R J Hamill

Baylor College of Medicine, Houston, TX, United States

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Publications (111)705.05 Total impact

  • Richard J Hamill
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    ABSTRACT: Because of the increasing prevalence and changing microbiological spectrum of invasive fungal infections, some form of amphotericin B still provides the most reliable and broad spectrum therapeutic alternative. However, the use of amphotericin B deoxycholate is accompanied by dose-limited toxicities, most importantly, infusion-related reactions and nephrotoxicity. In an attempt to improve the therapeutic index of amphotericin B, three lipid-associated formulations were developed, including amphotericin B lipid complex (ABLC), liposomal amphotericin B (L-AmB), and amphotericin B colloidal dispersion (ABCD). The lipid composition of all three of these preparations differs considerably and contributes to substantially different pharmacokinetic parameters. ABLC is the largest of the lipid preparations. Because of its size, it is taken up rapidly by macrophages and becomes sequestered in tissues of the mononuclear phagocyte system such as the liver and spleen. Consequently, compared with the conventional formulation, it has lower circulating amphotericin B serum concentrations, reflected in a marked increase in volume of distribution and clearance. Lung levels are considerably higher than those achieved with other lipid-associated preparations. The recommended therapeutic dose of ABLC is 5 mg/kg/day. Because of its small size and negative charge, L-AmB avoids substantial recognition and uptake by the mononuclear phagocyte system. Therefore, a single dose of L-AmB results in a much higher peak plasma level (Cmax) than conventional amphotericin B deoxycholate and a much larger area under the concentration-time curve. Tissue concentrations in patients receiving L-AmB tend to be highest in the liver and spleen and much lower in kidneys and lung. Recommended therapeutic dosages are 3-6 mg/kg/day. After intravenous infusion, ABCD complexes remain largely intact and are rapidly removed from the circulation by cells of the macrophage phagocyte system. On a milligram-to-milligram basis, the Cmax achieved is lower than that attained by conventional amphotericin B, although the larger doses of ABCD that are administered produce an absolute level that is similar to amphotericin B. ABCD exhibits dose-limiting, infusion-related toxicities; consequently, the administered dosages should not exceed 3-4 mg/kg/day. The few comparative clinical trials that have been completed with the lipid-associated formulations have not demonstrated important clinical differences among these agents and amphotericin B for efficacy, although there are significant safety benefits of the lipid products. Furthermore, only one published trial has ever compared one lipid product against another for any indication. The results of these trials are particularly difficult to interpret because of major heterogeneities in study design, disease definitions, drug dosages, differences in clinical and microbiological endpoints as well as specific outcomes examined. Nevertheless, it is possible to derive some general conclusions given the available data. The most commonly studied syndrome has been empiric therapy for febrile neutropenic patients, where the lipid-associated preparations did not appear to provide a survival benefit over conventional amphotericin B deoxycholate, but did offer a significant advantage for the prevention of various breakthrough invasive fungal infections. For treatment of documented invasive fungal infections that usually involved hematological malignancy patients, no individual randomized trial has demonstrated a mortality benefit due to therapy with one of the lipid formulations. Results from meta-analyses have been contradictory, with one demonstrating a mortality benefit from all-cause mortality and one that did not demonstrate a mortality benefit. In the only published study to examine HIV-infected patients with disseminated histoplasmosis, clinical success and mortality were significantly better with L-AmB compared with amphotericin B deoxycholate; there were no differences in microbiological outcomes between treatment groups. The lipid-associated preparations were not significantly better than amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis for either clinical or microbiological outcomes that were studied. In all of the trials that specifically examined renal toxicity, the lipid-associated formulations were significantly less nephrotoxic than amphotericin B deoxycholate. Infusion-related reactions occurred less frequently with L-AmB when compared with amphotericin B deoxycholate; however, ABCD had equivalent or more frequent infusion-related reactions than conventional amphotericin B, and this resulted in the cessation of at least one clinical trial. At the present time, this particular lipid formulation is no longer commercially available. For the treatment of most invasive fungal infections, an amphotericin B lipid formulation provides a safer alternative than conventional amphotericin B, with at least equivalent efficacy. As the cost of therapy with these agents continues to decline, these drugs will likely maintain their important role in the antifungal drug armamentarium because of their efficacy and improved safety profile.
    Drugs 06/2013; · 4.13 Impact Factor
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    ABSTRACT: Current efforts to understand antibiotic resistance on the whole genome scale tend to focus on known genes even as high throughput sequencing strategies uncover novel mechanisms. To identify genomic variations associated with antibiotic resistance, we employed a modified genome-wide association study; we sequenced genomic DNA from pools of E. coli clinical isolates with similar antibiotic resistance phenotypes using SOLiD technology to uncover single nucleotide polymorphisms (SNPs) unanimously conserved in each pool. The multidrug-resistant pools were genotypically similar to SMS-3-5, a previously sequenced multidrug-resistant isolate from a polluted environment. The similarity was evenly spread across the entire genome and not limited to plasmid or pathogenicity island loci. Among the pools of clinical isolates, genomic variation was concentrated adjacent to previously reported inversion and duplication differences between the SMS-3-5 isolate and the drug-susceptible laboratory strain, DH10B. SNPs that result in non-synonymous changes in gyrA (encoding the well-known S83L allele associated with fluoroquinolone resistance), mutM, ligB, and recG were unanimously conserved in every fluoroquinolone-resistant pool. Alleles of the latter three genes are tightly linked among most sequenced E. coli genomes, and had not been implicated in antibiotic resistance previously. The changes in these genes map to amino acid positions in alpha helices that are involved in DNA binding. Plasmid-encoded complementation of null strains with either allelic variant of mutM or ligB resulted in variable responses to ultraviolet light or hydrogen peroxide treatment as markers of induced DNA damage, indicating their importance in DNA metabolism and revealing a potential mechanism for fluoroquinolone resistance. Our approach uncovered evidence that additional DNA binding enzymes may contribute to fluoroquinolone resistance and further implicate environmental bacteria as a reservoir for antibiotic resistance.
    PLoS ONE 01/2013; 8(6):e65961. · 3.53 Impact Factor
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    ABSTRACT: Antibiotic-resistant infections caused by gram-negative bacteria are a major healthcare concern. Repurposing drugs circumvents the time and money limitations associated with developing new antimicrobial agents needed to combat these antibiotic-resistant infections. Here we identified the off-patent antifungal agent, ciclopirox, as a candidate to repurpose for antibiotic use. To test the efficacy of ciclopirox against antibiotic-resistant pathogens, we used a curated collection of Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae clinical isolates that are representative of known antibiotic resistance phenotypes. We found that ciclopirox, at 5-15 µg/ml concentrations, inhibited bacterial growth regardless of the antibiotic resistance status. At these same concentrations, ciclopirox reduced growth of Pseudomonas aeruginosa clinical isolates, but some of these pathogens required higher ciclopirox concentrations to completely block growth. To determine how ciclopirox inhibits bacterial growth, we performed an overexpression screen in E. coli. This screen revealed that galE, which encodes UDP-glucose 4-epimerase, rescued bacterial growth at otherwise restrictive ciclopirox concentrations. We found that ciclopirox does not inhibit epimerization of UDP-galactose by purified E. coli GalE; however, ΔgalU, ΔgalE, ΔrfaI, or ΔrfaB mutant strains all have lower ciclopirox minimum inhibitory concentrations than the parent strain. The galU, galE, rfaI, and rfaB genes all encode enzymes that use UDP-galactose or UDP-glucose for galactose metabolism and lipopolysaccharide (LPS) biosynthesis. Indeed, we found that ciclopirox altered LPS composition of an E. coli clinical isolate. Taken together, our data demonstrate that ciclopirox affects galactose metabolism and LPS biosynthesis, two pathways important for bacterial growth and virulence. The lack of any reported fungal resistance to ciclopirox in over twenty years of use in the clinic, its excellent safety profiles, novel target(s), and efficacy, make ciclopirox a promising potential antimicrobial agent to use against multidrug-resistant problematic gram-negative pathogens.
    PLoS ONE 01/2013; 8(7):e69646. · 3.53 Impact Factor
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    ABSTRACT: An 81-year-old man is presented who developed cryptococcal infection after treatment for Clostridium difficile infection.
    Dermatology online journal 01/2013; 19(10):20024.
  • Daniel B Aruch, Yogesh Bhusal, Richard J Hamill
    The American journal of medicine 07/2011; 124(7):e7-8. · 5.30 Impact Factor
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    ABSTRACT: BACKGROUND. It is generally acknowledged that amphotericin B is the most effective treatment for cryptococcal meningitis. However, administration of this drug is accompanied by substantial adverse effects. This double-blind study, performed before the routine availability of highly active antiretroviral therapy, was designed to compare the efficacy and safety of liposomal amphotericin B to conventional amphotericin deoxycholate in patients with acquired immunodeficiency syndrome (AIDS) and acute cryptococcal meningitis. METHODS. Patients were randomized (ratio, 1:1:1) from multiple sites in the United States and Canada to receive either amphotericin B at 0.7 mg/kg/day (n = 87), liposomal amphotericin B at 3 mg/kg/day (n = 86), or liposomal amphotericin B at 6 mg/kg/day (n = 94). RESULTS. Efficacy was similar among all 3 treatment groups. The overall incidence of infusion-related reactions was significantly lower for both the 3 mg/kg/day and 6 mg/kg/day dosages of liposomal amphotericin B, compared with conventional amphotericin B (P < .001). Significantly fewer patients who received the 3 mg/kg/day dosage of liposomal amphotericin B developed nephrotoxicity, indicated by a doubling of the serum creatinine value, compared with recipients of conventional amphotericin B (P = .004). Overall mortality at 10 weeks was 11.6%, with no significant differences among the treatment groups. CONCLUSIONS. Liposomal amphotericin B provides an equally efficacious alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis. Liposomal amphotericin B at a dosage of 3 mg/kg/day is accompanied by significantly fewer adverse effects.
    Clinical Infectious Diseases 07/2010; 51(2):225-32. · 9.37 Impact Factor
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    ABSTRACT: Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.
    Clinical Infectious Diseases 02/2010; 50(3):291-322. · 9.37 Impact Factor
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    ABSTRACT: Itraconazole is the preferred drug for chronic maintenance therapy in HIV-infected patients with disseminated histoplasmosis. Unfortunately, few clinical data exist confirming a presumed interaction between itraconazole and nonnucleoside reverse transcriptase inhibitors (NNRTIs). To determine whether serum itraconazole concentrations are affected by the type of antiretroviral therapy (NNRTI or protease inhibitor [PI]) being taken concomitantly. This retrospective cohort identified patients on antiretroviral therapy and itraconazole for disseminated histoplasmosis between January 2003 and December 2006 at a large HIV clinic in Houston, TX. Available laboratory values were abstracted from medical records. Thirteen itraconazole concentrations from 10 patients were available for analysis: 7 patients were on concomitant PIs, 4 on concomitant NNRTIs, and 2 on antiretroviral regimens containing both PIs and NNRTIs. Six of the itraconazole concentrations during concomitant PI treatment were therapeutic (>1.0 microg/mL), in contrast with none in patients taking an NNRTI. All patients taking concomitant NNRTIs had undetectable serum itraconazole concentrations (<0.05 microg/mL). Two patients switched from NNRTI-based to PI-based antiretroviral regimens and subsequently reached therapeutic itraconazole concentrations. Although limited by small sample size, this study provides the largest clinical data among HIV-infected patients demonstrating that coadministration of an NNRTI and itraconazole results in significant decreases in itraconazole blood concentrations, likely by inducing the CYP3A4 enzyme system. Itraconazole concentrations should be monitored in patients taking concomitant NNRTIs. PI-based highly active antiretroviral therapy (HAART) may be preferred over NNRTI-based HAART when itraconazole is used to treat HIV-infected patients with disseminated histoplasmosis.
    Annals of Pharmacotherapy 04/2009; 43(5):908-13. · 2.92 Impact Factor
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    ABSTRACT: Fluoroquinolones are some of the most prescribed antibiotics in the United States. Previously, we and others showed that the fluoroquinolones exhibit a class effect with regard to the CLSI-established breakpoints for resistance, such that decreased susceptibility (i.e., an increased MIC) to one fluoroquinolone means a simultaneously decreased susceptibility to all. For defined strains, however, clear differences exist in the pharmacodynamic properties of each fluoroquinolone and the extent to which resistance-associated genotypes affect the MICs of each fluoroquinolone. In a pilot study of 920 clinical Escherichia coli isolates, we uncovered tremendous variation in norfloxacin MICs. The MICs for all of the fluoroquinolone-resistant isolates exceeded the resistance breakpoint, reaching 1,000 microg/ml. Approximately 25% of the isolates (n = 214), representing the full range of resistant norfloxacin MICs, were selected for the simultaneous determinations of ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs. We found that (i) great MIC variation existed for all four fluoroquinolones, (ii) the ciprofloxacin and levofloxacin MICs of >90% of the fluoroquinolone-resistant isolates were higher than the resistance breakpoints, (iii) ciprofloxacin and levofloxacin MICs were distributed into two distinct groups, (iv) the MICs of two drug pairs (ciprofloxacin and norfloxacin by Kendall's Tau-b test and gatifloxacin and levofloxacin by paired t test) were similar with statistical significance but were different from each other, and (v) approximately 2% of isolates had unprecedented fluoroquinolone MIC relationships. Thus, although the fluoroquinolones can be considered equivalent with regard to clinical susceptibility or resistance, fluoroquinolone MICs differ dramatically for fluoroquinolone-resistant clinical isolates, likely because of differences in drug structure.
    Antimicrobial Agents and Chemotherapy 10/2008; 53(1):229-34. · 4.57 Impact Factor
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    Michail S Lionakis, Richard J Hamill
    Canadian Medical Association Journal 06/2008; 178(10):1289-91. · 6.47 Impact Factor
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    ABSTRACT: Escherichia coli infections are common and often treated with fluoroquinolones. Fluoroquinolone resistance is of worldwide importance and is monitored by national and international surveillance networks. In this study, we analyzed the effects of time, culture site, and patient age, sex, and location on fluoroquinolone resistance in E. coli clinical isolates. To understand how patient factors and time influenced fluoroquinolone resistance and to determine how well data from surveillance networks predict trends at Ben Taub General Hospital in Houston, TX, we used Perl to parse and MySQL to house data from antibiograms (n congruent with 21,000) for E. coli isolated between 1999 to 2004 using Chi Square, Bonferroni, and Multiple Linear Regression methods. Fluoroquinolone resistance (i) increased with time; (ii) exceeded national averages by 2- to 4-fold; (iii) was higher in males than females, largely because of urinary isolates from male outpatients; (iv) increased with patient age; (v) was 3% in pediatric patients; (vi) was higher in hospitalized patients than outpatients; (vii) was higher in sputum samples, particularly from inpatients, than all other culture sites, including blood and urine, regardless of patient location; and (viii) was lowest in genital isolates than all other culture sites. Additionally, the data suggest that, with regard to susceptibility or resistance by the Dade Behring MicroScan system, a single fluoroquinolone suffices as a "surrogate marker" for all of the fluoroquinolone tested. Large surveillance programs often did not predict E. coli fluoroquinolone resistance trends at a large, urban hospital with a largely indigent, ethnically diverse patient population or its affiliated community clinics.
    BMC Infectious Diseases 02/2008; 8:4. · 3.03 Impact Factor
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    ABSTRACT: A pilot candidate gene association study was conducted to investigate the role of three common functional genetic polymorphisms of the low-affinity Fc gamma receptors, FCGR2A (131H/R), FCGR3A (158F/V) and FCGR3B (NA1/NA2) in Cryptococcus neoformans infections in individuals not infected with HIV. The FCGR2A 131RR and FCGR3A 158VV genotypes were over-represented [OR: 1.67 (1.05-2.63) and 2.04 (1.06-4.00), respectively] whereas the FCGR3B NA2NA2 was under-represented in patients with cryptococcosis (28% vs. 40% in controls). An analysis of haplotypes showed a significant difference in distribution between cases and controls overall and in Caucasians.
    Medical Mycology 10/2007; 45(6):513-8. · 1.98 Impact Factor
  • Hoonmo L Koo, Richard J Hamill, Roberto A Andrade
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    ABSTRACT: Although there is a presumed drug-drug interaction between itraconazole and nonnucleoside reverse-transcriptase inhibitors, the medical literature lacks such documentation. We describe a drug-drug interaction between itraconazole and efavirenz in a patient with disseminated histoplasmosis and acquired immunodeficiency syndrome (AIDS). The drug combination resulted in persistently elevated urinary Histoplasma antigen levels and subtherapeutic plasma itraconazole concentrations. Changing treatment from efavirenz to a protease inhibitor was accompanied by improvements in the desired urinary Histoplasma antigen level and plasma itraconazole concentration.
    Clinical Infectious Diseases 10/2007; 45(6):e77-9. · 9.37 Impact Factor
  • Divay Chandra, Sachin Gupta, Richard Hamill
    The American journal of medicine 06/2007; 120(5):e7; author reply e9. · 5.30 Impact Factor
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    ABSTRACT: Clostridium difficile-associated disease has increased in incidence and severity. Recommended treatments include metronidazole and vancomycin. Recent investigations, however, document the failure of metronidazole to cure a substantial proportion of patients with Clostridium difficile colitis, but oral administration of vancomycin raises concerns over selection of antibiotic-resistant organisms in the hospital environment. We have recently shown that nitazoxanide is as effective as metronidazole in initial therapy for C. difficile colitis. We hypothesized that this drug might be effective in treating patients who fail therapy with metronidazole. In the present study, we identified 35 patients who failed treatment with metronidazole for C. difficile colitis; failure was defined as either no improvement in symptoms or signs of disease (28 patients) after >or= 14 days of treatment with metronidazole or prompt recurrence on at least two occasions after initially responding to such treatment (seven patients). These patients were ill with numerous co-morbidities. Nitazoxanide, 500 mg twice daily, was given for 10 days; results from all patients are included. Twenty-six (74%) of 35 patients responded to nitazoxanide, of whom seven later had recurrent disease, yielding a cure rate of 19 of 35 (54%) from initial therapy. Three who initially failed and one who had recurrent disease were re-treated with, and responded to, nitazoxanide. Thus, the aggregate cure with nitazoxanide in this difficult-to-treat population was 23 of 35 (66%). Nitazoxanide appears to provide effective therapy for patients with C. difficile colitis who fail treatment with metronidazole.
    Journal of Antimicrobial Chemotherapy 04/2007; 59(4):705-10. · 5.34 Impact Factor
  • Clinical Infectious Diseases 01/2007; 44(1):152-154. · 9.37 Impact Factor
  • Richard J Hamill
    Clinical Infectious Diseases 11/2006; 43(8):1074-6. · 9.37 Impact Factor
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    ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with community-associated infection have been described as strains genetically distinct from the strains isolated from patients with healthcare-associated infection. This study examines the hypothesis that community-associated MRSA (CA-MRSA) strains now cause serious infections in hospitalized patients. Thirty-seven clinical MRSA isolates were randomly selected from blood isolates obtained from July 2003 through June 2004. Strains were tested for staphylococcal chromosomal cassette mec (SCCmec) type, pulsed-field gel electrophoresis (PFGE) type, and presence of Panton-Valentine leukocidin (PVL) genes. Medical records review and epidemiologic classification was performed by an investigator blinded to the results of the bacterial strain analysis. Episodes of bloodstream infection were independently classified as either community-associated or healthcare-associated infections, and bacterial isolates were independently classified as either CA-MRSA strains or healthcare-associated MRSA (HA-MRSA) strains, according to established definitions. A tertiary care Veterans Affairs Medical Center. Twenty-four (65%) of 37 MRSA isolates were SCCmec type IV, a genetic type characteristic of CA-MRSA strains; 22 of these 24 isolates belonged to the CA-MRSA clone USA300 and carried PVL genes. Thirteen (35%) of the 37 strains were SCCmec type II, of which 12 were USA100-ST5 and 12 lacked PVL genes. Thirty patients (81%) had healthcare-associated infections; 18 (60%) of these 30 were infected with isolates carrying markers of CA-MRSA strains. Of 7 patients with CA-MRSA infections, 6 were infected with isolates belonging to the USA300 clone. Patients with healthcare-associated bloodstream infections were as likely to be infected with a CA-MRSA strain as patients with a community-associated infection (P = .38). MRSA strains with molecular characteristics of CA-MRSA strains have emerged as an important cause of serious healthcare-associated infection in our hospital.
    Infection Control and Hospital Epidemiology 11/2006; 27(10):1051-6. · 4.02 Impact Factor
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    ABSTRACT: Background: Probiotics, viable organisms given by mouth to replenish bowel flora, are used as an adjunct to treat C. difficile colitis. Although not regulated by the FDA, these preparations are sold as dietary supplements; Lactobacillus (LB) and Saccharomyces are common ingredients. We compared the actual bacterial speciation and CFU to the label. Susceptibility to relevant antibiotics was studied. A randomized, blinded, placebo-controlled pilot study was begun using Lactobacillus GG. Methods: Probiotics were purchased: 7 from internet site; 7 from US pharmacy chains; 3 from health food stores; 1 from the manufacturer; 1 from VA pharmacy. Pills were ground anaerobically in 10 ml of prereduced PBS, diluted, streaked on chocolate agar and incubated at 35 C anaerobically for up to 96 hr. MICs of metronidazole (MTNZ), vancomycin (VNC), amoxicillin/clavulanic acid AmC) and gatifloxacin (G) were assayed for lactobacilli. In an IRB-approved pilot trial, during treatment with MTNZ, 10 patients with C. difficile colitis were randomized to receive 28 days of Lactobacillus GG (resistant to MTNZ) or placebo. Results: Viable organisms were recovered from 18 of 19 samples (95%). Proper speciation often showed a discrepancy between the stated and actual identification. CFUs were within 95% of the stated number in 13 of 19 (68%) brands. One strain of lactobacillus was susceptible to all 4 antibiotics studied, 1 was resistant to all, and the rest had a variable pattern of resistance. Ten patients were randomized to receive Lactobacillus GG in addition to MTNZ: 4 (40%) responded (2 with Lactobacillus and 2 with placebo); 6 (60%) failed therapy or relapsed (3 with Lactobacillus and 3 with placebo). Conclusion: Most probiotic preparations contain bacteria in counts listed on the label, although the identification is often incorrect. Lactobacilli are often susceptible to MTNZ, VNC and other antibiotics, which would limit their usefulness if administered concurrently with the antibiotic. A pilot trial with Lactobacillus GG added to MTNZ showed no benefit from the probiotic.
    Infectious Diseases Society of America 2006 Annual Meeting; 10/2006
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    ABSTRACT: The recent proliferation of community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) has led to a marked increase in the need for outpatient treatment of MRSA infections. Many oral agents active against MRSA have been available for years, and a paucity of literature compares them, leaving physicians with little guidance for choosing among them. The purpose of the present study was to compare the bactericidal effects of orally available antibiotics against MRSA and to determine whether there were differences in antimicrobial killing activity against CA-MRSA and hospital-acquired (HA) MRSA isolates. A total of 12 unique patient MRSA isolates were studied. Six strains were CA, carrying the staphylococcal chromosomal cassette (SCCmec) type IVa, while six were HA and carried SCCmec type II. Time-kill methods were used to study the bactericidal activity of the orally available antimicrobials linezolid, rifampicin, trimethoprim/sulfamethoxazole, clindamycin, minocycline, and moxifloxacin alone and in combination in vitro. Trimethoprim/sulfamethoxazole was rapidly bactericidal resulting in >2 log(10) cfu/mL decrease at 8 h and >3 log(10) cfu/mL decrease at 24 h in vitro. No antibiotic combination exhibited better killing than trimethoprim/sulfamethoxazole alone. Adding rifampicin to trimethoprim/sulfamethoxazole showed a trend towards antagonism in vitro. There were no differences in the bactericidal activity of any antimicrobial or antimicrobial combination against MRSA isolates carrying SCCmec type IVa versus those carrying SCCmec type II. Trimethoprim/sulfamethoxazole is rapidly bactericidal against MRSA in vitro when compared with most other orally available antimicrobials. No differences in bactericidal activity were detected when activities against CA-MRSA and HA-MRSA were compared.
    Journal of Antimicrobial Chemotherapy 09/2006; 58(3):680-3. · 5.34 Impact Factor

Publication Stats

5k Citations
705.05 Total Impact Points


  • 1989–2013
    • Baylor College of Medicine
      • • Section of Infectious Diseases
      • • Department of Medicine
      • • Veterans Affairs Medical Center
      Houston, TX, United States
    • University of Wisconsin, Madison
      • Department of Medical Microbiology and Immunology
      Madison, MS, United States
  • 2004–2007
    • Michael E. DeBakey VA Medical Center
      Houston, Texas, United States
  • 1992–2005
    • University of Texas Health Science Center at Houston
      • Medical School
      Houston, TX, United States
  • 2003
    • Emory University
      • School of Medicine
      Atlanta, GA, United States
  • 2001–2002
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 1995–2002
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
  • 1997
    • University of North Carolina at Chapel Hill
      • Division of Infectious Diseases
      Chapel Hill, NC, United States
  • 1996
    • University of Missouri - Kansas City
      Kansas City, Missouri, United States
  • 1994
    • Philadelphia University
      Philadelphia, Pennsylvania, United States
  • 1991
    • University of Houston
      • College of Pharmacy
      Houston, TX, United States