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K P Klugman

Publications and source records attributed to K P Klugman.

At least 19 recordsLinked to original sources
PubMed2007

Clarithromycin alone and in combination with ceftriaxone inhibits the production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of Streptococcus pneumoniae.

OBJECTIVES: To investigate the effects of clarithromycin (0.01-0.5 mg/L) alone or in combination with ceftriaxone (0.1 and 0.25 mg/L) on pneumolysin production by both macrolide-susceptible and -resistant [2 erm(B) positive and 2 mef(A) positive] strains of Streptococcus pneumoniae. METHODS: The bacteria were cultured for 6 h at 37 degrees C/5% CO(2) in tryptone soy broth, washed, enumerated and resuspended to 0.5-3 x 10(8) cfu/mL in tissue culture medium, RPMI 1640. After 16 h of incubation at 37 degrees C / 5% CO(2), pneumolysin was assayed in the bacteria-free supernatants, as well as in lysates, using a functional assay based on the influx of calcium into human neutrophils. RESULTS: Exposure of not only macrolide-susceptible strains, but also the macrolide-resistant strains, of S. pneumoniae to sub-MICs of clarithromycin resulted in dose-related inhibition of the pneumolysin production, whereas production of the toxin was unaffected by ceftriaxone. CONCLUSIONS: These observations demonstrate that even in the setting of macrolide resistance the production of pneumolysin, a key virulence factor of the pneumococcus, is attenuated by exposure of this microbial pathogen to clarithromycin.

Anti-Bacterial Agents↗
PubMed2006

Fluoroquinolone resistance in invasive Streptococcus pyogenes isolates due to spontaneous mutation and horizontal gene transfer.

Fluoroquinolone resistance in Streptococcus pyogenes has been described only anecdotally. In this study we describe two invasive ciprofloxacin-resistant S. pyogenes isolates (ciprofloxacin MICs, 8 mg/liter), one of which shows evidence of interspecies recombination. The quinolone resistance-determining regions of gyrA and parC were sequenced. In both isolates, there was no evidence for an efflux pump and no mutation in gyrA. Both isolates had an S79F mutation in parC that is known to confer fluoroquinolone resistance. In addition, a D91N mutation in parC, which is not related to fluoroquinolone resistance but is a feature of the parC sequence of Streptococcus dysgalactiae, was found in one isolate. The parC nucleotide sequence of that isolate showed greater diversity than that of S. pyogenes. A GenBank search and phylogenetic analysis suggest that this isolate acquired resistance by horizontal gene transfer from S. dysgalactiae. Statistical testing for recombination confirmed interspecies recombination of a 90-bp sequence containing the S79F mutation from S. dysgalactiae. For the other isolate, we could confirm that it acquired resistance by spontaneous mutation by identifying the susceptible ancestor in an outbreak setting.

Adult↗
PubMed2005

Ciprofloxacin treatment failure in a patient with resistant Streptococcus pneumoniae infection following prior ciprofloxacin therapy.

Reported here is the case of a patient with underlying chronic obstructive pulmonary disease (COPD) in whom ciprofloxacin treatment of a lower respiratory tract infection failed subsequent to ciprofloxacin treatment of an exacerbation of COPD several weeks earlier. During the second course of ciprofloxacin therapy, the patient's condition continued to deteriorate, and she was admitted to the intensive care unit. Bilateral pneumonia was diagnosed. Streptococcus pneumoniae, serotype 11A, resistant to ciprofloxacin was isolated from the sputum. Sequencing revealed a S79F mutation in parC and there was evidence of an efflux pump. The patient improved rapidly after administration of azithromycin and ampicillin/sulbactam. This report of treatment failure due to ciprofloxacin-resistant Streptococcus pneumoniae shows that fluoroquinolones should be avoided when treating patients who have recently received this class of antibiotics.

Aged↗
PubMed2004

Community-acquired pneumonia: new management strategies for evolving pathogens and antimicrobial susceptibilities.

Community-acquired pneumonia (CAP) is still one of the leading causes of mortality and morbidity. The most common bacterial cause of CAP is Streptococcus pneumoniae. The increase in antimicrobial resistance has raised concerns about the efficacy of available therapies, and a call for the reassessment of both existing and newer therapeutic agents. Although microbiological breakpoints are useful for monitoring the emergence of resistance, the current National Committee for Clinical Laboratory Standards (NCCLS) guidelines make no distinction between clinical and microbiological breakpoints. Recent changes in NCCLS breakpoints for extended spectrum cephalosporins have provided a more meaningful approach to susceptibility testing and to consideration of the site of infection. Further controversy surrounds the clinical guidelines relating to CAP in terms of which antimicrobial agents should be given empirically to which types of patients. Within this review, the role of monotherapy versus the need for combination antimicrobial therapy, which often includes a macrolide and an extended spectrum cephalosporin such as ceftriaxone, is discussed. This review also discusses the various aspects of antimicrobial susceptibilities of S. pneumoniae, the drivers and influences of increasing resistance, the clinical relevance of this resistance and possible therapeutic options in the face of changing susceptibilities and mixed bacterial aetiologies. New guidelines from the IDSA attempt to embrace these changes.

Anti-Bacterial Agents↗
PubMed2004

Future trends in antimicrobial chemotherapy: expert opinion on the 43rd ICAAC.

The current document bestows an expert synopsis of key new information presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in 2003. Data is presented on the socio-political aspects of and policies on antimicrobial prescribing, novel mechanisms of resistance in Streptococcus pneumoniae, and current epidemiological trends in global resistance. Novel information on new (and existing) antimicrobial agents--new penicillins, cephalosporins, monobactams and oxipenem inhibitors, ketolides, glycopeptides, fluoroquinolones (and hybrids), peptides, daptomycin, aminomethylcyclines, glycylcyclines, and newer formulations of agents such as amoxycillin-clavulanate--provides renewed hope that resistant pathogens can be controlled through use of more potent agents. Improved strategies for the use of existing antimicrobial agents, such as the use of high-dose regimens, short-course therapy, also may delay or reduce the development of resistance and preserve the value of our antibiotic armamentarium.

Anti-Bacterial Agents↗
PubMed2002

Severe lower respiratory tract infections associated with human parainfluenza viruses 1-3 in children infected and noninfected with HIV type 1.

The aim of this study was to compare the clinical course of severe lower respiratory tract infections associated with human parainfluenza virus types 1-3 (HPIV 1-3) in hospitalised children infected with the human immunodeficiency virus type 1 (HIV-1) versus that in hospitalised children not infected with HIV-1. Children were enrolled prospectively as part of a broader study that evaluated the aetiology of lower respiratory tract infections in HIV-1-infected and -noninfected children from March 1997 through March 1999. HPIV types 1-3 were isolated from nasopharyngeal aspirate samples that were analysed using immunofluorescein monoclonal antibody assays. Thirty percent (24 of 80) of the children from whom HPIV was isolated were infected with HIV-1. Sixty-six percent (47 of 62) and 22% (14 of 62) of the HPIV isolates that were typed were subtypes 3 and 1, respectively. The clinical presentation of severe lower respiratory tract infection was similar in both HIV-1-infected and -noninfected children, except that the former were less likely to have wheezing (4.2% vs. 28.6%, P=0.01). Furthermore, the duration of hospitalisation was longer in HIV-1-infected children than in HIV-1-noninfected children (median 11.5 days [range 1-15 days] vs. median 7.5 days [range 1-22 days]; P=0.02), and mortality was higher (5 of 24 [20.8%] infected children vs. 0 of 56 noninfected children; P=0.001). Importantly, four of five (80%) of the HIV-1-infected children who died had other concurrent illnesses or predisposing factors for severe HPIV-associated disease. HPIV-associated lower respiratory tract infection causes greater morbidity and mortality in HIV-1-infected children than in HIV-1-noninfected children; however, this may be due to other concurrent illnesses in HIV-1-infected children.

Child, Preschool↗
PubMed2002

The successful clone: the vector of dissemination of resistance in Streptococcus pneumoniae.

A small number of pneumococcal clones dominate the population of antibiotic-resistant pneumococci. The emergence of fluoroquinolone resistance in these clones predicts the dissemination of fluoroquinolone resistance in countries where the clones are present and community use of fluoroquinolones for respiratory infections is common. The molecular basis of resistance to a number of classes of antimicrobials can be used to predict the likelihood of dissemination of the resistance genes.

Animals↗
PubMed2002

Bacteriological evidence of antibiotic failure in pneumococcal lower respiratory tract infections.

The global pandemic of antimicrobial resistance, particularly in the pneumococcus, has had a major impact on the management of community-acquired pneumonia. A number of prospective and retrospective studies have analysed the impact of penicillin resistance on clinical outcome in pneumonia. Pharmacodynamic principles predicting success when the antibiotic dose exceeds the minimum inhibitory concentration (MIC) for 40-50% of the dosing interval have proved remarkably accurate. There is no evidence of bacteriological failure of penicillins active against resistant strains. There is a single report of the failure of the less active agent, ticarcillin. High dose oral and intravenous amoxicillin should treat strains with MICs < or = 4 microg x mL(-1), as should high doses of intravenous penicillin, ceftriaxone and cefotaxime. Strains of pneumococci resistant to these agents at an MIC > or = 8 microg x mL(-1) are rare at the present time. Most other cephalosporins are less active and should not be used empirically for drug-resistant Streptococcus pneumoniae. Bacteriological failures of cefazolin, cefuroxime and ceftazidime have been reported. There is increasing evidence of bacteriologically confirmed macrolide failure of pneumonia therapy at MICs > or = 4 microg x mL(-1). The molecular basis of the resistance is irrelevant if the MIC is in that range or higher. Double mutants in the parC and gyrA genes lead to fluoroquinolone resistance that has been found to cause bacteriological failure of the fluoroquinolones, particularly levofloxacin and ciprofloxacin, in the management of pneumonia and exacerbations of chronic bronchitis. Two mutations in these genes can greatly increase the MICs of all the marketed fluoroquinolones, and raise the prospect of failure of therapy even with the more active ones. However, demonstration of bacteriological failure of gatifloxacin or moxifloxicin has not yet been reported. High dose, active beta-lactams or fluoroquinolones with enhanced activity against Gram positive pathogens remain the drugs of choice for the management of community-acquired pneumonia caused by the drug-resistant pneumococcus.

Anti-Bacterial Agents↗
PubMed2001

Impact of human immunodeficiency virus type 1 infection on the epidemiology and outcome of bacterial meningitis in South African children.

OBJECTIVE: To define the impact that the human immunodeficiency virus type 1 (HIV-1) epidemic has had on the burden and outcome of bacterial meningitis in an area with a high prevalence of pediatric HIV-1 infection. METHODS: Children less than 12 years of age with proven or suspected bacterial meningitis were enrolled in this study between March 1997 and February 1999, and their hospital records were retrospectively reviewed for clinical data. RESULTS: Sixty-two (42.2%) of the 147 children tested for HIV-1 infection were infected. Streptococcus pneumoniae (Pnc) exceeded Haemophilus influenzae type b (Hib) as the most important cause of meningitis in HIV-1-infected (74.2% vs. 12.9%, respectively) compared with uninfected children (29.4% vs. 42.3%, respectively, P less than 10(-5)). The estimated relative risk of Pnc meningitis was greater in HIV-1-infected than in uninfected children under 2 years of age (relative risk [RR] = 40.4; 95% confidence intervals [CI] = 17.7-92.2). Overall, HIV-1-infected children had a higher rate of mortality than uninfected children (30.6% vs. 11.8%, respectively, P = 0.01), and in particular, HIV-1-infected children with Pnc meningitis (60.8% vs. 36.0%, respectively, P = 0.04) had a poorer outcome. CONCLUSIONS: Streptococcus pneumoniae has exceeded Hib as the most important pathogen causing bacterial meningitis in HIV-1-infected compared with uninfected children. Effective vaccination against Hib and Pnc should be evaluated to reduce the overall burden of bacterial meningitis in HIV-1-infected children.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Efficacy of pneumococcal conjugate vaccines and their effect on carriage and antimicrobial resistance.

Pneumococcal conjugate vaccines have shown a high degree of success in preventing pneumococcal bacteraemia in children. They also reduce the acquisition of carriage of vaccine serotypes in the nasopharynx, and reduce otitis media caused by those serotypes. Non-vaccine serotypes, which can colonise vaccinated infants, are associated with otitis media in these children and lower the overall effectiveness of the vaccine to this disorder. Longer term studies, however, could show that immunised children develop immunity to a broad range of pneumococcal serotypes at a younger age than non-immunised children. Preliminary data suggest that these vaccines could reduce the burden of radiologically confirmed pneumonia. Pneumococcal conjugate vaccines interrupt the transmission of antibiotic-resistant pneumococci and thus decrease the burden of antibiotic resistance in immunised children and in their contacts. Studies are underway to assess conjugate vaccine efficacy against invasive disease, pneumonia, and all-cause mortality in developing countries, and to assess the potential use of these vaccines in adults.

Carrier State↗
PubMed2001

Prevalence of serotypes and molecular epidemiology of Streptococcus pneumoniae strains isolated from children in Beijing, China: identification of two novel multiply-resistant clones.

Three-hundred and seventy-six strains of Streptococcus pneumoniae isolated from clinical specimens and nasopharyngeal swabs from children at daycare centers and hospitals in Beijing China, between January 1997 and March 1998, were serotyped. Twenty-seven different serotypes were identified. The most prevalent serotypes in the carriage isolates were 6A, 19F, 23F, and 15 and were found in 66.8% of cases. Serotype data indicate that 51.8% of carrier strains would be included in the 11-valent conjugate vaccine formulation, while inclusion of vaccine-related serotypes, increased the potential vaccine coverage to 79.4%. Serotypes 7, 6B, 23F, 19F, 15, and 3 accounted for 62% of clinical strains, with 70% vaccine-related serotypes. DNA fingerprinting of 47 penicillin resistant and 71 penicillin-susceptible/macrolide-resistant strains by BOX polymerase chain reaction (PCR), pulsed-field gel electrophoresis (PFGE), and penicillin binding protein (PBP)-fingerprinting identified two novel clones: one a serotype 23F multiresistant clone resistant to penicillin, tetracycline, erythromycin, clindamycin, and variably resistant to chloramphenicol and trimethoprim-sulphamethoxazole; and the second a multiresistant penicillin-susceptible, macrolide-resistant serotype 6A clone, highly resistant also to tetracycline, clindamycin, and trimethoprim-sulphamethoxazole. The macrolide resistance determinant in 89% of erythromycin-resistant strains tested (penicillin-susceptible and penicillin-resistant) was the erm gene, both the erm and mef genes were simultaneously found in 6%, and mef alone in 3.4%. The data demonstrates that macrolide resistant strains in China include clonal strains and strains with dual mef and erm resistance determinants.

Anti-Bacterial Agents↗
PubMed2001

Evidence to support the rationale that bacterial eradication in respiratory tract infection is an important aim of antimicrobial therapy.

Clinical outcome is dependent upon antibiotic-mediated bacterial eradication in a number of infections. However, in respiratory tract infections, the need for bacterial eradication has been controversial. Clinical data are now available that support the need for active bacterial eradication in otitis media. This may also be the case for other respiratory tract infections. An increase in antimicrobial resistance reduces the probability of achieving eradication. Conversely, failure to eradicate bacteria may promote the emergence and dissemination of antimicrobial-resistant clones. Pharmacokinetic/pharmacodynamic parameters can be used to predict the bacteriological efficacy of antimicrobial therapy. In conclusion, the aim of antimicrobial therapy in respiratory tract infections should be the eradication of the infecting organism.

Anti-Bacterial Agents↗
PubMed2001

Streptococcus pneumoniae respiratory tract infections.

This review describes recent contributions to our understanding of pneumococcal pneumonia. Two genes have been described that encode enzymes involved with the biosynthesis of muropeptides. These enzymes may be novel antibiotic targets. The clinical impact of increasing antibiotic resistance on the treatment of pneumonia is the particular focus of the review. As resistant strains are more commonly associated with severe infections in patients with underlying disease, the interpretation of an association of resistance with poor clinical outcome is complicated.

Aged↗
PubMed2001

Differing manifestations of respiratory syncytial virus-associated severe lower respiratory tract infections in human immunodeficiency virus type 1-infected and uninfected children.

BACKGROUND: Respiratory syncytial virus (RSV) causes increased morbidity and mortality in immunocompromised children. The outcome of RSV-associated lower respiratory tract infections (LRTI) in HIV-infected children, is less well described. METHODS: Children from a prospective study evaluating the etiology of

Age Factors↗
PubMed2001

Serotype 19f multiresistant pneumococcal clone harboring two erythromycin resistance determinants (erm(B) and mef(A)) in South Africa.

One hundred eighteen erythromycin-resistant Streptococcus pneumoniae (ERSP) strains (MICs of > or = 0.5 microg/ml) from five laboratories serving the private sector in South Africa were analyzed for the genes encoding resistance to macrolides. Sixty-seven ERSP strains (56.8%) contained the erm(B) gene, and 15 isolates (12.7%) contained the mef(A) gene. Thirty-six isolates (30.5%) harbored both the erm(B) and mef(A) genes and were highly resistant to erythromycin and clindamycin. DNA fingerprinting by BOX-PCR and pulsed-field gel electrophoresis identified 83% of these strains as belonging to a single multiresistant serotype 19F clone.

Anti-Bacterial Agents↗