The first option seems to be the correct one, due to the low probability of P. jirovecii infection in a patient with more than 500 CD4 lymphocytes and undetectable viral load. It is most likely to be a pneumococcal infection that we cover with Ceftriaxone and with azithromycin we cover the so-called "atypical" ones. Meropenem is an antibiotic with too broad a spectrum, which would be an option in in-hospital pneumonia caused by P. aeruginosa, a bacterial agent that can also cause pneumonia in HIV patients, but this is not common.

The first option seems to be [HIDDEN], due to the low probability of P. jirovecii infection in a patient with more than 500 CD4 lymphocytes and undetectable viral load. It is most likely to be a pneumococcal infection that we cover with Ceftriaxone and with azithromycin we cover the so-called "atypical" ones. Meropenem is an antibiotic with too broad a spectrum, which would be [HIDDEN] in in-hospital pneumonia caused by P. aeruginosa, a bacterial agent that can also cause pneumonia in HIV patients, but this is not common.

A 45-year-old man consults for a productive cough, pleuritic pain in the right flank and fever of 48 h of evolution. He has a baseline O2 saturation of 88% and rales in the right base. Chest X-ray shows a right basal consolidation. She has a history of HIV infection well controlled with antiretroviral drugs (CD4 lymphocytes 550 ce/uL and undetectable HIV viral load). Which of the following empirical antimicrobial treatments do you consider most appropriate?

Cefiriaxone 2 g and azithromycin 500 mg every 24 hours.

Cefiriaxone 2 g, azithrornicin 500 mg every 24 h and trimethoprim-sulfamethoxazole 5 mg/kg/8 h (based on trimethoprim doses).

Methyl-prednisolone 40 mg/day, cefiriaxone 2 g IV 124 h and trimethoprim-sulfamethoxazole 5 mg/kg/8 h (based on trimethoprim doses).

Meropenem I g/8 h and vancomycin I g/l2 h.

InternalMed_Harrison

Amoxicillin, 500 mg PO q8h × 60 d, likely to be effective if strain is penicillin sensitive Active disease: Ciprofloxacin, 400 mg IV q12h or doxycycline, 100 mg IV q12h plus Clindamycin, 900 mg IV q8h and/or rifampin, 300 mg IV q12h; switch to PO when stable × 60 d total plus Raxibacumab, 40 mg/kg IV over 2.25 h; diphenhydramine to reduce reaction Gentamicin, 2.0 mg/kg IV loading then 1.7 mg/kg q8h IV or Streptomycin, 1.0 g q12h IM or IV Alternatives include doxycycline, 100 mg bid PO or IV; chloramphenicol, 500 mg qid PO or IV Supportive measures; consideration for cidofovir, tecovirimat, antivaccinia immunoglobulin Streptomycin, 1 g IM bid or Gentamicin, 5 mg/kg per day div q8h IV for 14 days or Doxycycline, 100 mg IV bid or Chloramphenicol, 15 mg/kg up to 1 g IV qid or Ciprofloxacin, 400 mg IV bid Ribavirin 30 mg/kg up to 2 g × 1, followed by 16 mg/kg IV up to 1 g q6h for 4 days, followed by 8 mg/ kg IV up to 0.5 g q8h × 6 days

InternalMed_Harrison

For outpatient management, amoxicillin (1 g every 8 h) provides effective treatment for virtually all cases of pneumococcal pneumonia. Neither cephalosporins nor quinolones, which are far more expensive, offer any advantage over amoxicillin. Levofloxacin (500–750 mg/d as a single dose) and moxifloxacin (400 mg/d as a single dose) also are highly likely to be effective in the United States except in patients who come from closed populations where these drugs are used widely or who have themselves been treated recently with a quinolone. Clindamycin (600–1200 mg/d every 6 h) is effective in 90% of cases and azithromycin (500 mg on day 1 followed by 250–500 mg/d) or clarithromycin (500–750 mg/d as a single dose) in 80% of cases. Treatment failure resulting in bacteremic disease due to macrolide-resistant isolates has been amply documented in patients given azithromycin empirically. As noted above, rates of resistance to all these antibiotics are relatively low in some countries and much

InternalMed_Harrison

7. Volume overexpansion with IV fluid administration is not uncommon and contributes to the development of hyperchloremic acidosis during the later stages of treatment of DKA. Volume overexpansion should be avoided. A 25-year-old man with a 6-year history of HIV-AIDS complicated recently by Pneumocystis jiroveci pneumonia (PCP) was treated with intravenous trimethoprim-sulfamethoxazole (20 mg trimethoprim/kg per day). On day 4 of treatment, the following laboratory data were PART 2 Cardinal Manifestations and Presentation of Diseases H2O AQP-2AQP-3, 4 H2O

InternalMed_Harrison

As a result of the increased prevalence of resistant pneumococci, first-line therapy for persons ≥1 month of age is a combination of vancomycin (adults, 30–60 mg/kg per day; infants and children, 60 mg/kg per day) and cefotaxime (adults, 8–12 g/d in 4–6 divided doses; children, 225–300 mg/kg per day in 1 dose or 2 divided doses) or ceftriaxone (adults, 4 g/d in 1 dose or 2 divided doses; children, 100 mg/kg per day in 1 dose or 2 divided doses). If children are hypersensitive to β-lactam agents (penicillins and cephalosporins), rifampin (adults, 600 mg/d; children, 20 mg/d in 1 dose or 2 divided doses) can be substituted for cefotaxime or ceftriaxone. A repeat lumbar puncture should be considered after 48 h if the organism is not susceptible to penicillin and information on cephalosporin sensitivity is not yet available, if the patient’s clinical condition does not improve or deteriorates, or if dexamethasone has been administered and may be compromising clinical evaluation. When

InternalMed_Harrison

Cefoxitin, 2 g q6h; A combination of metronidazole (500 mg q8–12h) plus cefazolin (1–2 g q8h) or cefuroxime (1.5 g q8h) or ceftriaxone (1–2 g q12–24h) or cefotaxime (1–2 g q6–8h) A carbapenem (imipenem, 1 g q8h; meropenem, 1 g q8h; doripenem, 500 mg q8h); Piperacillin-tazobactam, 3.375 g q6hf; A combination of metronidazole (500 mg q8–12h) plus an antipseudomonal cephalosporin (cefepime, 2 g q8–12h; ceftazidime, 2 g q8h) or an antipseudomonal fluoroquinolone (ciprofloxacin, 400 mg q12h; levofloxacin, 750 mg q24h) — Dexamethasone (0.15 mg/ kg IV q6h for 2–4 d) should be added for patients with suspected or proven pneumococcal meningitis, with the first dose administered 10–20 min before the first dose of antibiotics. If MRSA is a consideration, add vancomycin (15 mg/kg q12hb) or linezolid (600 mg q12h); daptomycin should not be used in patients with pneumonia. If MRSA is a consideration, add vancomycin (15 mg/kg q12hb). 159, 201, and pathogen-specific chapters

Toxic epidermal necrolysis following combination of methotrexate and trimethoprim-sulfamethoxazole.

A 15-year-old boy with T-cell acute lymphoblastic leukemia (ALL) (FAB L1), diagnosed in 1995, received combination chemotherapy consisting of 6 weeks of induction (vincristine, epirubicin, L-asparaginase, prednisolone) and 2 weeks of consolidation (cytosine arabinosides, etoposide). After achieving remission, for further maintenance of remission, he was treated with 14 cycles of intensive chemotherapy consisting of 6-MP, 10 mg/kg orally on the first 4 days, and cyclophosphamide, 1200 mg/m2, vincristine, 1.5 mg/m2, epirubicin, 15 mg/m2, and cytosine arabinoside, 40 mg/m2, intravenously on days 4, 11, 39, and 40, respectively. On day 18 of each cycle, he received intravenous methotrexate (MTX) infusion in a total dose of 150 mg/m2 plus oral leucovorin (30 mg/m2 ) rescue 36 h after starting MTX therapy. In addition, oral trimethoprim-sulfamethoxazole was given regularly to prevent Pneumocystis carinii infection. The patient achieved remission during the first course of treatment, but 8 months later the disease relapsed. He then received four doses of MTX (800 mg intravenously) plus leucovorin rescue in the following 4 months. During the last MTX therapy, small hemorrhagic bullae were found on the lateral side of the right ankle, but subsided after a few days. Due to partial remission of the disease, he was admitted again in January 1999 for high-dose MTX therapy. An initial hemogram on admission revealed hemoglobin 7.2 g/dL, white cell count 15,200/mm3, platelet count 153/mm3, blood creatinine 0.5 mg/dL, and alanine leucine aminotransferase (ALT) 20 U/L. He received 8500 mg of MTX (5000 mg/m2 ) as a continuous intravenous infusion for 24 h. Thirty-six hours after the start of MTX infusion, leucovorin (30 mg, intravenous) rescue was initiated every 6 h for 3 days. Another preventive measure to cover MTX toxicity included aggressive intravenous fluid replacement (4 L/m2 /day) and the addition of 25 meq/L sodium bicarbonate to the intravenous fluid to alkalinize the urine. Concurrent medication included 6-MP (50 mg) once daily and trimethoprim-sulfamethoxazole (120 mg, 600 mg) twice daily every other day. Plasma MTX levels were 52.36 micromol/L 24 h after MTX infusion, 1.87 micromol/L after 48 h, 0.57 micromol/L after 72 h, and 0.41 micromol/L after 96 h. These indicated delayed MTX plasma clearance. The blood creatinine level was mildly elevated from 0.5 mg/dL to 0.7 mg/dL. Thirty-six hours after the administration of MTX, the patient developed an erythematous painful swelling on the right middle finger. The erythema, with subsequent large bulla formation, progressed to all the fingers, toes, palms, and the soles of the feet. Some erythematous to hemorrhagic papules also appeared on the bilateral elbows. Subsequently, diffuse tender erythema with extensive erosions and focal tiny pustules developed on the back, abdomen, proximal extremities, and face (Fig. 1a,b). A positive Nikolsky's sign was also present. A biopsy specimen of the right dorsal hand lesion revealed parakeratosis, detached acanthotic epidermis with scattered necrotic keratinocytes, dyskeratotic cells and nuclear atypia, neutrophilic exocytosis, and many neutrophils in the papillary dermis (Fig. 2). The skin condition deteriorated rapidly. Toxic epidermal necrolysis-like lesions involved 90% of the total body surface on the fifth day after MTX infusion. Mucositis, diarrhea, involuntary tremor, fever, and chills were noted. The patient was then sent to the burn unit for intensive skin care. Ten days after MTX therapy, profound agranulocytosis and thrombocytopenia (white cell count 100/mm3, platelets 14,000/mm3, and hemoglobin 5.6 g/dL) were found. The patient was then started on granulocyte colony stimulation factor (G-CSF, 5 microg/kg/day), but his general condition deteriorated rapidly and he died 6 days later due to septic shock and multiple organ failure.

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12 Alternative treatments for mild to moderate PCP include dapsone/ trimethoprim, clindamycin/primaquine, and atovaquone. IV pentami dine is the treatment of choice for severe disease in the patient unable 8 to tolerate TMP/SMX. For patients with a Pao <70 mmHg or with an 6 a–a gradient >35 mmHg, adjunct glucocorticoid therapy should be used in addition to specific antimicrobials. Overall, treatment should be continued for 21 days and followed by secondary prophylaxis. 2 Prophylaxis for PCP is indicated for any HIV-infected individual who 0 has experienced a prior bout of PCP, any patient with a CD4+ T cell count of <200/μL or a CD4 percentage <15, any patient with unex-

In Vitro Activity and In Vivo Efficacy of Cefiderocol against Stenotrophomonas maltophilia.

Cefiderocol is a novel siderophore cephalosporin antibiotic with broad coverage against difficult-to-treat Gram-negative bacteria, including those resistant to carbapenems. Its activity against <iStenotrophomonas maltophilia</i was investigated <iin vitro</i against clinical isolates and in lung infection models using strains either resistant (SR202006) or susceptible (SR201934, SR200614) to trimethoprim-sulfamethoxazole. Cefiderocol demonstrated potent <iin vitro</i activity against all 217 <iS. maltophilia</i clinical isolates tested (MIC<sub50</sub, 0.063 μg/ml; MIC<sub90</sub, 0.25 μg/ml). Cefiderocol also demonstrated low MICs against the trimethoprim-sulfamethoxazole-resistant <iS. maltophilia</i strains (i.e., SR202006; MIC, 0.125 μg/ml). In a neutropenic mouse lung infection model, cefiderocol (30 mg/kg body weight and 100 mg/kg) demonstrated a significant, dose-dependent reduction in the lung viable bacteria cell count compared with untreated controls in <iS. maltophilia</i infection and was the only antibiotic tested to show a similar significant effect in a trimethoprim-sulfamethoxazole-resistant <iS. maltophilia</i infection. In immunocompetent rat lung infection models of <iS. maltophilia</i, humanized dosing of cefiderocol (2 g every 8 h) and meropenem (1 g every 8 h) revealed pharmacokinetic profiles similar to those in human subjects, and the humanized cefiderocol dosing significantly reduced the lung viable bacteria cell count compared with baseline controls, which received no intervention. Together, the results from these studies suggest that cefiderocol could provide an effective alternative treatment option for <iS. maltophilia</i infections in the lower respiratory tract, particularly strains resistant to empirical antibiotics, such as trimethoprim-sulfamethoxazole or minocycline.

Evaluation of the novel combination of high-dose daptomycin plus trimethoprim-sulfamethoxazole against daptomycin-nonsusceptible methicillin-resistant Staphylococcus aureus using an in vitro pharmacokinetic/pharmacodynamic model of simulated endocardial vegetations.

Daptomycin-nonsusceptible (DNS) Staphylococcus aureus is found in difficult-to-treat infections, and the optimal therapy is unknown. We investigated the activity of high-dose (HD) daptomycin plus trimethoprim-sulfamethoxazole de-escalated to HD daptomycin or trimethoprim-sulfamethoxazole against 4 clinical DNS methicillin-resistant S. aureus (MRSA) isolates in an in vitro pharmacokinetic/pharmacodynamic model of simulated endocardial vegetations (10(9) CFU/g). Simulated regimens included HD daptomycin at 10 mg/kg/day for 14 days, trimethoprim-sulfamethoxazole at 160/800 mg every 12 h for 14 days, HD daptomycin plus trimethoprim-sulfamethoxazole for 14 days, and the combination for 7 days de-escalated to HD daptomycin for 7 days and de-escalated to trimethoprim-sulfamethoxazole for 7 days. Differences in CFU/g (at 168 and 336 h) were evaluated by analysis of variance (ANOVA) with a Tukey's post hoc test. Daptomycin MICs were 4 μg/ml (SA H9749-1, vancomycin-intermediate Staphylococcus aureus; R6212, heteroresistant vancomycin-intermediate Staphylococcus aureus) and 2 μg/ml (R5599 and R5563). Trimethoprim-sulfamethoxazole MICs were ≤0.06/1.19 μg/ml. HD daptomycin plus trimethoprim-sulfamethoxazole displayed rapid bactericidal activity against SA H9749-1 (at 7 h) and R6212 (at 6 h) and bactericidal activity against R5599 (at 72 h) and R5563 (at 36 h). A ≥8 log(10) CFU/g decrease was observed with HD daptomycin plus trimethoprim-sulfamethoxazole against all strains (at 48 to 144 h), which was maintained with de-escalation to HD daptomycin or trimethoprim-sulfamethoxazole at 336 h. The combination for 14 days and the combination for 7 days de-escalated to HD daptomycin or trimethoprim-sulfamethoxazole was significantly better than daptomycin monotherapy (P < 0.05) and trimethoprim-sulfamethoxazole monotherapy (P < 0.05) at 168 and 336 h. Combination therapy followed by de-escalation offers a novel bactericidal therapeutic alternative for high-inoculum, serious DNS MRSA infections.

InternalMed_Harrison

No definitive trials have defined the best therapeutic algorithm for patients in whom TMP-SMX treatment for PCP is failing. If no other treatable infectious or noninfectious processes are detected and pulmonary dysfunction appears to be due to PCP alone, many authorities would switch from TMP-SMX to either IV pentamidine or IV clindamycin plus oral primaquine. Some authorities would add the second drug or drug combination to TMP-SMX rather than switching regimens. If patients are not already receiving them, glucocorticoids should be added to the regimen; the dosage and regimen, which are usually chosen empirically, depend on what glucocorticoid regimen (if any) the patient was receiving when PCP therapy was begun.

Haemophilus ducreyi

Pathogenesis H. ducreyi is an opportunistic microorganism that infects its host by way of breaks in the skin or epidermis. Inflammation then takes place as the area of infection is inundated with lymphocytes, macrophages, and granulocytes. This pyogenic inflammation causes regional lymphadenitis in the sexually transmitted disease chancroid. Diagnosis Although antigen detection, serology, and genetic amplification methods are sometimes used to diagnose infections with H. ducreyi and the genetic tests have greater sensitivity, they are not widely available, so cultures are currently considered the "gold standard" test. Treatment The first line treatments are one of four options : azithromycin 1 g orally in a single dose, ceftriaxone 250 mg intramuscularly in a single dose, ciprofloxacin 500 mg orally 2 times a day for 3 days, or erythromycin base 500 mg orally 3 times a day for 7 days. See also Sexually transmitted disease References

On the Treatment of <i>Pneumocystis jirovecii</i> Pneumonia: Current Practice Based on Outdated Evidence.

<iPneumocystis jirovecii</i pneumonia (PCP) is a common opportunistic infection causing more than 400000 cases annually worldwide. Although antiretroviral therapy has reduced the burden of PCP in persons with human immunodeficiency virus (HIV), an increasing proportion of cases occur in other immunocompromised populations. In this review, we synthesize the available randomized controlled trial (RCT) evidence base for PCP treatment. We identified 14 RCTs that were conducted 25-35 years ago, principally in 40-year-old men with HIV. Trimethoprim-sulfamethoxazole, at a dose of 15-20 mg/kg per day, is the treatment of choice based on historical practice rather than on quality comparative, dose-finding studies. Treatment duration is similarly based on historical practice and is not evidence based. Corticosteroids have a demonstrated role in hypoxemic patients with HIV but have yet to be studied in RCTs as an adjunctive therapy in non-HIV populations. The echinocandins are potential synergistic treatments in need of further investigation.

Optimizing Antimicrobial Dosing for Critically Ill Patients with MRSA Infections: A New Paradigm for Improving Efficacy during Continuous Renal Replacement Therapy.

The dosage regimen of vancomycin, teicoplanin and daptomycin remains controversial for critically ill patients undergoing continuous renal replacement therapy (CRRT). Monte Carlo simulation was applied to identify the optimal regimens of antimicrobial agents in patients with methicillin-resistant <iStaphylococcus aureus</i (MRSA) infections based on the mechanisms of different CRRT modalities on drug clearance. The optimal vancomycin dosage for patients received a CRRT doses ≤ 30 mL/kg/h was 20 mg/kg loading dose followed by 500 mg every 8 h, while 1 g every 12 h was appropriate when 35 mL/kg/h was prescribed. The optimal teicoplanin dosage under a CRRT dose ≤ 25 mL/kg/h was four loading doses of 10 mg/kg every 12 h followed by 10 mg/kg every 48 h, 8 mg/kg every 24 h and 6 mg/kg every 24 h for continuous veno-venous hemofiltration, continuous veno-venous hemodialysis and continuous veno-venous hemodiafiltration, respectively. When the CRRT dose increased to 30-35 mL/kg/h, the teicoplanin dosage should be increased by 30%. The recommended regimen for daptomycin was 6-8 mg/kg every 24 h under a CRRT dose ≤ 25 mL/kg/h, while 8-10 mg/kg every 24 h was optimal under 30-35 mg/kg/h. The CRRT dose has an impact on probability of target attainment and CRRT modality only influences teicoplanin.

InternalMed_Harrison

Culture Results Intensive Phase Continuation Phase Extension of Total Treatment Culture positive HRZE for 2 months, daily or intermit-HR for 4 months, daily or 5 d/wk To 9 months, if 2 months of Z is not completed or culture tent (with dose adjustment) or conversion is prolonged and cavitation is evident on plain radiographa HR for 4 months, intermittent (with dose adjustment) Culture negative HRZE for 2 months 2 months To 6 months, if patient is infected with HIV Extrapulmonary HRZE for 2 months HR for 4–7 months, daily or 5 d/wkb To 9–12 months in TB meningitis. Some recommend 9 months for bone/joint TB. Resistant to H QRZEc or, less often, RZES for 6 months … Prolonged culture conversion, cavitation Resistant to R HZEQc (IAd) for 2 months HEQ(S) for 10–16 months Prolonged culture conversion, delayed response

Amoxicillin -- Administration -- Amoxicillin Dosages

Adults: For adults, the recommended dosage of amoxicillin is 750 to 1750 mg/d, divided into doses and administered every 8 to 12 hours. Pediatric: For pediatric patients 3 months and older, the recommended amoxicillin dosage is 20 to 45 mg/kg/d, divided into doses and administered every 8 to 12 hours. H pylori infection (triple therapy): For the treatment of H pylori infection, the recommended dosing for triple therapy involves administering 1 g of amoxicillin, 500 mg of clarithromycin, and 30 mg of lansoprazole twice daily (every 12 hours) for 14 days. H pylori infection (dual therapy): For dual therapy against H pylori infection, the recommended dosing is 1 g of amoxicillin and 30 mg of lansoprazole, each administered 3 times daily.

InternalMed_Harrison

Of the currently available agents, trimethoprim-sulfamethoxazole (TMP-SMX) appears to be an effective alternative for treatment of TE in resource-poor settings where the preferred combination of pyrimethamine plus sulfadiazine is not available. The daily dose of TMP-SMX (one double-strength tablet) that is recommended as the preferred regimen for prophylaxis of PcP is effective against TE. If patients cannot tolerate TMP-SMX, the recommended alternative is dapsone-pyrimethamine, which likewise is effective against PcP. Atovaquone with or without pyrimethamine also can be considered. Prophylactic monotherapy with dapsone, pyrimethamine, azithromycin, clarithromycin, or aerosolized pentamidine is probably insufficient. AIDS patients who are seronegative for Toxoplasma and are not receiving prophylaxis for PcP should be retested for IgG antibody to Toxoplasma if their CD4+ T cell count drops to <100/µL. If seroconversion has taken place, then the patient should be given prophylaxis as

Vesicoureteral reflux

Medical treatment Medical treatment entails low dose antibiotic prophylaxis until resolution of VUR occurs. Antibiotics are administered nightly at half the normal therapeutic dose. The specific antibiotics used differ with the age of the patient and include: Amoxicillin or ampicillin – infants younger than 6 weeks Trimethoprim-sulfamethoxazole (co-trimoxazole) – 6 weeks to 2 months After 2 months the following antibiotics are suitable: Nitrofurantoin {5–7 mg/kg/24hrs} Nalidixic acid Bactrim Trimethoprim Cephalosporins Urine cultures are performed 3 monthly to exclude breakthrough infection. Annual radiological investigations are likewise indicated. Good perineal hygiene, and timed and double voiding are also important aspects of medical treatment. Bladder dysfunction is treated with the administration of anticholinergics.

[Not Available].

Rhodococcus equi is a facultative intracellular, obligate aerobe, partially acid fast, gram-positive pathogen that causes cavitary pneumonia in animals and immunocompromised humans. We describe 8 cases of R. equi pneumonia in patients with advanced HIV infection (CD4 counts less than 100/mm3), 7 males and 1 female (mean age 30.8 years), observed between 1991 and 1994. A history of exposure to farm animals was found in 4 patients. The most common presenting symptoms were fever, malaise, dyspnea, cough and hemoptysis, chest pain and weight loss. Chest x-rays showed tipical focal area of consolidation throughout the lung (3 upper, 3 lower and 2 middle fields) associated with cavitation in 4 cases. The definitive diagnosis in our hands was delayed only in the first case in which conflicting data resulted from blood culture (Bacillus sp. isolation) and sputum examen (acid-fast bacterium in the Ziehl-Neelsen stain). Final microbiological diagnosis depended on blood cultures (n=5), bronchoalveolar lavage (n=1), sputum (n=1), lung biopsy (n=1). All the patients were treated with prolonged courses of antibiotic therapy (259 days, range 120-340 in 6 dead patients; more than one year and two months respectively in two patients alive). According to microbial susceptibility TMP/SMX, vancomycin, imipenem, rifampin, aminoglycosides, macrolides and quinolons were more frequently used. Resistant R. equi mutants were selected during therapy with TMP/SMX (n=2), rifampin (n=1) and erythromycin (n=1). Five patient underwent pulmonary lobectomy after exclusion of metastatic bacterial lesions. Only 2 patients are alive, one after 365 days of antibiotic therapy and upper lung lobectomy, one after 60 days of antibiotic therapy. Optimal antimicrobial therapy and the role of surgery remain, in our experience, uncertain.

Creatine

Maintenance phase After the 5–7 day loading phase, muscle creatine stores are fully saturated and supplementation only needs to cover the amount of creatine broken down per day. This maintenance dose was originally reported to be around 2–3 g/day (or 0.03 g/kg/day), however, recent studies have suggested 3–5 g/day maintenance dose to maintain saturated muscle creatine. Absorption Endogenous serum or plasma creatine concentrations in healthy adults are normally in a range of 2–12 mg/L. A single 5 gram (5000 mg) oral dose in healthy adults results in a peak plasma creatine level of approximately 120 mg/L at 1–2 hours post-ingestion. Creatine has a fairly short elimination half life, averaging just less than 3 hours, so to maintain an elevated plasma level it would be necessary to take small oral doses every 3–6 hours throughout the day. Clearance It has been shown that once supplementation of creatine stops, muscle creatine stores return to baseline in 4–6 weeks.

InternalMed_Harrison

PART 2 Cardinal Manifestations and Presentation of Diseases Symptoms consistent with viral URI? Risk factors for HIV, gonorrhea? Group A Strep RADT or throat culture Penicillin allergy? No streptococcal testing Test accordingly Symptomatic management • Penicillin G 1.2 million units IM × 1, or • Penicillin VK 250 mg orally QID, or 500 mg orally BID, or • Amoxicillin 500 mg orally BID • Cephalexin 500 mg orally BID or TID (only if non-anaphylactic penicillin allergy), or • Azithromycin† 500 mg orally QD × 5 days, or • Clindamycin 300 mg orally TID Positive NoNegative* NOTE: All treatment durations are for 10 days with appropriate follow-up,unless otherwise specified.Yes Yes Yes No No No *Confirmation of a negative rapid antigen-detection test by a throat culture is not required in adults. †Macrolides do not treat F. necrophorum, a cause of pharyngitis in young adults (see text). Abbreviations: URI, upper respiratory infection; RADT, rapid antigen detection test

Severe sepsis caused by Arcanobacterium haemolyticum: a case report and review of the literature.

To describe a case of severe sepsis, cavitary pneumonia, and pyomyositis caused by Arcanobacterium haemolyticum. An 18-year-old male with a medical history significant for mild asthma presented to the emergency department complaining of a 7-day history of fever, diffuse myalgias, nausea, vomiting, diarrhea, and pain in his right upper quadrant, right shoulder, and left thigh. Cultures of blood, bronchoalveolar fluid, and surface and surgical swabs from the patient's left lower extremity grew A. haemolyticum. The patient was successfully treated with intravenous penicillin G 4 million units every 4 hours and azithromycin 500 mg once daily for 14 days. Within 36 hours after initiation of focused therapy, he became afebrile, pain decreased, and pulmonary symptoms abated. Oral azithromycin 500 mg/day for an additional 3 weeks was prescribed on discharge, and the patient showed no relapse at 2-month follow-up. A. haemolyticum is a weakly acid-fast, branching gram-positive bacillus most commonly implicated in pharyngitis in healthy adolescents and skin and soft-tissue infections in older, immunocompromised patients. Systemic infections are rarely reported in the literature. This organism remains susceptible to most classes of antimicrobials, including penicillins, cephalosporins, carbapenems, macrolides, tetracyclines, clindamycin, and vancomycin. Routine resistance has been reported only with trimethoprim/sulfamethoxazole. To our knowledge, there are no published case reports of severe sepsis caused by A. haemolyticum. While treatment options are numerous, we recommend the use of intravenous penicillin or a cephalosporin as first-line pharmacologic management of deep-seated infections caused by this rare organism.

InternalMed_Harrison

FIGuRE 226-33 A. Decrease in the incidence of opportunistic infections and Kaposi’s sarcoma in HIV-infected individuals with CD4+ T cell counts <100/μL from 1992 through 1998. (Adapted and updated from FJ Palella et al: N Engl J Med 338:853, 1998, and JE Kaplan et al: Clin Infect Dis 30[S1]:S5, 2000, with permission.) B. Quarterly incidence rates of cytomegalovirus (CMV), Pneumocystis jiroveci pneumonia (PCP), and Mycobacterium avium complex (MAC) from 1995 to 2001. (From FJ Palella et al: AIDS 16:1617, 2002.) plained fever for >2 weeks, and any patient with a recent history of oropharyngeal candidiasis. The preferred regimen for prophylaxis is TMP/SMX, one double-strength tablet daily. This regimen also provides protection against toxoplasmosis and some bacterial respiratory pathogens. For patients who cannot tolerate TMP/SMX, alternatives for prophylaxis include dapsone plus pyrimethamine plus leucovorin, aerosolized pentamidine administered by the Respirgard II nebulizer, and

The disposition of five therapeutically important antimicrobial agents in llamas.

The disposition of five therapeutic antimicrobial agents was studied in llamas (Lama glama) following intravenous bolus administration. Six llamas were each given ampicillin, tobramycin, trimethoprim, sulfamethoxazole, enrofloxacin and ceftiofur at a dose of 12 mg/kg, 1 mg/kg, 3 mg/kg, 15 mg/kg, 5 mg/kg, and 2.2 mg/kg of body weight, respectively, with a wash out period of at least 3 days between treatments. Plasma concentrations of these antimicrobial agents over 12 h following i.v. bolus dosing were determined by reverse phase HPLC. Disposition of the five antimicrobial agents was described by a two compartment open model with elimination from the central compartment, and also by non-compartmental methods. From compartmental analysis, the elimination rate constant, half-life, and apparent volume of distribution in the central compartment were determined. Statistical moment theory was used to determine noncompartmental pharmacokinetic parameters of mean residence time, clearance, and volume of distribution at steady state. Based on the disposition parameters determined, and stated assumptions of likely effective minimum inhibitory concentrations (MIC) a dose and dosing interval for each of five antimicrobial agents were suggested as 6 mg/kg every 12 h for ampicillin; 4 mg/kg once a day or 0.75 mg/kg every 8 h for tobramycin; 3.0 mg/kg/15 mg/kg every 12 h for trimethoprim/sulfamethoxazole; 5 mg/kg every 12 h for enrofloxacin; and 2.2 mg/kg every 12 h for ceftiofur sodium for llamas. Steady-state peak and trough plasma concentrations were also predicted for the drugs in this study for llamas.

Good outcome with trimethoprim 10 mg/kg/day-sulfamethoxazole 50 mg/kg/day for Pneumocystis jirovecii pneumonia in HIV infected patients.

Pneumocystis jirovecii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients is usually treated with trimethoprim (TMP)-sulfamethoxazole (SMX) 1920 mg 3 times daily (approximately equivalent to TMP 15 mg/kg/day-SMX 75 mg/kg/day) for 21 days. Pharmacokinetic data suggest that lower doses would be equally efficacious and might be associated with a lower incidence of adverse effects. We conducted a retrospective review of case notes for the first episode of laboratory-confirmed PCP in HIV-infected patients treated at Auckland City Hospital, from January 1991 through December 2007. Seventy-three of 84 (87%) patients were treated with TMP-SMX 960 mg 4 times daily or 3 times daily (approximately TMP 10 mg/kg/day-SMX 50 mg/kg/day). The overall mortality was 5/73 (7%). The mortality in patients with severe disease (transcutaneous oxygen saturation on admission < or =84%) was 3/16 (19%) and in patients admitted to the intensive care unit was 5/9 (56%). Fifteen of 73 (21%) patients required a change to an alternative treatment regimen because of adverse effects (rash in 10, rash plus fever in 3, neutropenia in 1, fever plus headache in 1). Treatment of PCP in adult HIV-infected patients with TMP-SMX 960 mg QID or TID appears to have comparable efficacy to treatment with higher doses and to be associated with a lower rate of treatment limiting adverse effects.

Histoplasma duboisii

Isolated lesions may be cleared by surgical removed, although some have been known to heal spontaneously. In contrast, deep lesions and disseminated disease require antifungal drug therapy. To date, no antifungal drug studies have specifically investigated the agent of African histoplasmosis. Hence most treatment approaches are based on the therapeutic strategies used to treat classical histoplasmosis caused by H. capsulatum. Amphotericin B is a mainstay of antifungal treatment, with a recommended dose of 1 mg/kg/day, culminating in a minimum dose of 2 g. Clinical response is typically apparent after 2 weeks of intravenous administration. Ketoconazole is also effective, starting at 600–800 mg/day for 3 months followed by a reduced dose of 400 mg/day for a further 6 months. The organism is also thought to be susceptible to fluconazole in vivo. A multi-month course of Amphotericin B followed by itraconazole has been suggested for complicated infection in immunodeficient individuals.

Austin Aztex U23

History

InternalMed_Harrison

Ampicillin 300 (mg/kg)/d, q6h 12 g/d, q4h Cefepime 150 (mg/kg)/d, q8h 6 g/d, q8h Cefotaxime 225-300 (mg/kg)/d, q6h 12 g/d, q4h Ceftriaxone 100 (mg/kg)/d, q12h 4 g/d, q12h Ceftazidime 150 (mg/kg)/d, q8h 6 g/d, q8h Gentamicin 7.5 (mg/kg)/d, q8hb 7.5 (mg/kg)/d, q8h Meropenem 120 (mg/kg)/d, q8h 6 g/d, q8h Metronidazole 30 (mg/kg)/d, q6h 1500–2000 mg/d, q6h Nafcillin 100–200 (mg/kg)/d, q6h 9–12 g/d, q4h Penicillin G 400,000 (U/kg)/d, q4h 20–24 million U/d, q4h Vancomycin 45-60 (mg/kg)/d, q6h 45-60 (mg/kg)d, q6–12hb aAll antibiotics are administered intravenously; doses indicated assume normal renal and hepatic function. bDoses should be adjusted based on serum peak and trough levels: gentamicin therapeutic level: peak: 5–8 μg/mL; trough: <2 μg/mL; vancomycin therapeutic level: peak: 25–40 μg/mL; trough: 5–15 μg/mL. Meningitis, Encephalitis, Brain Abscess, and Empyema White blood cells 10/μL to 10,000/μL; neutrophils predominate Glucose <2.2 mmol/L (<40 mg/dL) CSF/serum glucose <0.4

Pralidoxime

Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor blood–brain barrier penetration, it has little effect on centrally-mediated respiratory depression. Atropine, which is choice of drug to antagonise the muscarinic effects of organophosphates, is administered even before pralidoxime during the treatment of organophosphate poisoning. While the efficacy of atropine has been well-established, clinical experience with pralidoxime has led to widespread doubt about its efficacy in treatment of organophosphorus poisoning. Dosage Adults: 30 mg/kg (typically 1–2 g), administered by intravenous therapy over 15–30 minutes, repeated 60 minutes later. It can also be given as a 500 mg/h continuous IV infusion. Children: 20–50 mg/kg followed by a maintenance infusion at 5–10 mg/kg/h. Intravenous infusions can lead to respiratory or cardiac arrest if given too quickly.

[The treatment of pulmonary tuberculosis in a special hospital. Its evolution from 1948 to 1986].

Nine hundred and sixty six patients diagnosed of pulmonary and/or pleural tuberculosis and admitted to a specialized hospital from 1948 to 1986, have been retrospectively analyzed, investigating their treatment and evolution. Sixty two percent of patients did not fulfil pharmaceutical treatment as far as number and dose of drugs, evolving through the decades (50, 60, 70, and 80s) with a 100%, 82%, 37% and 3% respectively. A 13% of patients did not receive any chemotherapy, 16% underwent surgery, and 53% received a second treatment. Real or hidden monotherapy was given to 38% of patients. Isoniazide has been the most uniformly used drug. Streptomycin has been the most frequently underdosed used drug. Sputum culture turned negative in 42% and 51% of patients during the first 3 and 6 months respectively, with a 42% of positives persisting after one year and a 30% when discharged. A statistically significant difference is observed when comparing all the variables between admitted patients up to 1969 and from 69 to 86 in favor of the second period.

Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days.

The efficacy of the traditionally recommended ampicillin (Amp) plus gentamicin (GM) regimen was compared with that of a trimethoprim-sulfamethoxazole (TMP/SMZ)-plus-GM regimen and the adequacy of 14 days total therapy for acute uncomplicated pyelonephritis (AUPN). Eighty-five women hospitalized for AUPN were randomly assigned to receive either Amp, 1 g intravenously (iv) every 6 h for 3 days, then 500 mg orally four times daily, or TMP/SMZ, 160/800 mg iv every 12 h for 3 days, then 160/800 mg orally twice daily. Initially, all patients also received GM every 8 h iv (mean, 606 doses). Antimicrobial resistance necessitated modifying therapy of 14 (32%) of the Amp recipients but of none of the TMP/SMZ recipients (P less than .001). Both regimens produced a satisfactory bacteriologic and clinical response in all cases. Reinfection occurred in 11% of Amp and in 8% of TMP/SMZ recipients. No patient experienced relapsing infection. The TMP/SMZ regimen was less costly and less likely to require modification due to antimicrobial resistance.

InternalMed_Harrison

Resistant to methicillin Clindamycin (300–450 mg/kg tid), Same options as under “Drug of It is important to know the antibiotic susceptibility of TMP-SMX (1 or 2 ds tablets bid), mino-Choice” isolates in the specific geographic region. All draincycline or doxycycline (100 mg q12hb), age should be cultured. linezolid (600 mg bid) or tedizolid (200 mg once daily) aRecommended dosages are for adults with normal renal and hepatic function. bThe dosage must be adjusted for patients with reduced creatinine clearance. cFor the treatment of prosthetic-valve endocarditis, the addition of gentamicin (1 mg/kg q8h) and rifampin (300 mg PO q8h) is recommended, with adjustment of the gentamicin dosage if the creatinine clearance rate is reduced. dDaptomycin cannot be used for the treatment of pneumonia. eVancomycin-resistant S. aureus isolates from clinical infections have been reported.

InternalMed_Harrison

Vancomycin, 15 mg/kg q12hb; Ceftriaxone, 2 g q12h; Metronidazole, 500 mg q8h Vancomycin, 15 mg/kg q12hb; Ceftriaxone, 2 g q12h Azithromycin, 500 mg PO × 1, then 250 mg PO qd × 4 days A respiratory fluoroquinolone (moxifloxacin, 400 mg IV/PO qd; gemifloxacin, 320 mg PO qd; or levofloxacin, 750 mg IV/PO qd); A β-lactam (cefotaxime, ceftriaxone, or ampicillinsulbactam) plus azithromycin Azithromycin or a respiratory fluoroquinolone An antipseudomonal β-lactam (cefepime, 1–2 g q8–12 h; ceftazidime, 2 g q8h; imipenem, 1 g q8h; meropenem, 1 g q8h; or piperacillin-tazobactam, 4.5 g q6h); An antipseudomonal fluoroquinolone (levofloxacin or ciprofloxacin, 400 mg q8h) or an aminoglycoside (amikacin, 20 mg/kg q24hc; gentamicin, 7 mg/kg q24he; or tobramycin, 7 mg/kg q24he) Cefoxitin, 2 g q6h; A combination of metronidazole (500 mg q8–12h) plus cefazolin (1–2 g q8h) or cefuroxime (1.5 g q8h) or ceftriaxone (1–2 g q12–24h) or cefotaxime (1–2 g q6–8h)