of fibers with different properties and behavior at different places in the array. If we were to shave a normal head and then measure the proper- ties of the array in time and space as the hair grew back, a number of differences soon become obvious. As hair emerges from the scalp the fibers are held apart by the spatial arrangement of the follicles in the scalp. As the hair grows progressively longer, the fiber tips gain increasing freedom and can interact with more and more fibers. Interestingly, the hair now feels soft to the touch, even though the fundamental bending and frictional properties of the fibers have not changed. Even the terminology for this same set of fibers changes depending on length, from prickly or stiff to soft and tangled. Most changes are so small that it would be difficult to measure differences over 1 or 2 cm. Increased friction, changes in cutical scale structure, and reduced tensile and torsional strength are all evident. When more drastic changes are made within this period, such as perms, coloring, or relaxing, then measurable changes to the fibers can be quite remarkable. Understanding the hair array would be relatively simple if any change to a fiber repre- sented a single event of no further consequence. However, remembering that hair will stay on the head for some time, an intervention such as a perm or color will change the physico-chemi- cal properties of that fiber until either the fiber is lost or the changes have grown beyond the length of the style and the hair is cut. Chemical changes, in particular, and aggressive physical changes, will change the rate at which the fiber weathers. In turn this increases friction and, as a result, the degree of interaction between adjacent fibers. There is, fortunately, a distinct advantage to the hair remaining on the head for so long. It offers an additional historical means of interrogating the patient’s history, either real or perceived. For example “all my hair fell out and it has taken 3 months to grow back” would be in conflict with the presence of mid- to shoulder-length hair. Most people are aware of the unsightly root growth experienced by regular hair coloring (Fig. Rather than being a problem, this growth line provides a unique piece of diagnostic evidence for the last coloring event. Consideration should be given to the patient’s age as habits and practices will vary (Table 1). Permanent hair coloring under the age of 16 is unusual, whereas it dominates in the over-40 female population. Hair bleaching is common between the ages of 18 and 30, with more natural colors used as age increases. Temporary hair straightening for teenagers and women in their twenties has become a fashion essential. In ethnic circles voluminous Afro styles have given way to elegant, chemically straightened hair. In a very visual world where individuals are judged on personal appearance, it is essential for hair to look its very best. To achieve fashion and social acceptance, extreme modification of the hair shaft is often required. Even typical day-to-day cosmetic regimens have a subtle, yet accepted, nega- tive effect on hair. There is little doubt that hair that is clean, conditioned, and manageable reflects positively on the owner. To achieve healthy-looking hair requires the use of surfac- tants that, over time, elute lipids and proteins from the hair. It has long been recognized that regular washing steadily elutes proteinaceous material from the endocuticle, which results in an increase in the number of holes under each cuticle cell toward the tip of the fiber (Fig. Regular grooming causes physical damage to the cuticle and hyper-extension of the cortex. However, routine shampooing and combing form an acceptable balance between small nega- tive changes to the fiber and large visual benefits to both the hairstyle and the owner. Indeed, it is only with the advent of modern shampoo and conditioner formulations that the individual can achieve the desired hair appearance for the days or years that a fiber remains on the head. It is only when the more aggressive physical and chemical processes are conducted on the hair that the rate of damage exceeds both the durability of hair and the replacement of fibers. In truth they can, by matching the cosmetic damage to the rate of growth and not exceeding the parameters. If care is not taken, the end effects are rapid hair breakage, loss of shine, tangling, and occasionally, temporary loss of hair density and length. Permanent Hair Coloring The aim of this section is to look at the changes induced in the hair fiber by coloring processes and not the detailed chemistry of hair coloring. However, a brief overview gives a greater understanding of how and why the fundamental structure of the fiber is affected. Permanent hair colors result in a change to the natural color of hair that, although subject to fading, will only be completely lost when the hair is cut or re-colored. This class of products also includes products designed to lighten, or bleach, the natural color of hair. To change the natural color of hair the following steps must occur: (i) remove or lighten the natural hair color, i. To achieve the color, low pH hydrogen peroxide (developer) is mixed with high pH dyes (tint). The acti- vated or alkaline hydrogen peroxide both bleaches melanin in the cortex and develops the new colors from the tint. In particular, blonde shades are not simply achieved by bleaching melanin and they require the formation of new dye colors to offset red and brass tones left by the incom- plete degradation of melanin. As alkaline hydrogen peroxide diffuses through the fiber it encounters transition metal ions that occur naturally in hair, as well as those acquired from the environment, e. Rapid degradation of peroxide forms the highly damaging and non- specific hydroxyl radical. A fundamental challenge to the colorant formulator is accessing and decolorizing mela- nin that occurs only in the cortex while minimizing damage to the rest of the fiber. First, alkaline peroxide must travel through the cuticle and will cause damage en route. Due to the relatively low concentration of melanin in Caucasian hair there is a greater chance that the peroxide will interact with the hair structure and damage the proteins in the cortex than that it will interact with melanin. As a result, permanent hair colors cause measurable damage to the tensile and torsional properties of the hair fiber. All unmodified cuticle cells are covered in a covalently bound fatty acid on the outer aspect of the cell.

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Single fever spikes of the transient bacteremias are a diagnostic not a therapeutic problem generic 10mg alfuzosin with visa prostate quercetin. Fever secondary to blood products/blood transfusions are a frequent occurrence generic alfuzosin 10mg otc prostate zoloft, and are most commonly manifested by fever following the infusion best 10mg alfuzosin prostate cancer zigns. Most reactions occur within the first 72 hours after the blood/blood product transfusion discount alfuzosin 10mg free shipping mens health 60 day transformation review, and most reactions within the 72-hour period occur in the first 24 to 48 hours. There are very few reactions after 72 hours, but there is a smaller peak five to seven days after the blood transfusion, which although very uncommon, may occur. The temperature elevations associated with late blood transfusion reactions are lower than those with reactions occurring soon after blood transfusion. The fever subsequent to the transient bacteremia results from cytokine release and is not indicative of a prolonged exposure to the infecting agent, but rather represents the post-bacteremia chemokine-induced febrile response. The temperature 8 Cunha elevations from manipulation of a colonized infected mucosal surface persist long after the bacteremia has ceased (1,3–5,24–27). In patients with fever spikes due to transient bacteremias following manipulation of a colonized or infected mucosal surface, or secondary to a blood/blood product transfusion, may be inferred by the temporal relationship of the event and the appearance of the fever. In addition to the temporal relationship between the fever and the transient bacteremia or transfusion-related febrile response is the characteristic of the fever curve, i. The clinician must rely upon associated findings in the history and physical, or among laboratory or radiology tests to narrow down the cause of the fever. Pulse–temperature relationships are also of help in differentiating the causes of fever in patients with multiple temperature spikes over a period of days (1–5,10). Assuming that there is no characteristic fever pattern, the presence or absence of a pulse–temperature deficit is useful. The diagnostic significance of relative bradycardia can only be applied in patients who have normal pulse–temperature relationships, i. Any patient on these medications who develop fever will develop relative bradycardia, thus eliminating the usefulness of this important diagnostic sign in patients with relative bradycardia (Table 6) (1,5,33–35). Fever secondary to acute myocardial infarction, pulmonary embolus, acute pancreatitis, are all associated with fevers of short duration. If present in patients with these underlying diagnoses, a fever >1028F or one that lasts for more than three days should suggest a complication or an alternate diagnosis. Clinicians should try to determine what noninfectious disorder is causing the fever so that undue resources will not be expended looking for an unlikely infectious disease explanation for the fever (1–10,24–30). Prolonged fevers that become high spiking fevers should suggest the possibility of nosocomial endocarditis related to a central line or invasive cardiac procedure. Prolonged high spiking fevers can also be due to septic thrombophlebitis or an undrained abscess. Physicians should always be suspicious of the possibility of drug fever when other diagnostic possibilities have been exhausted. Drug fever may occur in individuals who have just recently been started on the sensitizing medication, or more commonly who have been on a sensitizing medication for a long period of time without previous problems. Patients with drug fever do not necessarily have multiple allergies to medications and are not usually atopic. However, the likelihood of drug fever is enhanced in patients who are atopic with multiple drug allergies. Other conditions aside, patients look “inappropriately well” for the degree of fever, which is different from that of the toxemic patient with a serious bacterial systemic infection. Relative bradycardia is invariably present excluding patients on b-blocker therapy, those with arrhythmias, heart block, or pacemaker-induced rhythms (1,5,41,42). Eosinophils are often present early in the differential count, but less commonly is their actual eosinophilia. The sedimentation rate also is increased after surgical procedures, negating the usefulness of this test in the postoperative fever patient. Often such mild increases in the serum transaminases are overlooked by clinicians as acute-phase reactants or as not being very elevated. However, in a patient with an obscure otherwise unexplained fever, the constellation of nonspecific findings including relative bradycardia, slightly increased serum transaminases, and eosinophils in the differential count is sufficient to make a presumptive diagnosis of drug fever (Tables 7 and 8)(1–5,8,30–35). It is a popular misconception that antibiotics are the most common cause of drug fever. Since patients are usually receiving multiple medications, it is not always possible to discontinue the one agent likely to be the cause of the drug fever. The clinician should discontinue the most likely agent that is not life supporting or essential first, in order to properly interpret the decrease in temperature if indeed that was the sensitizing agent responsible for the drug fever. If the agent that is likely to cause the drug fever cannot be discontinued, every attempt should be made to find an equivalent nonallergic substitute, i. If the agent responsible for the drug fever is discontinued, temperatures will decrease to near normal/normal within 72 hours. If the temperature does not decrease within 72 hours, then the clinician should discontinue sequentially one drug at a time, those that are likely to be the causes of drug fever. If the fever is associated with drug rash, it may take days to weeks to return to normal after the sensitizing drug is discontinued (Tables 7 and 8) (5,27,41–43). Drug rashes usually maculopapular (occasionally with a petechial component), central, and may involve palms/soles. Positive catheter tip culture without bacteremia indicates only a colonized catheter. Changing the catheter over a guidewire does not subject the patient to the possibility of a pneumothorax from a subclavian insertion (8,10,21,32,38,39). Femoral catheters are the ones most likely to be infected followed by internal jugular have been in place for months inserted catheters. Many times catheters are often needlessly changed when patients, particularly postoperative patients spike a fever in the first two to three days postoperatively. Diagnostic Significance of Relative Bradycardia Relative bradycardia combined in a patient with an obscure fever is an extremely useful diagnostic sign. Relative bradycardia, like other signs, should be considered in concert with other clinical findings to prompt further diagnostic testing for specific infectious diseases and to eliminate the noninfectious disorders associated with relative bradycardia from further consideration (Tables 9 and 10) (5,41,42). Diagnostic Fever Curves Fever patterns are often considered nonspecific, therefore, have limited diagnostic specificity. It is true that patients being intermittently given antipyretics and being instrumented in a variety of anatomical locations do have complex fever patterns. A “camel back” pattern should suggest the possibility of Colorado tick fever, dengue, leptospirosis, brucellosis, lymphocytic choriomeningitis, yellow fever, the African hemorrhagic fevers, rat bite fever, and smallpox (5,41–46). A relapsing fever pattern suggests malaria, rat bite fever, chronic meningococcemia, dengue, brucellosis, cholangitis, smallpox, yellow fever, and relapsing fever. Clinical Approach to Fever in Critical Care 13 Table 9 Determination of Relative Bradycardia Criteria: Inclusive l Patient must be an adult, i. These findings should limit diagnostic possibilities and prompt the clinician to order specific diagnostic testing for likely diagnostic possibilities (1,5,44). This is done by analyzing the rapidity of onset of the fever, the height of the fever, the relationship of the fever to the pulse, the fever patterns, and the duration of the fever. Particularly in perplexing cases of fever, the characteristics of fever resolution also have diagnostic significance. The rapidity and completeness of the fever pattern resolution attests to the effective treatment or resolution of the noninfectious or infectious process. Fever defervescence patterns are as predictable as fever patterns and are also useful in predicting complications secondary to the disorder or therapy. Meningococcal meningitis defervesces quickly over one to three days whereas Haemophilus influenzae meningitis resolves over three to five days, and severe pneumococcal meningitis may take a week or longer for the fever to decrease/become afebrile. Viral causes of meningitis or encephalitis defervesce very slowly over a seven-day period, and by monitoring the fever defervescence pattern a clinician can easily differentiate viral meningitis/encephalitis from bacterial meningitis. Because fever defervescence patterns may also point to complications, the astute clinician will monitor the fever pattern post therapy, looking for an unexpected temperature spike after the patient has defervesced. In patients with endocarditis, the fever defervescence pattern is also pathogen related.

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