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Biomedical subjects

L A Mandell

Publications and source records attributed to L A Mandell.

At least 19 recordsLinked to original sources
PubMed2001

Antimicrobial safety and tolerability: differences and dilemmas.

The adverse drug reactions associated with antimicrobials have become a topic of major importance and concern in the last few years. Antimicrobial toxicity may take many forms, varying from mild, transient phenomena to dramatic, life-threatening events such as seizures or cardiac arrhythmias. We review the toxicity of antimicrobials in general and of the fluoroquinolones in particular and attempt to explain the adverse events by use of structure-adverse event relationships where possible. There are currently 5 main mechanisms that can be invoked to explain antimicrobial toxicity: direct effects, hypersensitivity, changes in microbial flora, drug interactions, and microbial lysis. The adverse drug reactions seen with fluoroquinolones are explained on the basis of these 5 mechanisms. The various organ systems affected by the fluoroquinolones are considered; then individual members of the fluoroquinolone class are reviewed. The unexpected and dramatic problems encountered with temafloxacin and trovafloxacin are discussed as well.

Anti-Infective Agents↗
PubMed2001

Interspecies recombination contributes minimally to fluoroquinolone resistance in Streptococcus pneumoniae.

Analysis of 71 ciprofloxacin-resistant (MIC > or = 4 microg/ml) Streptococcus pneumoniae clinical isolates revealed only 1 for which the quinolone resistance-determining regions of the parC, parE, and gyrB genes were genetically related to those of viridans group streptococci. Our findings support the occurrence of interspecies recombination of type II topoisomerase genes; however, its contribution to the emergence of quinolone resistance among pneumococci appears to have been minimal.

Amino Acid Sequence↗
PubMed2000

Fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae: contributions of type II topoisomerase mutations and efflux to levels of resistance.

We report on amino acid substitutions in the quinolone resistance-determining region of type II topisomerases and the prevalence of reserpine-inhibited efflux for 70 clinical isolates of S. pneumoniae for which the ciprofloxacin MIC is >/=4 microgram/ml and 28 isolates for which the ciprofloxacin MIC is </=2 microgram/ml. The amino acid substitutions in ParC conferring low-level resistance (MICs, 4 to 8 microgram/ml) included Phe, Tyr, and Ala for Ser-79; Asn, Ala, Gly, Tyr, and Val for Asp-83; Asn for Asp-78; and Pro for Ala-115. Isolates with intermediate-level (MICs, 16 to 32 microgram/ml) and high-level (MICs, 64 microgram/ml) resistance harbored substitutions of Phe and Tyr for Ser-79 or Asn and Ala for Asp-83 in ParC and an additional substitution in GyrA which included either Glu-85-Lys (Gly) or Ser-81-Phe (Tyr). Glu-85-Lys was found exclusively in isolates with high-level resistance. Efflux contributed primarily to low-level resistance in isolates with or without an amino acid substitution in ParC. The impact of amino acid substitutions in ParE was minimal, and no substitutions in GyrB were identified.

Amino Acid Substitution↗
PubMed2000

Comparative in vitro activities of ciprofloxacin, gemifloxacin, grepafloxacin, moxifloxacin, ofloxacin, sparfloxacin, trovafloxacin, and other antimicrobial agents against bloodstream isolates of gram-positive cocci.

The in vitro activity of gemifloxacin against 316 bloodstream isolates of staphylococci, pneumococci, and enterococci was compared with the activities of six fluoroquinolones and three other antimicrobial agents. Of the antimicrobial agents tested, gemifloxacin was the most potent against penicillin-intermediate and -resistant pneumococci, methicillin-susceptible and -resistant Staphylococcus epidermidis isolates, and coagulase-negative staphylococci.

Anti-Bacterial Agents↗
PubMed1999

Antibiotic therapy for community-acquired pneumonia.

This article takes a broad perspective of community-acquired pneumonia (CAP). The arguments and data that support or refute the current approaches to initial antimicrobial treatment of CAP as outlined in the American Thoracic Society and Infectious Disease Society of America documents are provided. The complex issues involved in the decision of how to properly treat CAP are addressed.

Anti-Bacterial Agents↗
PubMed1999

[The role of trovafloxacin in the treatment of nosocomial pneumonia].

In order to understand the role of trovafloxacin in the treatment of nosocomial pneumonia, the nature and characteristics of this infection have to be first reviewed. During the first part of this revision the principal aspects of the epidemiology are reviewed, some concepts which take part in the pathogenia of the illness and the immunology of these patients are analysed and the microbiological characteristics of nosocomial pneumonia are evaluated. In the second part of the revision the bacterial resistance to the main groups of antibiotics is considered, listing the different mechanisms used by the bacteria to develop this resistance. They are: production of enzymes which inactivate the antibiotic, access reduction of the drug to the target site, increase of the antibiotic efflux or changes in the target site. Current controversies concerning diagnostic methods and some controversial issues regarding this pathology are here discussed. Finally, the proposed guidelines for the treating hospital acquired pneumonia are revised as well as the role of special new antibiotics. In this sense special reference is made to trovafloxacin, listing its principal characteristics, as its broad spectrum of activity, its excellent pharmacokinetic properties, its availability in i.v. and oral formulations and its good tolerance, which makes trovafloxacin a very interesting option for treatment of hospital acquired pneumonia.

Anti-Infective Agents↗
PubMed1998

Community-acquired pneumonia in adults: guidelines for management. The Infectious Diseases Society of America.

This is part of the series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of community-acquired pneumonia. The targeted providers are internists and family practitioners. The targeted groups are immunocompetent adult patients. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy. Panel members and consultants are experts in adult infectious diseases. The guidelines are evidence based where possible. A standard ranking system is used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary and tables highlight the major recommendations. The guidelines will be listed on the IDSA home page at http://www.idsociety.org.

Adult↗
PubMed1998

Nosocomial pneumonia guidelines: an international perspective.

Hospital-acquired pneumonia is a serious illness with substantial morbidity and mortality. Management of this illness is challenging for the physician and a number of diverse issues must be considered when initiating therapy. Guidelines for the treatment of hospital-acquired pneumonia have been developed in Canada and the United States. A questionnaire sent to infectious disease physicians or clinical microbiologists in 29 countries showed that Australia, Sweden, and France had national guidelines in addition to Canada and the United States, while Hong Kong and France had single hospital-based guidelines. These guidelines are reviewed and some of the controversial issues relating to nosocomial pneumonia are discussed.

Canada↗
PubMed1996

Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: effect of augmented gram-positive activity on infectious morbidity. National Cancer Institute of Canada Clinical Trials Group.

OBJECTIVE: To determine whether augmented quinolone-based antibacterial prophylaxis in neutropenic patients with cancer reduces infections caused by gram-positive cocci and preserves the protective effect against aerobic gram-negative bacilli. DESIGN: Open, randomized, controlled, multicenter clinical trial. SETTING: Centers participating in the National Cancer Institute of Canada Clinical Trials Group. PATIENTS: 111 eligible and evaluable patients hospitalized for severe neutropenia (neutrophil count < 0.5 x 10(9)/L lasting at least 14 days) who were receiving cytotoxic therapy for acute leukemia or bone marrow autografting. INTERVENTION: One of three oral antibacterial prophylactic regimens (norfloxacin, 400 mg every 12 hours; ofloxacin, 400 mg every 12 hours; or ofloxacin, 400 mg, plus rifampin, 300 mg every 12 hours) beginning with cytotoxic therapy. MEASUREMENTS: Incidence and cause of suspected or proven infection. RESULTS: Microbiologically documented overall infection rates for norfloxacin, ofloxacin, and ofloxacin plus rifampin were 47%, 24%, and 9%, respectively (P < 0.001). Corresponding rates were 24%, 13%, and 3%, respectively for staphylococcal bacteremia (P = 0.03) and, 21%, 3%, and 3%, respectively for streptococcal bacteremia (P < 0.01). The pattern of bacteremia suggested that rifampin played a role in suppressing staphylococcal infection. Both ofloxacin alone and ofloxacin plus rifampin had a clinically significant antistreptococcal effect. Aerobic gram-negative rods were cleared from rectal surveillance cultures in all patients after a median of 5.5 days and caused infection in only one patient (0.9%). The reductions in the number of microbiologically documented infections among ofloxacin recipients and ofloxacin plus rifampin recipients were offset by concomitant increases in the number of unexplained fevers (24% of norfloxacin recipients, 53% of ofloxacin recipients, and 49% of ofloxacin plus rifampin recipients; P = 0.02). No statistically significant difference was found among the treatment arms with respect to the overall incidence of febrile neutropenic episodes as defined for this trial (79% for the norfloxacin group, 82% for the ofloxacin group, and 77% for the ofloxacin plus rifampin group). CONCLUSIONS: Quinolone-based antibacterial chemoprophylaxis protected patients from aerobic gram-negative bacillary infections. Augmentation of the gram-positive activity reduced the incidence of gram-positive infections but did not influence the overall incidence of febrile neutropenic episodes.

Adult↗
PubMed1996

Antimicrobial approaches to therapy for pneumonia.

Pneumonia remains a serious illness with significant associated morbidity and mortality. Parallelling our increased understanding of the etiology, epidemiology, and pathogenesis of pneumonia and the development of new antibiotics has been the frightening increase in the rate and extent of bacterial resistance. The prevalence of resistance has reached unprecedented levels in many countries, and we are facing the specter of infection by pathogens for which we have no effective treatment. To better understand some of the newer developments in this field, the discussion centers around the interactive triad of the host, pathogen, and drug. Pertinent developments relevant to each of these three areas are considered, along with a discussion of their clinical impact.

Anti-Bacterial Agents↗
PubMed1994

Antibiotics for pneumonia therapy.

When treating any infectious disease, a physician selects an antimicrobial based on the following considerations: the in vitro activity of the drug, its pharmacokinetic properties, the efficacy data based on properly designed and conducted clinical trials, and finally the adverse effects. In this article, all of these factors, with the exception of adverse effects, were discussed. It was neither my intent nor my purpose to deal with side effects or adverse drug reactions because these are well covered in standard texts or physician references such as the Physicians' Desk Reference and the American Hospital Formulary Service (United States) and the Compendium of Pharmaceuticals and Specialties (Canada).

Anti-Infective Agents↗