Christopher A. Schriever

Sex-Related Differences in the Pharmacokinetics of Once-Daily Saquinavir Soft-Gelatin Capsules Boosted with Low-Dose Ritonavir in Patients Infected with Human Immunodeficiency Virus Type 1

Study Objectives. To compare the steady‐state pharmacokinetics and safety of saquinavir soft‐gelatin capsules (SGC) plus low‐dose ritonavir administered once/day in antiretroviral‐naïve adult patients infected with the human immunodeficiency virus type 1 (HIV‐1) and to evaluate any sex‐related differences.

Pharmacokinetics and Pharmacodynamics of Intravenous Levofloxacin at 750 Milligrams and Various Doses of Metronidazole in Healthy Adult Subjects

ABSTRACT The purpose of this investigation was to evaluate the steady-state pharmacokinetics, pharmacodynamics, and safety of intravenous levofloxacin at 750 mg administered once daily combined with three different dosages of intravenous metronidazole (500 mg every 8 h [q8h], 1,000 mg q24h, and 1,500 mg q24h). Eighteen healthy adult subjects received all three combinations in a randomized, crossover fashion. Serial blood and urine samples were collected on the third day of each study period. The 24-h areas under the inhibitory (AUIC0-24) and bactericidal (AUBC0-24) curves of these three combination regimens were determined against clinical isolates of Bacteroides fragilis, Bacteroides thetaiotaomicron, Peptostreptococcus asaccharolyticus, and Escherichia coli. The mean concentrations of levofloxacin were not different between study periods and were similar to those previously published. The mean (± standard deviation) areas under the metronidazole plasma concentration-time curve (AUC0-24) for 1,500-mg q24h (338 ± 105 mg · h/liter) and 500-mg q8h (356 ± 68 mg · h/liter) regimens were not different (P > 0.05), but both were significantly higher than the 1,000-mg q24h AUC0-24 (P < 0.05, 227 ± 57 mg · h/liter). Mean (± standard deviation) total body clearance and renal clearance values were similar among the 500-mg q8h, 1,000-mg q24, and 1,500-mg q24h regimens (62 ± 7, 67 ± 13, and 67 ± 14 and 11 ± 3, 12 ± 2, and 12 ± 5 ml/min/1.73 m2, respectively). Levofloxacin at 750 mg q24h plus metronidazole at 500 mg q8h or 1,500 mg q24h resulted in similar AUIC0-24 and AUBC0-24 values with one exception: the AUIC0-24 for the 1,500-mg q24h regimen against B. thetaiotamicron was significantly higher (P < 0.05) than those of the other regimens. Overall, the combination of levofloxacin at 750 mg once daily and metronidazole at 500 mg q8h or 1,500 mg q24h appeared to have greater AUIC0-24 and AUBC0-24 values than did the 1,000-mg q24h regimen. All combination regimens of levofloxacin and metronidazole were well tolerated, and no serious drug-related adverse effects were reported. The pharmacokinetic, safety, and pharmacodynamic data from our study suggest that a once-daily regimen of intravenous levofloxacin at 750 mg and metronidazole at 1,500 mg warrants further clinical investigation.

The IS6110 repetitive DNA element of Mycobacterium tuberculosis is not detected in exhaled breath condensate of patients with active pulmonary tuberculosis

Background: A large tertiary referral hospital in inner-city Chicago. Objectives: To determine whether the IS6110 repetitive DNA element of Mycobacterium tuberculosis is detected in exhaled breath condensate of patients with newly diagnosed active pulmonary tuberculosis. Methods: Ten hospitalized patients with positive Ziehl-Neelson-stained sputum smears were studied. Concurrent sputum cultures for mycobacteria were performed as well. Exhaled breath condensate was collected from each patient within 6 days of initiating antituberculosis chemotherapy (median 1.5 days). These samples were analyzed by polymerase chain reaction (PCR) using primers designed to amplify the IS6110 DNA fragment of M. tuberculosis. Exogenous M. tuberculosis DNA was added to exhaled breath condensate samples to detect PCR inhibitors. Concurrent cultures of exhaled breath condensate for mycobacteria were performed. Results:M. tuberculosis was identified in 9 of 10 sputum cultures. One isolate was identified as Mycobacterium kansasii. The IS6110 repetitive DNA element of M. tuberculosis was not detected in any of the 10 exhaled breath condensate samples. Exogenous M. tuberculosis DNA added to these samples elicited the characteristic band pattern of M. tuberculosis on agarose gel electrophoresis. No PCR inhibitors were detected. Cultures of exhaled breath condensate showed no growth of mycobacteria. Conclusions: The IS6110 repetitive DNA element of M. tuberculosis is not detected in exhaled breath condensate of patients with newly diagnosed active pulmonary tuberculosis.

In vitro bactericidal activity of piperacillin, gentamicin, and metronidazole in a mixed model containing Escherichia coli, Enterococcus faecalis, and Bacteroides fragilis

An anaerobic, mixed model assay was used to study the bactericidal activities of piperacillin, gentamicin, and metronidazole, alone and in double- and triple-antibiotic combinations against a polymicrobial suspension of E. coli, E. faecalis, and B. fragilis. Only slight differences were noted with the agents when tested against single (10(5) cfu/mL inoculum) versus polymicrobic suspensions (10(6) cfu/mL final inoculum) of susceptible and resistant organisms. Contrary to previous reports in the literature, metronidazole was not active against E. coli in an anaerobic environment (even in the presence of B. fragilis) nor was the activity of metronidazole reduced against B. fragilis in the presence of E. faecalis. Gentamicin demonstrated excellent activity against E. coli when tested in a Bactron anaerobic chamber (5% hydrogen, 5% CO(2,) 90% nitrogen). The pH of the media was only reduced to 6.3-6.7, considerably higher than the pH range of 5-6 needed to significantly reduce the activity of aminoglycosides.

Postantibiotic Effects and Bactericidal Activities of Clarithromycin–14-Hydroxy-Clarithromycin, versus Those of Amoxicillin-Clavulanate, against Anaerobes

ABSTRACT The bactericidal activities and postantibiotic effects (PAE) of clarithromycin–14-hydroxy-clarithromycin and amoxicillin-clavulanate against Bacteroides fragilis and Peptostreptococcus anaerobius were determined. A concentration of twice the MIC resulted in bactericidal activity against four of four and three of four organisms at 24 h with clarithromycin–14-hydroxy-clarithromycin and amoxicillin-clavulanate, respectively. The PAE of clarithromycin–14-hydroxy-clarithromycin was 1.44 to 3.20 h, compared to the less than 1 h of amoxicillin-clavulanate. Clarithromycin–14-hydroxy-clarithromycin possesses good activity against susceptible anaerobes.

Sustained viral suppression with co-administration of oxcarbazepine and dolutegravir

Co-administration of dolutegravir and oxcarbazepine has been reported to reduce levels of dolutegravir and therefore is contraindicated due to insufficient data to make dosing recommendations. We present eight cases in which patients with human immunodeficiency virus (HIV) inadvertently received oxcarbazepine while concurrently receiving 50 mg of dolutegravir daily as part of their antiretroviral therapy. Upon further evaluation, lab results revealed that despite the risk of decreased levels of dolutegravir due to possible oxcarbazepine enzyme induction, patients maintained at or near virologic suppression (viral load <20 copies/ml). Suppression was maintained in patients virally suppressed prior to oxcarbazepine initiation as well as in patients receiving high doses of oxcarbazepine (>1200 mg). All patients self-reported complete adherence to oxcarbazepine and dolutegravir. Furthermore, careful review of additional patient medications suggested no other identifiable drug interactions that could have affected their antiretroviral therapy. This case series suggests that despite the well-documented drug interaction, concomitant administration of oxcarbazepine and dolutegravir in the clinical setting did not adversely affect viral suppression in patients with HIV.

Fostering Interprofessional Education Through a Multidisciplinary, Community-Based Pandemic Mass Vaccination Exercise

We expanded health care services to economically disadvantaged individuals in an interprofessional, student-driven vaccination effort that also served as a pandemic planning drill. Health care professional students from colleges in and around Rockford, Illinois participated in implementing a mass vaccination event from 2011 to 2014 that targeted the underserved population. There was a 459% increase in total vaccinations administered to at-risk patients from year 1 to year 4. This interprofessional health care student-driven effort expanded medical service to disadvantaged individuals.

Considerations for the Management of Gram-Positive Pathogens in the Intensive Care Unit

Surveillance data demonstrate that the majority of gram-positive bacterial isolates obtained in the intensive care unit (ICU) setting are staphylococci and enterococci. Staphylococci, mainly Staphylococcus aureus and coagulase-negative staphylococci, compose the majority of clinical isolates. Data from 25 North American ICUs reported methicillin-resistant Saureus (MRSA) in more than 50% of the Saureus organisms isolated mainly from a respiratory source. In addition to MRSA, Saureus with reduced susceptibility to vancomycin has been reported. Enterococci are typically considered opportunistic pathogens, infecting immunocompromised hosts. Resistance of enterococci to vancomycin, along with the newer gram-positive antimicrobials, is an increasing problem. Investigators have demonstrated that nearly 30% of enterococci isolated in the ICU are resistant to vancomycin. The high level of resistance and limited therapeutic options make treating resistant gram-positive organisms such as MRSA and vancomycin-resistant enterococci particularly problematic. While vancomycin has long been considered the gold standard for the treatment of resistant gram-positive infections, newer agents (eg, quinupristin-dalfopristin, linezolid, and daptomycin) offer therapeutic alternatives.