OBJECTIVES: We characterized distinctive features of a hypertransmissible carbapenem-resistant Klebsiella pneumoniae (CRKP) clone that emerged at Hadassah Hospital, Ein-Kerem, Jerusalem, Israel, in 2006. METHODS: Eleven CRKP isolated at Hadassah Hospital during 2005-09 were examined by antimicrobial susceptibility testing, PFGE and multilocus sequence typing (MLST). Plasmids were analysed by conjugation, restriction mapping, PCR and sequencing. RESULTS: Divergence from the national epidemic sequence type (ST) ST258 to ST512 was observed early on. Carbapenem resistance was conferred by bla(KPC-3) carried on a plasmid apparently closely related to pKpQIL, also from Israel. This clone also carried a 15 kb plasmid, designated pAAC154, that carries a Tn1331 derivative containing the aac(6′)-Ib gene. pAAC154 does not carry a bla(KPC) gene, but is similar to pS15, a plasmid from New York that carries bla(KPC-2). CONCLUSIONS: A single CRKP clone ST512 has spread efficiently in our region. In this clone, aac(6′)-Ib, common in CRKP strains, is carried on a different plasmid from bla(KPC-3).
PMID: 22287232 [PubMed - as supplied by publisher]
The combination of chloroquine and minocycline, a therapeutic option in cerebrospinal infection of Whipple’s disease refractory to treatment with ceftriaxone, meropenem and co-trimoxazole.
Differential alterations of the CD4 and CD8 T cell subsets in HIV-infected patients on highly active antiretroviral therapy with low CD4 T cell restoration.
J Antimicrob Chemother. 2012 Jan 27;
Authors: Méndez-Lagares G, García-Pergañeda A, Del Mar Del Pozo-Balado M, Genebat M, Ruiz-Mateos E, García García M, Muñoz-Fernández MA, Pacheco YM, Leal M
Abstract
OBJECTIVES: This study examined the homeostatic parameters possibly related to HIV-infected patients who, despite being under suppressive highly active antiretroviral therapy (HAART), show low-level CD4 T cell repopulation (LLR). METHODS: Twenty-one LLR individuals, 20 HIV-infected controls with satisfactory CD4 T cell repopulation (R) and 14 healthy subjects were studied. Markers related to activation, senescence and proliferation were analysed for both the CD4 and CD8 T cell subsets. Additionally, soluble CD14 (sCD14) and high-sensitivity C-reactive protein (hsCRP) were measured, and the CD34+ cells and the levels of interleukin-7 (IL-7) receptor were quantified. RESULTS: The frequency of naive CD4 T cells from LLR patients was significantly reduced, and these cells showed increased expression of markers for activation, senescence and proliferation as compared with naive CD4 T cells from R patients. Naive CD8 T cells were also reduced when compared with those from R patients, but did not exhibit an altered phenotype. Moreover, frequencies of effector memory T cells were higher in LLR than R patients. No differences between LLR and R patients were observed for sCD14 levels, CD34+ cells and the IL-7 receptor, although LLR patients showed a tendency toward increased levels of hsCRP >2 μg/mL. CONCLUSIONS: Patients with low CD4 T cell restoration under suppressive HAART show significant alterations in T cell homeostasis that do not appear to be related to a reduction in haematopoietic progenitors. sCD14 levels were not specifically altered in these patients. Our results agree with our previously proposed model of premature immunosenescence in LLR patients and further describe homeostatic features associated with poor CD4 recovery.
PMID: 22287235 [PubMed - as supplied by publisher]
Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs).
BACKGROUND: BC-3781 is an investigational semi-synthetic pleuromutilin antibiotic, which recently finished a clinical Phase 2 trial in acute bacterial skin and skin structure infections. BC-3781 binds to the 50S ribosomal subunit and cross-resistance with other antimicrobial classes is uncommon. We evaluated the activity of BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs). METHODS: BC-3781 and comparator agents were susceptibility tested against Streptococcus pneumoniae (157 isolates; 33% penicillin resistant), Haemophilus influenzae (102; 50% β-lactamase producers), Moraxella catarrhalis (50) and Legionella pneumophila (30) by broth microdilution and the agar dilution method. Mycoplasma pneumoniae (50 strains) was tested by broth microdilution, while Chlamydophila pneumoniae (50 strains) MIC values were determined using HEp-2 cells. RESULTS: Against S. pneumoniae (MIC(50/90) 0.12/0.25 mg/L) BC-3781 was 16- and 8-fold more active than azithromycin (MIC(50/90) 2/>16 mg/L) and levofloxacin (MIC(50/90) 1/1 mg/L), respectively, and its activity was not adversely affected by resistance to penicillin. S. pneumoniae showed high resistance rates to azithromycin (50.3%) and clindamycin (31.2%), all being inhibited by BC-3781 at concentrations ≤0.5 mg/L. H. influenzae and M. catarrhalis exhibited low BC-3781 MIC values independent of β-lactamase production. BC-3781 activity against L. pneumophila (MIC(50/90) 0.06/0.5 mg/L) was similar to that of erythromycin, but lower than that of azithromycin. BC-3781 also showed potent activity against M. pneumoniae and C. pneumoniae, with MIC(50/90) of 0.006/0.006 and 0.02/0.04 mg/L, respectively. CONCLUSIONS: BC-3781 was very active against organisms commonly associated with CARTIs and its activity was not negatively influenced by resistance to other antimicrobials.
PMID: 22287234 [PubMed - as supplied by publisher]
Spread of the epidemic European fusidic acid-resistant impetigo clone (EEFIC) in general practice patients in the south of The Netherlands.
J Antimicrob Chemother. 2012 Feb 2;
Authors: Rijnders MI, Wolffs PF, Hopstaken RM, den Heyer M, Bruggeman CA, Stobberingh EE
Abstract
OBJECTIVES: We evaluated the susceptibility to fusidic acid, mupirocin and retapamulin of Staphylococcus aureus isolated from nasal and wound swabs. METHODS: The susceptibility to the three agents of S. aureus isolated from general patients in the south of The Netherlands with a skin or soft tissue infection was determined between January 2007 and December 2008. Fusidic acid-resistant isolates were tested for the presence of fusidic acid-resistant genes and compared with the epidemic European fusidic acid-resistant impetigo clone (EEFIC). RESULTS: Fusidic acid resistance was found in 23% of the nasal and 35% of the wound isolates, the majority (∼90%) being fusB positive. Most of the isolates belonged to spa type t171 and were isolated from younger patients. One isolate was retapamulin resistant (MIC 8 mg/L) and two were mupirocin resistant. CONCLUSIONS: The EEFIC clone was relatively highly prevalent among the isolated S. aureus. The usefulness of fusidic acid as first-line agent for the treatment of impetigo is questionable. As mupirocin is used in The Netherlands for eradication of methicillin-resistant S. aureus, it is not an alternative; retapamulin might be useful, but further in vivo studies are warranted.
PMID: 22290345 [PubMed - as supplied by publisher]
Mycobacterium abscessus: a new antibiotic nightmare.
J Antimicrob Chemother. 2012 Jan 30;
Authors: Nessar R, Cambau E, Reyrat JM, Murray A, Gicquel B
Abstract
The intrinsic and acquired resistance of Mycobacterium abscessus to commonly used antibiotics limits the chemotherapeutic options for infections caused by these mycobacteria. Intrinsic resistance is attributed to a combination of the permeability barrier of the complex multilayer cell envelope, drug export systems, antibiotic targets with low affinity and enzymes that neutralize antibiotics in the cytoplasm. To date, acquired resistance has only been observed for aminoglycosides and macrolides, which is conferred by mutations affecting the genes encoding the antibiotic targets (rrs and rrl, respectively). Here we summarize previous and recent findings on the resistance of M. abscessus to antibiotics in light of what has been discovered for other mycobacteria. Since we can now distinguish three groups of strains belonging to M. abscessus (M. abscessus sensu stricto, Mycobacterium massiliense and Mycobacterium bolletii), studies on antibiotic susceptibility and resistance should be considered according to this new classification. This review raises the profile of this important pathogen and highlights the work needed to decipher the molecular events responsible for its extensive chemotherapeutic resistance.
PMID: 22290346 [PubMed - as supplied by publisher]
In vitro activity of the siderophore monosulfactam BAL30072 against meropenem-non-susceptible Acinetobacter baumannii.
J Antimicrob Chemother. 2012 Feb 1;
Authors: Higgins PG, Stefanik D, Page MG, Hackel M, Seifert H
Abstract
OBJECTIVES: The activity of BAL30072 was compared with that of anti-Acinetobacter reference drugs against meropenem-non-susceptible Acinetobacter baumannii isolates associated with up-regulation of the intrinsic OXA-51-like enzyme or an acquired OXA. METHODS: Antimicrobial susceptibility testing was investigated by broth microdilution of 310 non-duplicate, meropenem-non-susceptible A. baumannii isolates to BAL30072, amikacin ampicillin/sulbactam, aztreonam, cefepime, colistin, imipenem, levofloxacin, meropenem, rifampicin, tigecycline and tobramycin. RESULTS: BAL30072 showed greater activity than the β-lactam comparators, levofloxacin, amikacin, tobramycin and rifampicin. The activity of BAL30072 was comparable to that of tigecycline, with an MIC(50) of 2 mg/L. Elevated BAL30072 MICs were found, but there was no correlation with elevated MICs of the other antimicrobials. CONCLUSIONS: BAL30072 is a promising new agent with good activity against carbapenem-non-susceptible A. baumannii.
PMID: 22294643 [PubMed - as supplied by publisher]
Achieving a cure for HIV infection: do we have reasons to be optimistic?
J Antimicrob Chemother. 2012 Feb 1;
Authors: Le Douce V, Janossy A, Hallay H, Ali S, Riclet R, Rohr O, Schwartz C
Abstract
The introduction of highly active antiretroviral therapy (HAART) in 1996 has transformed a lethal disease to a chronic pathology with a dramatic decrease in mortality and morbidity of AIDS-related symptoms in infected patients. However, HAART has not allowed the cure of HIV infection, the main obstacle to HIV eradication being the existence of quiescent reservoirs. Several other problems have been encountered with HAART (such as side effects, adherence to medication, emergence of resistance and cost of treatment), and these motivate the search for new ways to treat these patients. Recent advances hold promise for the ultimate cure of HIV infection, which is the topic of this review. Besides these new strategies aiming to eliminate the virus, efforts must be made to improve current HAART. We believe that the cure of HIV infection will not be attained in the short term and that a strategy based on purging the reservoirs has to be associated with an aggressive HAART strategy.
PMID: 22294645 [PubMed - as supplied by publisher]
Impact of IL28B gene polymorphisms on interferon-λ3 plasma levels during pegylated interferon-α/ribavirin therapy for chronic hepatitis C in patients coinfected with HIV.
J Antimicrob Chemother. 2012 Feb 1;
Authors: Rallón NI, Soriano V, Naggie S, Restrepo C, McHutchison J, Vispo E, Benito JM
Abstract
OBJECTIVES: The mechanism explaining the strong association between IL28B rs12979860 polymorphisms and treatment outcome in chronic hepatitis C remains unclear. We explore whether IL28B protein [interferon (IFN)-λ3] plasma levels may vary according to IL28B genotype and/or following pegylated IFN-α/ribavirin therapy. PATIENTS AND METHODS: A total of 112 HIV/hepatitis C virus (HCV)-coinfected patients who completed a course of pegylated IFN-α/ribavirin therapy were examined. Sustained virological response (SVR) was achieved by 56% of patients. IL28B rs12979860 alleles were genotyped using the 5′ nuclease assay with specific TaqMan probes. A specific enzyme immunoassay was used to measure IFN-λ3 plasma levels before initiating anti-HCV therapy and at week 4 of treatment. RESULTS: No significant differences between CC and non-CC IL28B carriers were found at baseline, either in the proportion of patients with detectable IFN-λ3 plasma levels or in their median values. In contrast, median IFN-λ3 plasma levels at week 4 of therapy significantly increased with respect to baseline in CC carriers [34.3 (16.7-56.3) versus 15.6 (15.6-30.3) pg/mL, respectively; P < 0.0001], but not in CT/TT carriers. Unexpectedly, increases in IFN-λ3 at week 4 of therapy did not predict SVR. CONCLUSIONS: The exogenous administration of IFN-α may induce IFN-λ3 release in IL28B CC carriers, but not in CT/TT carriers. However, this finding does not account for the link between IL28B polymorphisms and treatment outcome.
PMID: 22294646 [PubMed - as supplied by publisher]
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