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Trimethoprim-sulfamethoxazole Ceftriaxone Ceftazidime

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1 Trimethoprim-sulfamethoxazole Ceftriaxone Ceftazidime
A 30-year-old woman presents with the acute onset of fever, pleuritic chest pain, and a productive cough. The patient's history is unremarkable except for recurrent cystitis for which she takes trimethoprim-sulfamethoxazole. She smokes cigarettes. On physical examination her temperature is 40 °C, pulse rate is 120/min, respiration rate is 36/min, and blood pressure is 130/80 mm Hg. Abnormalities are localized to the right lung where crackles, rhonchi, and egophony are heard. Oxygen saturation is 85% by pulse oximetry. Chest radiograph shows a right lower lobe pneumonia. Sputum Gram stain is purulent with few epithelial cells and a predominance of gram-positive diplococci. Which of the following antimicrobial agents would be the best initial therapy for this patient? Ciprofloxacin Vancomycin Trimethoprim-sulfamethoxazole Ceftriaxone Ceftazidime The patient has a classic presentation and sputum Gram stain for pneumococcal pneumonia. Patients with respiration rates greater than or equal to 30/min have an increased mortality and should be hospitalized. Ceftriaxone and cefotaxime are active against most Streptococcus pneumoniae isolates. The prevalence of penicillin- and multidrug-resistant pneumococci is increasing. Ciprofloxacin has FDA-approved indications for pneumococcal pneumonia but is not the first choice for the patient with pneumococcal pneumonia, because the minimal inhibitory concentrations for many pneumococcal pneumonia infections are close to the maximum serum concentrations of ciprofloxacin. Vancomycin is active against pneumococci, including multidrug-resistant isolates. Recommendations from the Centers for Disease Control and Prevention suggest restricting vancomycin use for patients in whom alternative therapy is not available to prevent further development of vancomycin-resistant organisms. The effectiveness of trimethoprim-sulfamethoxazole against pneumococci is decreasing. This patient takes trimethoprim-sulfamethoxazole for prophylaxis and may be more likely to have colonization with resistant S. pneumoniae. Ceftazidime and ceftizoxime have poor in vitro activity against many isolates (up to 25%) of S. pneumoniae.

2 Infectious Disease review Questions
Hail M. Al-Abdely, MD

3 Which of the following antibiotic regimens should be started promptly?
A 68-year-old man is brought to the emergency department by his wife because of increased cough and confusion. The patient's usual cough had increased over the past 3 days and is associated with increased sputum production and dyspnea. He has an 80-pack-year smoking history. His wife noted confusion for the first time this morning. On physical examination, the patient is somnolent. His neck does not move easily to passive flexion. Neurologic examination is nonfocal. A sputum sample cannot be obtained. Chest radiograph shows a lobar infiltrate. Lumbar puncture with cerebrospinal fluid examination reveals polymorphonuclear pleocytosis with a low glucose, elevated protein, and negative Gram stain. Blood cultures have been drawn. Which of the following antibiotic regimens should be started promptly? Ceftriaxone Ceftriaxone and vancomycin Vancomycin Trimethoprim-sulfamethoxazole Levofloxacin Ceftriaxone alone is active against the principal causes of community-acquired meningitis in adults (pneumococci, meningococci, and, much less often, Haemophilus influenzae). However, the occurrence of resistance to penicillin and occasional cross-resistance to ceftriaxone in approximately 30% of pneumococci dictates that vancomycin be added to the regimen until culture and susceptibility data are known. Vancomycin alone is inadequate because of its less reliable penetration of cerebrospinal fluid than ceftriaxone and its lack of activity against H. influenzae. Trimethoprim-sulfamethoxazole is not appropriate because of cross-resistance in many strains of penicillin-resistant pneumococci. Levofloxacin is not appropriate because data are not available to indicate efficacy for treating pneumococcal meningitis. In patients who have immunosuppressing conditions and meningitis, Listeria monocytogenes should also be covered either with ampicillin (with or without gentamicin) or, in patients who are allergic to penicillins, with trimethoprim-sulfamethoxazole. L. monocytogenes is an unlikely cause of pneumonia, however, and thus would not be a likely consideration in the patient presented.

4 Which of the following is the most appropriate next step?
A 60-year-old woman comes to the emergency department because of a very painful right thigh. She has arthritis and is taking nonsteroidal anti-inflammatory agents for control of joint pain. She also has type 2 diabetes mellitus treated with a sulfonylurea. On Friday morning, she noted pain in her right upper thigh and thought that it might be an exacerbation of her arthritis, so she took an extra dose of ibuprofen. Late that night, the thigh became swollen and exquisitely tender. She went to the emergency department where she is seen by a resident. On physical examination, she is obese and in slight distress. Her temperature is 38.9 °C. Mild tachycardia is noted. The joint examination shows a pattern consistent with osteoarthritis. Her right thigh is swollen and extremely tender to deep touch. There is a small (4 x 5 cm) red patch in the middle of the tender area. A radiograph of the thigh shows no gas in the soft tissues and no bony changes aside from features of osteoarthritis in the hip and knee. She is given cefazolin, 1 g every 8 hours, and is admitted to the hospital with a diagnosis of cellulitis. The next day, her pain is worse, and the red area on her thigh is slightly larger (5 x 5.5 cm). Fever is still present, and she looks more ill. A CT scan of the thigh is performed without intravenous contrast and shows no gas in the soft tissues and diffuse swelling of the muscle groups. Cefazolin is continued at the same dose. On the third day, she is somewhat delirious and requires intravenous morphine for pain control. Which of the following is the most appropriate next step? Epidural placement of a catheter for better pain control Change the cefazolin to vancomycin Add levofloxacin to the cefazolin Elevate the leg and apply warm packs Refer for surgical evaluation This patient was believed to have cellulitis based on local skin findings and fever. However, her initial presentation was suspicious for deeper infection because of pain disproportionate to the area of redness in a patient with diabetes. The subsequent course also suggested more significant infection with worsening pain despite little progression of erythema. The altered mental status is also suggestive of more severe infection. This patient had a MRI scan showing an abscess in the thigh, and surgical exploration showed myonecrosis with Streptococcus pyogenes seen on Gram stain and grown in culture. It is urgently important to recognize deep soft-tissue infection, since progression tends to occur more extensively than external features suggest and surgical débridement is essential for control and cure. Some patients have features of gram-positive toxin syndromes, such as toxic shock syndrome or scarlet fever. Rarely, patients may develop glomerulonephritis or other poststreptococcal diseases following S. pyogenes deep-tissue infection. This patient may have been developing streptococcal toxic shock syndrome at the time surgery was performed. Changing the antibiotic to vancomycin would be appropriate for suspected methicillin-resistant Staphylococcus aureus or enterococcal infection, but this scenario does not suggest uncontrolled skin infection. Similarly, adding levofloxacin would be useful if gram-negative bacteria were involved, but these organisms are relatively infrequent causes of skin or skin structure infections or of myositis. Physical measures such as leg elevation and warm packs may help to reduce symptoms, but they do not alter the course of worsening disease. Pain control is important, but rarely requires epidural narcotics once the infection is properly managed.

5 A 65-year-old woman is seen in a clinic because of cough, shortness of breath, and fever. She has mild Alzheimer's disease and type 2 diabetes mellitus controlled with oral hypoglycemic agents. On physical examination, her temperature is 37.8 °C, pulse rate is 85/min, respiration rate is 24/min, and blood pressure is 145/75 mm Hg. She denies headache. Her neck is supple. Bibasilar crackles and decreased breath sounds are auscultated at the right lung base. Cardiac examination shows an S4 gallop rhythm but no murmur. The abdominal examination is unremarkable. There is mild edema of both ankles. Chest radiograph shows an infiltrate in the right lower lobe without a pleural effusion. The patient is unable to produce sputum for examination. Leukocyte count is 16,000/µL with 93% polymorphonuclear neutrophils, 5% band forms, and 2% lymphocytes. Results of blood cultures are pending. Which of the following is the most appropriate therapy for this patient? Oral trimethoprim-sulfamethoxazole Oral azithromycin Oral levofloxacin Oral cefuroxime axetil Intravenous vancomycin Predictive criteria suggest that this patient with community-acquired pneumonia can be safely managed out of the hospital, so that oral medications should be chosen preferentially. The principal pathogens causing community-acquired pneumonia are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and atypical pathogens such as Legionella spp. A nursing-home patient also has an increased risk of gram-negative pathogens, such as Klebsiella pneumoniae. All of these potential pathogens are likely to be covered by levofloxacin, which is well absorbed orally. Trimethoprim-sulfamethoxazole and cefuroxime axetil would cover H. influenzae and M. catarrhalis, but would not have activity against atypical pathogens. In addition, 20% of strains of S. pneumoniae in the United States are resistant to trimethoprim-sulfamethoxazole and to cefuroxime. Azithromycin provides good coverage for atypical pathogens, H. influenzae, and M. catarrhalis. Its coverage for S. pneumoniae may be adequate in an outpatient, although as many as 50% of penicillin-resistant strains of S. pneumoniae are also resistant to macrolides such as azithromycin. Azithromycin and vancomycin would not cover gram-negative bacteria such as K. pneumoniae in this nursing-home patient.

6 Recurrent central venous catheter sepsis
A 67-year-old man develops a fever while in the intensive care unit following partial colectomy for removal and drainage of a peridiverticular abscess. CT scan of the abdomen shows an intraabdominal abscess, which is drained by placing a percutaneous catheter. Catheter drainage and blood cultures are positive for Enterobacter cloacae. Intravenous catheters are changed, and ceftriaxone and metronidazole are begun. The patient becomes afebrile, and a follow-up blood culture is negative. Four days later, fever recurs, and a blood culture is again positive for E. cloacae. A repeat abdominal CT scan is unchanged. Which of the following is the most likely explanation for the recurrent findings? Recurrent central venous catheter sepsis Resistance of the initial strain of E. cloacae to ceftriaxone Emergence of a mutant, ceftriaxone-resistant strain of E. cloacae Development of endocarditis Resistance of E. cloacae to third-generation cephalosporins such as ceftriaxone may occur in 15% to 30% patients with Enterobacter infections treated with these agents. This resistance is due to selection of chromosomal mutations that cause constitutive increased expression of the chromosomally encoded beta-lactamase, which is present but expressed in small amounts in all susceptible strains of E. cloacae. Resistance occurs when there is a sufficiently large initial population of bacteria (such as in a large abscess) for such mutants to exist and then to persist under the selective pressure of ceftriaxone use. Since the patient responded initially to the use of ceftriaxone, it is unlikely that the initial infecting strain was resistant. Since the central venous catheter was changed at the time of the initial bacteremia, it is unlikely that the new catheter represents the source of the recurrent bacteremia. E. cloacae is an exceedingly rare cause of endocarditis on native heart valves.

7 A 78-year-old woman presents to the emergency department with sudden onset of increasing abdominal pain and fever. On physical examination, her temperature is 39.4 °C, respiration rate is 24/min, and blood pressure is 110/55. Her abdomen is distended and tender, and bowel sounds are decreased. Laboratory studies: Leukocyte count 21,000/µL  Polymorphonuclear neutrophils74%  Band forms10%  Lymphocytes10%  Monocytes 6% Serum total bilirubin 40 mol/dL Serum Alk phos 250 U/L AST35 U/L After intravenous fluids and imipenem-cilastatin are begun, fever resolves and blood pressure normalizes. On the eighth hospital day, diarrhea and abdominal pain develop. An assay for Clostridium difficile toxin is positive, and oral vancomycin is added to imipenem-cilastatin. On the 14th hospital day, fever recurs and blood cultures are obtained. The microbiology laboratory reports the next day that the blood cultures are growing gram-positive cocci in short chains that are resistant to vancomycin. The central venous catheter is changed. What is the most likely causative organism? Streptococcus bovis Streptococcus meliri Staphylococcus aureus Coagulase-negative staph. Enterococcus faecium

8 Ampicillin and gentamicin Chloramphenicol Linezolid Levofloxacin
Which of the following is the most appropriate antimicrobial regimen for this patient? Ampicillin and gentamicin Chloramphenicol Linezolid Levofloxacin Ceftriaxone Enterococcus faecium is the most common species of vancomycin-resistant Enterococcus (VRE) encountered in the United States. Prolonged hospitalization and use of vancomycin for treatment of Clostridium difficile colitis are risk factors for acquisition of VRE. Resistance is due to the acquisition of a cassette of genes that alters the vancomycin-binding site of the terminal D-Ala-D-Ala of the pentapeptide side chains of the cell wall to D-Ala-D-Lac to which vancomycin binds poorly. Quinupristin/dalfopristin is active against most strains of E. faecium, but not against Enterococcus faecalis. Quinupristin/dalfopristin appears to be active in patients with VRE infections. E. faecium, but not E. faecalis, is intrinsically resistant to imipenem, use of which can thus amplify selection of E. faecium and would not be appropriate for therapy. Most strains of vancomycin-resistant E. faecium are also resistant to ampicillin and have high-level resistance to gentamicin. Therefore, a combination of these agents, which would be the regimen of choice for serious infections caused by most vancomycin-susceptible enterococci, is only rarely appropriate for VRE. Ceftriaxone, other cephalosporins, and levofloxacin lack activity against both vancomycin-susceptible and vancomycin-resistant enterococci. Most VRE are susceptible to chloramphenicol in vitro. However, questions have been raised about its efficacy in patients with VRE infection and its rare but serious idiosyncratic side effect (aplastic anemia), which make chloramphenicol a less desirable choice. Some strains of VRE are susceptible to doxycycline, which can also be considered a therapeutic option when susceptibility has been established. There have been no trials comparing the efficacy of quinupristin/dalfopristin, doxycycline, and chloramphenicol for treatment of patients with VRE infections. Linezolid is a new agent that also appears active against VRE.

9 Trimethoprim-sulfamethoxazole Ciprofloxacin
A 78-year-old man presents with a 4-day history of fever and cough productive of thick sputum. He has never smoked. Clarithromycin, given for the past 2 days, has been ineffective. A blood culture drawn in the office is reported to be growing gram-positive cocci in pairs. Chest radiograph shows an infiltrate in the right lower lobe. The patient is unable to produce sputum for examination. Which of the following antibiotics, administered intravenously, is the most appropriate initial therapy? Azithromycin Vancomycin Ceftazidime Trimethoprim-sulfamethoxazole Ciprofloxacin This patient with bacteremic pneumonia is not improving on therapy with clarithromycin, suggesting a clarithromycin-resistant isolate. Gram-positive cocci in pairs growing from the blood culture suggest pneumococci. Vancomycin remains fully active against pneumococci, including those resistant to penicillin, macrolides, and trimethoprim-sulfamethoxazole. Other fluoroquinolones with increased activity against pneumococci, such as levofloxacin and sparfloxacin, might also be considered for this patient. Clarithromycin and other macrolides, such as erythromycin and azithromycin, bind to the bacterial ribosome and inhibit bacterial protein synthesis. Resistance to macrolides occurs by induction of a methylase enzyme that modifies the ribosome and thereby alters the drug target or by active specific efflux. The first mechanism affects clarithromycin, erythromycin, and azithromycin as well as the nonmacrolide, clindamycin, but the second mechanism affects only the macrolides. Since both resistance mechanisms affect all macrolides in clinical use in the United States, the choice of azithromycin would not be appropriate for a patient not responding to clarithromycin. Since there is epidemiologic linkage between resistance to macrolides and resistance to penicillin and to trimethoprim-sulfamethoxazole, trimethoprim-sulfamethoxazole would not be appropriate for this patient. Ceftazidime, in contrast to ceftriaxone and cefotaxime, has only limited activity against pneumococci and would therefore be a poor choice. Ciprofloxacin also has limited activity against pneumococci, and development of pneumococcal infections in patients who are receiving ciprofloxacin for other conditions suggests that its efficacy is not optimal.

10 Salmonella typhimurium Plesiomonas shigelloides
A 45-year-old man presents with fever, cough productive of thick sputum, diarrhea, and abdominal cramps of 4 days' duration after returning from Spain. On physical examination, his temperature is 38.9 °C . Lung examination shows occasional scattered wheezes but no crackles. No cardiac murmur is audible. His abdomen is slightly tender with hyperactive bowel sounds but no guarding or rebound. Leukocyte count is 13,000/µL with 90% polymorphonuclear neutrophils and 10% lymphocytes. A test for fecal leukocytes is positive. After cultures of blood and stool are obtained, the patient is started on ciprofloxacin. For which of the following potential diarrheal pathogens in this patient is resistance to ciprofloxacin most likely? Campylobacter jejuni Salmonella typhi Shigella dysenteriae Salmonella typhimurium Plesiomonas shigelloides Acquired resistance has been reported in Campylobacter jejuni isolated from patients treated with fluoroquinolones for Campylobacter diarrhea and has begun to be seen in isolates from animal sources following the use of fluoroquinolones in food animal production. Resistance is particularly high in Spain, other European countries, and Mexico. Therefore, resistant Campylobacter is likely for this patient, who may have acquired his diarrheal pathogen in Spain. To date, resistance to fluoroquinolones in Shigella and Salmonella in the United States and Europe has been relatively low, although outbreaks of multiresistant Salmonella. typhimurium DT104 have been reported. Plesiomonas shigelloides is a rarely identified diarrheal pathogen, and resistance to fluoroquinolones has not been reported. In Europe, and in Spain in particular, the prevalence of resistance in community isolates of Escherichia coli from patients with urinary tract infections is greater than 15%, raising the possibility that some enteropathogenic strains of E. coli causing diarrhea may also be resistant to fluoroquinolones.

11 Change vancomycin to nafcillin Change vancomycin to ceftriaxone
A 29-year-old man who currently uses injection drugs presents with fever and rigors. On physical examination, his temperature is 40 °C. There are hemorrhagic papular lesions on his distal left index finger and right great toe and petechiae in the palpebral conjunctivae. The lungs are clear. Cardiac examination shows a grade 2/6 systolic ejection murmur and a grade 2/4 diastolic murmur at the upper right and lower left sternal border. Abdominal examination is unremarkable, and there are no joint effusions or tenderness. Leukocyte count is 19,000/µL, and serum creatinine is 1.2 mg/dL. Four sets of blood cultures grow gram-positive cocci in clusters, and vancomycin and gentamicin are begun. The next day, the blood isolates are identified as methicillin-susceptible Staphylococcus aureus. You choose to continue gentamicin. Which of the following changes should also be made in the antibiotic regimen? Continue vancomycin Change vancomycin to nafcillin Change vancomycin to ceftriaxone Change vancomycin to ciprofloxacin Add rifampin The Centers for Disease Control and Prevention recommends avoiding the use of vancomycin except in circumstances in which satisfactory alternatives do not exist. One circumstance in which vancomycin could be avoided is treatment of infections due to methicillin-susceptible Staphylococcus aureus, which will respond to treatment with semisynthetic penicillins such as nafcillin. Initial use of vancomycin is appropriate in this patient until the results of susceptibility testing are available, because infection with methicillin-resistant strains of S. aureus may occur more commonly in injection drug users. After susceptibility to methicillin is documented, however, nafcillin or oxacillin is the preferred agent. For patients with S. aureus endocarditis, studies indicate that a combination of nafcillin given for 6 weeks plus gentamicin given for the first 2 weeks may clear bacteremia more rapidly than nafcillin alone given for 6 weeks; however, outcomes were the same at 6 weeks. Although ceftriaxone is effective in treating endocarditis due to viridans streptococci, its activity against S. aureus is inferior to that of nafcillin. Although the regimen of choice for prosthetic valve endocarditis due to coagulase-negative staphylococci is a combination of vancomycin, gentamicin, and rifampin, addition of rifampin to vancomycin plus gentamicin has not been shown to add therapeutic benefit in patients with S. aureus endocarditis on native valves. Although ciprofloxacin has activity against most methicillin-susceptible (but not methicillin-resistant) strains of S. aureus, it has only been studied in patients with right-sided endocarditis, a milder disease than left-sided endocarditis, and only in combination with rifampin. The peripheral embolic lesions suggest that this patient has left-sided endocarditis.

12 Pseudomonas aeruginosa Methicillin-resistant Staphylococcus aureus
A 42-year-old woman presents after having symptoms of upper respiratory tract infection for 4 days that were followed by 2 days of coughing productive of yellowish phlegm, mild pleuritic chest pain, and fevers to 38.9 °C. The medical history includes type 2 diabetes mellitus but no previous pneumonia. The only medication is an oral contraceptive. The patient reports smoking 5 cigarettes a day for 15 years and denies any risk factors for HIV infection. The review of systems shows mild anorexia, but the patient is able to take oral liquids and food and to go about her daily activities. Patient appears mildly ill but in no distress. Her dentition is good. The temperature is 38.5 °C. The pulse rate is 100/min, respiration rate is 24/min with mild splinting, and blood pressure is 110/60 mm Hg. The chest examination shows dullness to percussion, bronchial breath sounds, and coarse crackles at the left base. The findings of the cardiac, abdominal, and extremity examinations are unremarkable. The leukocyte count is 11,300/µL with 20% band forms. Oxygen saturation is 96% while the patient is breathing room air. A chest radiograph shows left lower lobe consolidation with a blunted left costophrenic angle that suggests a small effusion. What pathogens must be kept in mind in designing an antibiotic regimen for this patient? Pseudomonas aeruginosa Methicillin-resistant Staphylococcus aureus Penicillin-resistant Streptococcus pneumoniae Aspergillus fumigatus Anaerobic bacteria In most cases of community-acquired pneumonia, the responsible pathogen is never identified. Thus the recent guidelines promulgated by the American Thoracic Society and the Infectious Disease Society of America have emphasized the need to begin empiric therapy for community-acquired pneumonia as soon as possible and to base it on the patient's age, comorbid illnesses, and severity of illness. This patient has a mild case of community-acquired pneumonia. Because of her age, lack of serious comorbid illness, and cardiovascular and pulmonary stability, application of the Pneumonia Severity Index scoring system would indicate that a score does not even have to be calculated for this patient and that her risk of dying from this episode is less than 1%. Most patients with this presentation can be treated on an outpatient basis with potent oral antibiotics. In young adults, Mycoplasma pneumoniae and Chlamydia pneumoniae are the most likely pathogens. After young adulthood, Streptococcus pneumoniae rises to the top of the list of microbes isolated in cases of community-acquired pneumonia. Penicillin-resistant S. pneumoniae is a problem in many areas of the United States, and the prevalence varies from locality to locality. Antibiotic resistance in this situation is a relative, not absolute, insensitivity to penicillin that can be overcome in cases of intermediate sensitivity by increasing the dose of penicillin administered. Resistance to other first-line agents for community-acquired pneumonia has been seen in tandem with penicillin resistance, particularly resistance to macrolides, trimethoprim-sulfamethoxazole, and first-generation cephalosporins. Mycoplasma and Chlamydia are still potential pathogens in this case, as is Haemophilus influenzae, the last particularly important among cigarette smokers, such as this patient. Pseudomonas aeruginosa organisms often colonize the respiratory tracts of patients with chronic lung disease, such as cystic fibrosis, and patients who have been hospitalized and received multiple courses of antibiotics. Staphylococcus aureus is another potentially deadly pathogen but one present mainly in patients with a particular predisposing circumstance, such as age older than 60, head injury, or nosocomial pneumonia, none of which pertain to this patient. The special category of methicillin-resistant S. aureus is an important consideration in the care of patients who have been or are currently hospitalized, especially if they are receiving multiple courses of broad-spectrum antibiotics. Aspergillus infection is extremely unlikely for this patient. Aspergillus pneumonia is an opportunistic infection that occurs most commonly among patients undergoing high-dose chemotherapy, bone marrow transplantation, or solid organ transplantation. It is occasionally isolated in sputum culture of patients with long-standing structural lung disease, such as cavitary pulmonary lung disease or chronic obstructive pulmonary disease. A patient with a clinical syndrome suggestive of aspiration pneumonia, especially in the setting of poor dentition, might prompt a clinician to consider specific antibiotic therapy focused at anaerobic pathogens in addition to the previously mentioned considerations. In the absence of such a syndrome, definitive coverage of anaerobes is generally unnecessary.

13 Ampicillin:Resistant Cefazolin:Resistant Cefuroxime:Resistant
A 66-year-old man with a history of significant renal failure due to poorly controlled hypertension is admitted to the intensive care unit following a large subarachnoid hemorrhage. He required intubation on arrival and has remained ventilated for 3 weeks. Seven days after admission, he developed a catheter-associated urinary tract infection due to Escherichia coli, which was treated with ceftriaxone for 7 days. Two days ago (4 weeks after admission), he developed a fever to 39.2 °C, and thick, purulent sputum was suctioned from his endotracheal tube. A chest radiograph showed evidence of a new right lower lobe infiltrate. A Gram's stain of an endotracheal tube aspirate showed abundant polymorphonuclear cells and gram-negative rods. Blood samples were obtained for culture, and the patient was started on empiric therapy with ceftriaxone. This morning, the patient is still febrile and requires vasopressors to maintain his blood pressure. You receive a call from the microbiology laboratory to tell you that the patient's blood cultures are positive for gram-negative rods. The microbiologist also informs you that the endotracheal aspirate is growing E. coli with the following sensitivity pattern: Ampicillin:Resistant Cefazolin:Resistant Cefuroxime:Resistant Ceftriaxone:Sensitive Ceftazidime:Resistant Gentamicin:Sensitive Trim-sulfa:Resistant Ciprofloxacin:Resistant Imipenem:Sensitive What should you do next to manage this patient's infection? Continue the ceftriaxone Discontinue the ceftriaxone and start gentamicin Continue the ceftriaxone and add gentamicin Discontinue the ceftriaxone and start imipenem Continue the ceftriaxone and add imipenem This patient has developed a ventilator-associated pneumonia caused by a multidrug- resistant Escherichia coli. The sensitivity pattern indicates that this organism is likely producing an extended-spectrum beta-lactamase (ESBL). ESBLs typically occur in E. coli and Klebsiella. Patients with infections caused by these organisms often have serious underlying disease, have received previous antibiotic therapy, and have had prolonged stays in an intensive care unit. ESBLs confer resistance to first-, second-, and third-generation cephalosporins, although resistance to third-generation cephalosporins may not always be detected by automated sensitivity testing methods. On sensitivity testing, resistance to the third-generation cephalosporins ceftazidime and cefpodoxime is the most sensitive indicator of the presence of ESBLs. Ceftriaxone and cefotaxime may be falsely classified as sensitive by automated methods, and these results should be ignored if the organism is resistant to other third-generation cephalosporins. Cefotaxime should be discontinued in this patient despite the sensitivity results. ESBLs do not confer resistance to carbapenems such as imipenem, and this class of antibiotics is considered the therapy of choice for invasive infections caused by ESBL-producing organisms. The use of an aminoglycoside in a patient with renal failure and pneumonia would not be considered ideal therapy. The combination of cefotaxime with another antibiotic would provide no advantage in this patient and is not recommended.

14 The best explanation for this outcome is: Resistance to levofloxacin
A 63-year-old woman is hospitalized for symptomatic hyperglycemia and acidosis as complications of diabetes. She has no history of loss of consciousness, confusion, or other neurologic process. She has had two similar hospitalizations over the previous 4 years. After admission, she has a good response to insulin and fluid therapy, but on the third day of hospitalization, she develops a fever, and a chest radiograph reveals an infiltrate in the left upper lobe. Her admission chest radiograph, which had been read as normal, was, in retrospect, found to show a small patch of infiltrate in that same area. Culture of an expectorated sputum specimen shows many leukocytes and some gram-positive diplococci among mixed flora interpreted as normal respiratory flora. The patient's physician prescribes levofloxacin for "community-acquired pneumonia." The patient's fever persists, and a sputum culture done before antibiotics were started is found to show a predominance of pneumococci and normal respiratory flora. Another sputum specimen is sent for culture, and this time, there is essentially a pure growth of pneumococci. Both isolates of pneumococcus are tested for susceptibility according to laboratory protocol, and the results show a penicillin minimal inhibitory concentration (MIC) of 0.05 µg/mL, which is interpreted as "highly susceptible." Levofloxacin was continued for community-acquired pneumonia, but the patient did not improve and continued to produce sputum containing leukocytes and pneumococci. Chest radiographs continued to show an infiltrate in the left upper lobe, without evidence of cavitation or pleural disease. Blood and urine cultures were repeatedly negative. The best explanation for this outcome is: Resistance to levofloxacin Superinfection with hospital flora Recurrent pulmonary emboli or infarcts Anaerobic bacterial pneumonia due to aspiration Laboratory error in determining penicillin MIC There are two forms of pneumococcal resistance to fluoroquinolones. The first is associated with intrinsic weakness of some fluoroquinolones (for example, ciprofloxacin) against gram-positive cocci, including pneumococci. The second is a rare pan-resistance to all fluoroquinolones. This resistance is not associated with resistance to penicillin or other commonly used antimicrobial agents. Anaerobic pneumonias related to aspiration are usually found in the dependent lung areas and are more commonly seen in persons with poor dentition and significant neurologic disease, alcoholism, or other reason for poor glottic protection. Although laboratory testing for pneumococcal resistance to penicillin can be challenging, the use of E-tests or other determinations of minimal inhibitory concentration (MIC) circumvents limitations of in vitro testing. Susceptibility to penicillin is frequently the only susceptibility testing done in many microbiology laboratories because it is a good predictor of susceptibility to other beta-lactams. Many laboratories do not test routinely for resistance to fluoroquinolones. A secondary infection is possible, but in a patient who is generally doing well and has negative cultures of the blood and urine, this is unlikely. Pulmonary emboli can occur in hospitalized patients, but it is improbable that there would be a pulmonary lesion present at the time of admission.

15 Identification:Enterococcus faecium
An 80-year-old woman is admitted to the coronary care unit following a large inferior myocardial infarction. She required immediate intubation and ventilatory assistance. One week after her admission, she developed pneumonia, for which she was treated with a 2-week course of imipenem. During this time, she also developed moderate renal failure, which was believed to be due to poor renal perfusion, and an indwelling urinary catheter was inserted to monitor her urine output. Her clinical status gradually improved, and she was extubated 4 weeks after admission. She was transferred to a medical ward 3 days later. Five weeks after admission, the patient developed a fever and rigors, and blood cultures grew methicillin-resistant Staphylococcus aureus, which was believed to have originated from an infected peripheral intravenous catheter site. The catheter was removed, and she was treated with a 2-week course of vancomycin. She continued to improve slowly with daily physical and occupational therapy. Six weeks after admission, a urine specimen was taken from the indwelling catheter as it was being changed and was sent for culture. Forty-eight hours later, the following identification and sensitivity report was issued from the microbiology laboratory: Identification:Enterococcus faecium Ampicillin:Resistant Gentamicin:Resistant Streptomycin:Resistant Teicoplanin:Sensitive Vancomycin:Resistant The patient denies fevers, chills, and dysuria. Her neutrophil count is within normal limits. Your next action should be to: Start ciprofloxacin and doxycycline Remove the catheter and observe the patient Obtain and start teicoplanin Start linezolid Start quinupristin/dalfopristin This question deals with the differentiation between urinary tract colonization and infection with a multidrug-resistant organism, namely vancomycin-resistant enterococci (VRE). The lower urinary tract of most patients with indwelling urinary catheters becomes colonized with enteric bacteria within a few days of catheterization. Colonization, in turn, is the major risk factor for the development of a subsequent urinary tract infection. This patient has no symptoms or signs of a urinary tract infection; thus, the positive urine culture is indicative of colonization. The appropriate preventive treatment in this case is to simply remove the catheter and observe the patient. Should the patient have developed a symptomatic urinary tract infection or more serious invasive infection with VRE, the therapeutic options are limited, and most are still experimental. As this isolate is teicoplanin-sensitive, it would be appropriate to use this drug should the patient develop an invasive infection. This drug is not licensed in North America, however, and therefore would have to be obtained through the Federal government. Both quinupristin/dalfopristin and linezolid have been studied in the setting of VRE bacteremia with varying success. Finally, ciprofloxacin with or without other drugs has been used to treat resistant enterococcal urinary tract infections because it is highly concentrated in the urine. Its use would not be appropriate for an invasive, non—urinary tract infection.

16 An 84-year-old woman with a 10-year history of dementia is transferred from a nursing home to the hospital for evaluation of a new fever. She is being fed through a gastrostomy tube, and she requires both an indwelling bladder catheter and a diaper. She has no known allergies. She has had three prior episodes of fever in the last 6 months. When she had a fever in the nursing home, she was given ciprofloxacin through the gastrostomy tube. On physical examination in the emergency room, the patient has a temperature of 38.8 °C, pulse rate of 84/min, respiration rate of 24/min, and blood pressure of 94/48 mm Hg. She is unresponsive. Her neck is supple, and her lungs are clear. There is an S4 gallop but no significant murmurs. The abdomen is soft and nontender, with no masses or organomegaly. The extremities are warm but not swollen or red. Rectal examination is normal, and the stool is brown and negative for occult blood. The Foley catheter is filled with cloudy urine. In urinalysis and urine culture reports available from 2 days earlier, urinalysis showed trace protein, many leukocytes, rare erythrocytes, and copious bacteria, and urine culture showed Klebsiella pneumoniae. The susceptibility report was limited and indicated that the organism was susceptible to ceftriaxone and resistant to ceftazidime, ciprofloxacin, tobramycin, and tetracycline. Which of the following antimicrobial agents would be most likely to be effective for this woman? Cefotaxime Aztreonam Imipenem Gentamicin Levofloxacin This patient appears to have a multidrug-resistant strain of Klebsiella pneumoniae. These strains have some features in common. Resistance to one fluoroquinolone indicates decreased susceptibility to other drugs in the same class. Generally, ciprofloxacin has good activity against gram-negative rods, and other fluoroquinolones are equally or less potent. With aminoglycosides, there are two major mechanisms for resistance: decreased permeability or enzymatic inactivation. The former usually confers low-level resistance to all drugs in the class; the latter is often drug-specific. However, the aminoglycoside most likely to be active is usually amikacin, because it is least susceptible to the enzymatic modifications that confer resistance to other drugs in the family. With regard to the beta-lactams, in vitro resistance to ceftazidime and susceptibility to cefotaxime indicate the probable presence of an extended-spectrum beta-lactamase. Although the in vitro information might suggest that cefotaxime would be a useful agent, clinical experience shows a disparity between the laboratory tests and outcome due to significant drug inactivation despite apparent sensitivity. Some laboratories will not report susceptibility to cefotaxime in the setting of a known extended-spectrum beta-lactamase just to avoid confusing the clinician. The extended-spectrum beta-lactamase is closely related phylogenetically to common beta-lactamases but confers broad resistance to cephalosporins, monobactams, and penicillins. It is not active against carbapenems and has limited resistance to inactivation by beta-lactamase inhibitors. Therefore, drugs such as imipenem and piperacillin-tazobactam are often effective in vitro and in vivo. A patient with frequent recurrent infections secondary to dementia and chronic medical illness has a high probability of succumbing to an infection. However, the prompt use of effective antimicrobial agents when there is sudden clinical deterioration can be successful in stabilizing some patients.

17 The most likely reason for his persistent symptoms is:
A 31-year-old married man comes to a local health clinic because of a 2-day history of dysuria and urethral discharge. Otherwise, his health has been good. He takes no medications except ranitidine for occasional heartburn. He is allergic to cephalexin, with which he developed a rash 2 years earlier. He is just back from a trip to sout-east Asia where he had several sexual contacts. Physical examination shows a healthy-looking man in no distress. His vital signs are normal, and the only finding is a copious, yellow urethral discharge. Gram's stain of the discharge shows many polymorphonuclear leukocytes and intracellular and extracellular gram-negative diplococci. The patient is given a single dose of ciprofloxacin and a single dose of azithromycin and told to abstain from sexual activity until all symptoms have been gone for at least 48 hours. He returns to the clinic 3 days later with persistent dysuria and discharge. Gram's stain of the urethral discharge again shows numerous leukocytes and gram-negative intracellular and extracellular diplococci. The most likely reason for his persistent symptoms is: Poor ciprofloxacin absorption secondary to H2-receptor antagonist therapy Insufficient dose of azithromycin Neisserial resistance to ciprofloxacin Mixed initial infection Neisserial infection of his wife Resistance of Neisseria gonorrhoeae to a variety of antimicrobial agents has been developing for decades. Although the most potent cephalosporins are still active in vitro and in vivo, penicillins and tetracyclines (the former mainstays of therapy for gonorrhea) have become unreliable. Fluoroquinolones such as ciprofloxacin are usually active against N. gonorrhoeae, but in this case, the patient appeared to have a resistant strain. Although these strains are still relatively rare, their incidence has been increasing worldwide. Usually patients with these resistant strains experience no relief or only transient relief of their symptoms with treatment, whereas patients with susceptible strains have rapid improvement. Abstention from sexual activity has long been advised, but there are no data to document its efficacy. Many patients with symptomatic gonorrhea find sexual activity uncomfortable and usually refrain on their own. Fluoroquinolones are poorly bioavailable when given with antacids or other medicines containing divalent cations such as magnesium, zinc, and calcium, but there is no diminished absorption with H2-receptor antagonists or proton pump inhibitors. Although this man might have responded to azithromycin, it is not considered a first-line or even a second-line drug for gonorrhea, although it is highly active against Chlamydia. He could very well have had a mixed infection, which is present in 10% to 30% of persons with gonorrhea, but he should still have cleared the gram-negative diplococci unless they were resistant to fluoroquinolones.

18 Which of the following is the best therapy for this patient? Imipenem
A 68-year-old diabetic man was recently discharged from the hospital after treatment for congestive heart failure. While in the hospital, he was found to be colonized with methicillin-resistant Staphylococcus aureus (MRSA) and received chlorhexidine baths and intranasal mupirocin. He was also found to have peripheral neuropathy and a chronic, inactive, small ulcer over the head of the right metatarsal. The patient's son calls this morning to tell you that his hather is very confused, feverish, and sweaty and that his right foot is swollen and red. You ask him to bring him to the hospital, and you meet him in the emergency room. On physical examination, the patient's right foot is inflamed and foul-smelling. Laboratory studies: Leukocyte count 13,000/µL Hemoglobin 11.8 g/dL Blood glucose16 mol/dL Gram's stain of a specimen from the foot ulcer Gram-negative bacilli, gram-positive cocci in chains, and gram-positive cocci in clusters Which of the following is the best therapy for this patient? Imipenem Cefazolin and metronidazole Nafcillin, ceftriaxone, and metronidazole Vancomycin, ceftriaxone, and metronidazole Quinupristin/dalfopristin This patient is probably septic from his infected foot. Because he is a known carrier of methicillin-resistant Staphylococcus aureus (MRSA), antimicrobial coverage should include treatment for MRSA. MRSA strains are resistant to beta-lactams, which would include cephalosporins, imipenem, piperacillin, and nafcillin. The major mechanism for this type of resistance is a chromosomally mediated alteration in a penicillin-bending protein (PBP-2). Therefore, use of a beta-lactamase inhibitor such as ampicillin-sulbactam or piperacillin-tazobactam would not be helpful. Appropriate systemic therapy for MRSA would include vancomycin, streptogramins (quinupristin/dalfopristin), or linezolid. Vancomycin is the preferred therapy, but some strains that are not susceptible to vancomycin have been reported. Because the diabetic foot infection is a polymicrobial infection, broad coverage is needed for anaerobes and aerobic gram-negative bacteria. The spectrum of quinupristin/dalfopristin does not include the latter organisms. The previous mupirocin use does not preclude the presence of MRSA. Intranasal mupirocin is highly effective in eradicating nasal MRSA in healthcare workers but is less effective in sick patients, in whom nasal and especially wound colonization can persist.

19 The infection control committee of KFSH&RC is reviewing strategies to reduce the incidence of antibiotic-resistant nosocomial pneumonia and sepsis. In addition to a multidisciplinary effort, which of the following strategies is most likely to accomplish this goal? Combination antibiotic therapy for serious infections Restricted hospital formulary Routine use of broad-spectrum antibiotics Routine consultation with an infectious disease specialist Routine input from infectious disease specialists is associated with less use of broad-spectrum antibiotics, a more rapid shift to oral antibiotics, and, as part of a multidisciplinary effort, reductions in infections caused by antibiotic-resistant bacteria. Combination antimicrobial therapy has been successfully used to control the emergence of antibiotic-resistant Mycobacterium tuberculosis, but there is no convincing evidence that this strategy works for nosocomial pneumonia or sepsis. A restricted hospital formulary is an effective strategy to decrease the incidence of a specific antibiotic-resistant bacterium but is not effective in reducing the overall incidence of antibiotic resistance. The routine use of broad-spectrum antibiotics escalates, rather than diminishes, the emergence of antibiotic-resistant bacteria.

20 A 29-year-old man is admitted to the hospital with community-acquired pneumonia. Blood cultures yield Streptococcus pneumoniae resistant to penicillin (MIC = 4.0 µg/mL). To which of the following antimicrobial agents is the organism most likely to be susceptible? Azithromycin Ceftriaxone Amoxicillin Levofloxacin Trimethoprim-sulfamethoxazole Strains of Streptococcus pneumoniae that are resistant to penicillin are known to have cross-resistance to other antimicrobial agents such as cephalosporins, macrolides (azithromycin, clarithromycin, and erythromycin), tetracyclines, and trimethoprim-sulfamethoxazole. Resistance to penicillin does not confer resistance to fluoroquinolones

21 Change to ceftriaxone; add anaerobic coverage
A 68-year-old paraplegic man is transferred to the hospital from the nursing home because he has fever and mild confusion. His general physical examination is unchanged since his last office visit, except that over the sacrum he has a deep decubitus ulcer that has developed and progressed rapidly. The admitting physician performs local débridement and wound care and prescribes imipenem for possible sepsis. On the third hospital day, the patient is clinically better, and a blood culture from admission and deep-tissue cultures from the débridement both show Klebsiella pneumoniae with the following resistance phenotype: Ampicillin-Resistant Cefazolin-Resistant Ceftriaxone-Susceptible Ceftazidime-Resistant Imipenem-Susceptible Ciprofloxacin-Resistant Tobramycin-Susceptible Which of the following treatment choices is most reasonable at this point? Continue imipenem Change to ceftriaxone; add anaerobic coverage Change to tobramycin; add anaerobic coverage Change to moxifloxacin alone for broader-spectrum fluoroquinolone coverage Stop antibiotics, as dèbridement has removed the source of the infection This pattern of susceptibility and resistance to beta-lactams is typical of an extended-spectrum beta-lactamase. The susceptibility to ceftriaxone (and other third-generation cephalosporins such as cefotaxime) is somewhat illusory, because these drugs often fail in typical clinical settings with a large burden of organisms. While tobramycin would be expected to work clinically when the in vitro tests show activity, it is not quite as good a drug in situations where tissue necrosis is present. In addition, there is some considerable risk of toxicity in a person who requires a full course of treatment (for example, 2 weeks or more). Antibiotic cessation would be reasonable only if the infection were purely local and completely cleaned up. With the severity of the initial presentation and the bacteremia, it is too early to stop antibiotics. Although moxifloxacin is more broad-spectrum than ciprofloxacin, it does not have enhanced coverage for gram-negative rods. Imipenem is almost always active against extended-spectrum beta-lactamase producers as well as intestinal anaerobes and many enterococci.

22 A 7-day course of amoxicillin
A previously healthy 40-year-old mother of two is evaluated because of a 9-day history of malaise, runny nose, scratchy throat, and cough. She has no fever, chest pain, or shortness of breath. Nasal secretions were clear but now are yellowish; cough is usually nonproductive, except in the morning when it produces green sputum. What is the most appropriate management strategy for this patient? A 7-day course of amoxicillin A 7-day course of amoxicillin-clavulanate Symptomatic treatment and reassurance A 10-day course of levofloxicin The patient has a nonspecific upper respiratory infection (URI). The diagnosis of URI should be used to denote an acute infection in which sinus, pharyngeal, and lower airway symptoms, although frequently present, are not prominent. With rare exceptions, the cause of upper respiratory tract infections is viral. When symptoms are severe, particularly when accompanied by muscle aches and fatigue, influenza and parainfluenza infections are the most common causes, whereas rhinoviruses predominate when symptoms are mild. Other agents that are important causes of upper respiratory tract infection syndromes in adults include adenovirus and respiratory syncytial virus. Most cases of uncomplicated URI in adults resolve spontaneously. The duration of illness is typically 1 to 2 weeks, with most patients feeling much better within the first week. Randomized, placebo-controlled trials of antibiotic use for URI show that antibiotic treatment has no effect on illness resolution or work loss. Although clinicians often use purulent sputum or nasal discharge as indicators of bacterial infection or specific diagnoses such as acute sinusitis or acute bronchitis, these signs are also commonly present in uncomplicated URI. In placebo-controlled trials involving patients who have acute nasopharyngitis, no difference in outcome has been found between patients with and without purulent nasal discharge. Other studies have also failed to find a clinical benefit of antibiotic treatment of adults with cough who had purulent sputum. Therefore prescribing any antibiotic is incorrect.

23 What is the most appropriate management strategy for this patient?
A previously healthy 26-year-old medical student is evaluated because of a 7-day history of abundant, thick, yellow nasal secretions and post-nasal drip. He has no fever and only mild sinus tenderness. He mentions that he has had "sinusitis" before and has always needed an antibiotic. He even suggests which antibiotics could be prescribed. What is the most appropriate management strategy for this patient? Decongestants or nasal sprays and reassurance Antibiotics for 10 days Antibiotics for 1 month Antibiotics for 14 days "Sinusitis" refers to inflammation of the mucosa of the paranasal sinuses. Because sinusitis is invariably accompanied by inflammation of the contiguous nasal mucosa, "rhinosinusitis" has become the preferred terminology. Acute rhinosinusitis is defined by symptom duration of less than 4 weeks. Rhinosinusitis is one of the ten most common diagnoses in ambulatory practice, and is the fifth most common diagnosis for which an antibiotic is prescribed. Primary care physicians tend to think of sinusitis as an acute bacterial infection for which they prescribe an antibiotic in 85% to 98% of cases. Sinusitis is, however, frequently caused by viral infection. It will resolve in the majority of patients without antibiotic treatment, even if it is bacterial in origin. Epidemiologic estimates indicate that only 0.2% to 2% of viral upper respiratory infections in adults are complicated by bacterial rhinosinusitis. In a study of the natural history of rhinovirus illness, length of illness ranged from 1 to 33 days. Most patients were well or nearly well in 7 to 10 days, and one fourth of patients were still symptomatic after 14 days. Bacterial rhinosinusitis is not common in patients with symptoms of less than 7 days' duration; hence, duration of symptoms for 7 days or longer is a moderately sensitive but nonspecific predictor of bacterial rhinosinusitis. Other predictors of bacterial sinusitis include purulent nasal discharge along with maxillary tooth or facial pain—especially when unilateral—unilateral sinus tenderness, and worsening of symptoms after initial improvement. Meta-analyses by the Cochrane Collaboration and the Agency for Health Care Research and Quality (AHRQ) conclude that, although antibiotics are statistically more efficacious than placebo in reducing or eliminating symptoms at 10 and 14 days, the effect size (degree of benefit) is relatively small. Moreover, the majority of placebo-treated patients improve without antibiotic therapy. The AHRQ reported that symptoms improved or resolved in 69% of patients by 14 days without any antibiotic treatment at all (CI: 57% to 79%). On the basis of this evidence, the American College of Physicians-American Society of Internal Medicine and the Centers for Disease Control and Prevention recommend only symptomatic treatment and reassurance as the preferred initial management strategy for patients with mild to moderate symptoms. Antibiotic therapy should be reserved for patients meeting the criteria for the clinical diagnosis of acute bacterial rhinosinusitis with severe symptoms regardless of duration of illness. Initial antibiotic treatment should be with narrow-spectrum agents. Antibiotics favored on the basis of clinical trials are amoxicillin, doxycycline, or trimethoprim-sulfamethoxazole.

24 Stable antibiotic susceptibility patterns for bacteria
A community hospital implements a locally derived set of infection management practice guidelines. Adherence to the guidelines by the medical staff will most likely result in which of the following outcomes? Stable antibiotic susceptibility patterns for bacteria No change in overall use of antibiotics Increase in the use of inadequate antimicrobial treatment regimens Increase in adverse drug effects Guideline use has been associated with stable antibiotic susceptibility patterns for both gram-positive and gram-negative bacteria, possibly as the result of promoting antimicrobial heterogeneity. Guideline use has also been associated with a reduction in the overall use of antibiotics and reduction in the use of inadequate antimicrobial treatment regimens, both of which could affect the development of antibiotic resistance. The use of automated guidelines has been associated with a decrease in adverse drug effects and improved antibiotic selection.

25 Which of the following would be the best answer?
A 42-year-old woman is evaluated because of a 2-day history of dysuria. She had one prior urinary tract infection 7 years earlier and responded to a short course of trimethoprim-sulfamethoxazole. After the urine dipstick shows a strongly positive reaction for nitrites, she asks whether she could again take trimethoprim-sulfamethoxazole. Which of the following would be the best answer? No, trimethoprim-sulfamethoxazole is no longer considered a first-line treatment for urinary tract infection Yes, trimethoprim-sulfamethoxazole is still an effective treatment for urinary tract infection even when resistance is measured in vitro Yes, if local resistance patterns to trimethoprim-sulfamethoxazole show only a small probability of resistance No, prior treatment with trimethoprim-sulfamethoxazole makes it unlikely that the organisms causing the infection are susceptible to trimethoprim-sulfamethoxazole Trimethoprim-sulfamethoxazole was, for a number of years, the principal drug for treatment of cystitis in the United States. Its popularity was related to a high level of efficacy and a relatively low potential to select for resistant organisms in the gastrointestinal tract or the genitals. But over time there has been an increase in resistance to trimethoprim-sulfamethoxazole. Because this resistance is regionally variable, it might be fine to use trimethoprim-sulfamethoxazole to treat urinary tract infection in some parts of the country, but as rates of resistance exceed a certain level (for example, 15% to 20%), it might be more prudent to use other agents such as fluoroquinolones. In some cases cystitis caused by organisms resistant to trimethoprim-sulfamethoxazole will respond to trimethoprim-sulfamethoxazole, but the failure rate is estimated to be 50% to 60%.

26 Salmeterol metered-dose inhaler as needed at bedtime
A 30-year-old otherwise healthy man is evaluated because of a 10-day history of cough. The cough was initially productive of small amounts of clear sputum, which has now turned yellowish. He has no fever, chills, or shortness of breath but has difficulty sleeping because of the persistent cough. On physical examination, his vital signs are normal and examination of the lungs reveals no wheezing, crackles, or rhonchi. In addition to symptomatic relief with antitussives, what is the most appropriate treatment strategy for this patient? Salmeterol metered-dose inhaler as needed at bedtime A 2-week course of clarithromycin A 7-day course of amoxicillin A 7-day course of amoxicillin-clavulanate Observation only Acute bronchitis is a clinical diagnosis, usually referring to an acute respiratory tract infection in which cough, with or without phlegm, is a predominant feature and lasts for less than 3 weeks. In the great majority of cases it resolves with symptomatic treatment only. In the healthy, nonelderly adult (as in this case), pneumonia is uncommon in the absence of vital-sign abnormalities or asymmetrical lung sounds, and chest radiography is usually not indicated. Short-acting beta-agonist inhalers have been shown to be helpful for symptomatic relief of cough for some patients, but use of long-acting beta agonists is not indicated. In epidemiologic studies, respiratory viruses, particularly influenza, appear to cause the majority of cases of uncomplicated acute bronchitis. Specific viruses most frequently associated with acute bronchitis include those that produce primarily lower respiratory tract disease (influenza B, influenza A, parainfluenza 3, and respiratory syncytial virus), as well as viruses that more commonly produce upper respiratory tract symptoms (corona virus, adenovirus, and rhinoviruses). Unless bacterial superinfection is present (defined as pneumonia with an infiltrate on chest radiography), antibiotic treatment does not affect the clinical course of viral respiratory infections. There is no evidence that Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis produce acute bronchitis in adults without underlying lung disease. Randomized placebo-controlled trials have failed to support a role for antibiotic treatment of uncomplicated acute bronchitis. Recent guidelines from the American College of Physicians-American Society of Internal Medicine and the Centers for Disease Control and Prevention are clear that antibiotic therapy is inappropriate for acute uncomplicated bronchitis in otherwise healthy adults. These organizations recommend only symptomatic treatment for patients with cough lasting less than 3 weeks, regardless of sputum production or sputum color, and the absence of vital-sign abnormalities. Clinicians caring for patients with uncomplicated acute bronchitis should discuss with them the lack of benefit of antibiotic treatment for uncomplicated acute bronchitis, and stop prescribing for this condition.

27 Anticoagulation for pulmonary embolus Oral amoxicillin-clavulanate
A 56-year-old businessman is planning a trip to east Asia for a period of 3 weeks. He is in generally good health except for chronic bronchitis. His medicines control his illness fairly well, but he asks if he should carry antibiotics with him in case he should develop an exacerbation. He agrees not to take anything with him, but on his return from the trip he calls from the airport sounding very short of breath and coughing. On examination that day, he has a fever of 38.3 °C and loud rhonchi and some wheezes. A chest radiograph shows some patchy lesions that look worse than on his baseline radiograph. His capillary oxygen saturation is the same as his baseline level. In addition to treatment for his airway disease, which of the following is the next step in this patient's management? Anticoagulation for pulmonary embolus Oral amoxicillin-clavulanate Oral azithromycin Oral gatifloxacin Intravenous ceftazidime Problems of resistance among respiratory bacteria are worldwide. In the United States there is a gradual trend for Streptococcus pneumoniae to be more and more resistant to beta-lactams as well as macrolides. Although there might be concern about pulmonary embolus in a person who has recently made a long airplane flight, the clinical picture in this patient is much more compatible with that of pneumonia. Adjunctive treatments for chronic obstructive pulmonary disease or bronchitis are good therapy, but at this stage, it might be necessary to include antibiotics in the mix. Clavulanate adds nothing to the coverage for S. pneumoniae, although it might make a difference for Haemophilus influenzae. Problems with the macrolides are especially severe in east Asia. The majority of strains of S. pneumoniae are resistant to all the currently available macrolides; fluoroquinolones, however, still seem to be effective. Intravenous antibiotics do not seem to be necessary for this patient, but even if they were to be used, it would make sense to prescribe a drug with more potency for S. pneumoniae. Either a fluoroquinolone or a better beta-lactam would be suitable.

28 What would be the next appropriate step in managing this patient?
A 34-year-old man is evaluated because of a 4-day history of sore throat. He is able to swallow but indicates that the pain is significant. He has taken analgesics inconsistently. He has no febrile sensation or cough. On examination, he is afebrile. His pharynx is erythematous, but no plaques are visible, and he has no tender enlarged cervical lymph nodes. He is concerned because he has small children, and they currently have symptoms of upper respiratory infection, including sore throat and fever. What would be the next appropriate step in managing this patient? Get a rapid strep test and if positive start antibiotics Treat symptoms only Send off a throat culture and treat with antibiotics until result comes back Treat him and his children with antibiotics Acute pharyngitis accounts for 1% to 2% of all visits to outpatient departments, physician offices, and emergency departments. A wide range of infectious agents produces acute pharyngitis, of which viruses are the most common. Group A beta-hemolytic streptococcus (GABHS) is the cause in only about 5% to 15% of adult cases. Yet, physicians prescribe antimicrobial agents to a substantial majority of patients with acute pharyngitis in order to avoid potential complications such as rheumatic fever and acute glomerulonephritis or because of perceived patient expectations. It is important, therefore, to be able to select out the patients with the highest probability of having GABHS and avoid antibiotic treatment for all the others. Clinical criteria have been widely used for this purpose. Although use of a clinical screen alone would leave some patients with GABHS untreated and overtreat some others, it would ensure treatment of the majority of patients with GABHS and dramatically decrease excess antibiotic use. The most reliable predictors of GABHS include the presence of tonsillar exudates; tender enlarged anterior cervical lymph nodes; absence of cough; and history of fever. The patient in this case fulfills only one of these criteria. Rapid antigen tests for GABHS, when compared with the "criterion standard" of throat culture, have widely variable reported sensitivity (58% to 96%) and specificity (63% to 100%), depending on the type of test and practice setting in which the trial occurred. These rapid antigen tests can be done at the bedside, and treatment decisions made in real time. Unfortunately, although many physicians currently perform rapid antigen tests, there is evidence that they frequently ignore negative results, and prescribe antimicrobials even when the tests are negative. Antimicrobial treatment of GABHS pharyngitis leads to a decreased risk of already rare complications and a decrease in the duration of some patient symptoms by 1 or 2 days. Symptomatic improvement requires that treatment begin within 48 to 72 hours of symptom onset. For patients who are antimicrobial- or medication-averse, one could reasonably suggest a policy of no antimicrobial treatment for otherwise healthy adults with acute GABHS pharyngitis, with little measurable adverse consequence. An alternative strategy is to limit antimicrobial therapy to the minority of adults with a high likelihood of GABHS pharyngitis, who will probably benefit. The overwhelming majority of adults with acute pharyngitis (like the patient in this case), however, have a self-limited illness, which would do well with supportive care only. Recent guidelines of the American College of Physicians-American Society of Internal Medicine and of the Centers for Disease Control and Prevention recommend only supportive treatment for adults with acute pharyngitis who do not fulfill the clinical criteria for GABHS.

29 A 19 year-old Saudi female with sickle-cell disease presented to the ER with 2 day history of fever, cough and SOB. O/E was febrile 39C, RR 30 and BP 80/50. Has crackles bilaterally and CXR revealed bilateral lower lobe consolidation. WBC with 35% band forms, HgB 39 gm/l. The appropriate antibiotic regimen for this patient is: Penicilin G 3 MU every 4 hours Ceftriaxone 2gm every 24 hours Ceftazidime 2gm every 8 hours and gentamicin 2mg/kg every 12 hours Vancomycin 1gm every 12 hours and Ceftriaxone 2gm every 24 hours Nafcillin 2gm every 4 hours and ciprofloxacin 400mg i.v every 12 hours

30 A 60 year-old Saudi male, heavy smoker for 40 years
A 60 year-old Saudi male, heavy smoker for 40 years. Presented to ER with 4 months history of fever and yellowish sputum. He lost 10 kgs over 2 months. He was treated with antibiotics twice in another hospital over the past month. He had temporary improvement but got worse after stopping the antibiotics. He is otherwise well with no other illnesses. CXR shown.

31 The most likely explanation for his illness is:
Recurrent aspiration Resistant pneumococcal pneumonia Atypical pneumonia Post obstruction bacterial pneumonia Pulmonary tuberculosis

32 The following is true about necrotizing fasciitis: 
Streptococcus pyogenes is the most common cause in diabetic ulcers progressing to fasciitis Bactroides fragilis is the most common cause of post-operative necrotizing fasciitis of the abdominal wall. Staphylococcus aureus is not a common cause of necrotizing fasciitis in non-diabetics. Antibiotic therapy is the mainstay treatment for necrotizing fasciitis Nafcillin is the drug of choice for necrotizing fascitis.

33 A 24 year-old Saudi female with sickle-cell disease presents to ER with a 10-day history of fever and dry cough and 2 days history of severe bone pain and rigors. Temp 39 C and chest examination was unremarkable. CXR revealed a left upper lobe infiltrates with cavitations. CXR 10 days earlier was normal. The patient is on methotrexate weekly and prednisone daily for rheumatoid arthritis. All the followings are possible causes of the chest infiltrates except. Mycobacterium tuberculosis Staphylococcus aureus Pseudomonas aeruginosa Klebsiella pneumoniae Mixed alpha streptococci and anaerobes

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