Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters

<p>Abstract</p> <p>Background</p> <p>Diagnosis of primary HIV infection (PHI) has important clinical and public health implications. HAART initiation at this stage remains controversial.</p> <p>Methods</p> <p>Our objective was to identify predictors of disease progression among Argentinean seroconverters during the first year of infection, within a multicentre registry of PHI-patients diagnosed between 1997 and 2008. Cox regression was used to analyze predictors of progression (LT-CD4 < 350 cells/mm³, B, C events or death) at 12 months among untreated patients.</p> <p>Results</p> <p>Among 134 subjects, 74% presented with acute retroviral syndrome (ARS). Seven opportunistic infections (one death), nine B events, and 10 non-AIDS defining serious events were observed. Among the 92 untreated patients, 24 (26%) progressed at 12 months versus three (7%) in the treated group (p = 0.01). The 12-month progression rate among untreated patients with ARS was 34% (95% CI 22.5-46.3) versus 13% (95% CI 1.1-24.7) in asymptomatic patients (p = 0.04). In univariate analysis, ARS, baseline LT-CD4 < 350 cells/mm³, and baseline and six-month viral load (VL) > 100,000 copies/mL were associated with progression. In multivariate analysis, only ARS and baseline VL > 100,000 copies/mL remained independently associated; HR: 8.44 (95% CI 0.97-73.42) and 9.44 (95% CI 1.38-64.68), respectively.</p> <p>Conclusions</p> <p>In Argentina, PHI is associated with significant morbidity. HAART should be considered in PHI patients with ARS and high baseline VL to prevent disease progression.</p

Evidence for the Active Role of a Novel Nuclease from Helicobacter pylori in the Horizontal Transfer of Genetic Information

Helicobacter pylori is a gram-negative bacterium that colonizes the human stomach, causes gastritis, and is associated with ulcers and gastric cancer. H. pylori is naturally competent for transformation. Natural genetic transformation is believed to be essential for the genetic plasticity observed in this species. While the relevance of horizontal gene transfer in H. pylori adaptiveness and antibiotic resistance is well documented, the DNA transformation machinery components are barely known. No enzymatic activity associated with the transformation process has been determined experimentally and described. We isolated, microsequenced, and cloned a major DNA nuclease from H. pylori. This protein, encoded by the open reading frame hp0323, was expressed in Escherichia coli. The purified protein, NucT, has a cation-independent thermostable nuclease activity that preferentially cleaves single-stranded DNA. NucT is associated with the membrane. NucT-deficient H. pylori strains are one or more orders of magnitude less efficient than the parental strain for transformation with either chromosomal or self-replicating plasmid DNA. To the best of our knowledge, NucT is the first nuclease identified in a gram-negative natural transformation system, and its existence suggests that there is a mechanism of DNA processing and uptake similar to the mechanisms in well-studied gram-positive systems

Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum beta-lactamases in a Klebsiella pneumoniae clinical strain isolated in Argentina

Fil: Melano, Roberto. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Antimicrobianos; Argentina.Fil: Corso, Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Antimicrobianos; Argentina.Fil: Petroni, Alejandro. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Antimicrobianos; Argentina.Fil: Centrón, Daniela. Universidad de Buenos Aires. Departamento de Microbiología; Argentina.Fil: Orman, Betina. Universidad de Buenos Aires. Departamento de Microbiología; Argentina.Fil: Pereyra, Adriana. Hospital Gobernador Centeno. Servicio de Bacteriología; Argentina.Fil: Moreno, Noemí. Hospital Gobernador Centeno. Servicio de Bacteriología; Argentina.Fil: Galas, Marcelo F. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Antimicrobianos; Argentina.Klebsiella pneumoniae M1803, isolated from a paediatric patient with chronic urinary infection, presented nine antimicrobial resistance mechanisms harboured on two conjugative megaplasmids, in addition to the chromosomally mediated SHV-1 beta-lactamase. These nine antimicrobial resistance mechanisms comprised two extended-spectrum beta-lactamases (ESBLs) (PER-2 and CTX-M-2), TEM-1-like, OXA-9-like, AAC(3)-IIa, AAC(6')-Ib, ANT(3")-Ia and resistance determinants to tetracycline and chloramphenicol. During fluoroquinolone treatment, a variant derived from M1803 (named M1826) was selected, with an overall increase of MICs, in particular of cefoxitin and carbapenems. No enzymic activity against these latter drugs was found. Mutations in the region analogous to the quinolone resistance-determining region were not found. Strain M1826 was deficient in OmpK35/36 expression, which produced the decrease in the susceptibility to cefoxitin, carbapenems and fluoroquinolones. The blaCTX-M-2 gene was located in an unusual class 1 integron, which includes Orf513, as occurred in the recently described In35. In addition, Tn3 and Tn1331 were detected in both K. pneumoniae isolates. This is the first report of in vivo selection of an OmpK35/36 deficiency in a K. pneumoniae strain that produced a novel combination of two ESBLs (CTX-M-2 and PER-2) during fluoroquinolone treatment in a paediatric patient with chronic urinary infection

Multiple antibiotic-resistance mechanisms including a novel combination of extended-spectrum beta-lactamases in a Klebsiella pneumoniae clinical strain isolated in Argentina

Fil: Melano, Roberto. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Antimicrobianos; Argentina.Fil: Corso, Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Antimicrobianos; Argentina.Fil: Petroni, Alejandro. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Antimicrobianos; Argentina.Fil: Centrón, Daniela. Universidad de Buenos Aires. Departamento de Microbiología; Argentina.Fil: Orman, Betina. Universidad de Buenos Aires. Departamento de Microbiología; Argentina.Fil: Pereyra, Adriana. Hospital Gobernador Centeno. Servicio de Bacteriología; Argentina.Fil: Moreno, Noemí. Hospital Gobernador Centeno. Servicio de Bacteriología; Argentina.Fil: Galas, Marcelo F. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Bacteriología. Servicio de Antimicrobianos; Argentina.Klebsiella pneumoniae M1803, isolated from a paediatric patient with chronic urinary infection, presented nine antimicrobial resistance mechanisms harboured on two conjugative megaplasmids, in addition to the chromosomally mediated SHV-1 beta-lactamase. These nine antimicrobial resistance mechanisms comprised two extended-spectrum beta-lactamases (ESBLs) (PER-2 and CTX-M-2), TEM-1-like, OXA-9-like, AAC(3)-IIa, AAC(6')-Ib, ANT(3")-Ia and resistance determinants to tetracycline and chloramphenicol. During fluoroquinolone treatment, a variant derived from M1803 (named M1826) was selected, with an overall increase of MICs, in particular of cefoxitin and carbapenems. No enzymic activity against these latter drugs was found. Mutations in the region analogous to the quinolone resistance-determining region were not found. Strain M1826 was deficient in OmpK35/36 expression, which produced the decrease in the susceptibility to cefoxitin, carbapenems and fluoroquinolones. The blaCTX-M-2 gene was located in an unusual class 1 integron, which includes Orf513, as occurred in the recently described In35. In addition, Tn3 and Tn1331 were detected in both K. pneumoniae isolates. This is the first report of in vivo selection of an OmpK35/36 deficiency in a K. pneumoniae strain that produced a novel combination of two ESBLs (CTX-M-2 and PER-2) during fluoroquinolone treatment in a paediatric patient with chronic urinary infection

Vibrio cholerae InV117, a Class 1 Integron Harboring aac(6′)-Ib and bla(CTX-M-2), Is Linked to Transposition Genes

A ca. 150-kbp Vibrio cholerae O1 biotype El Tor plasmid includes bla(CTX-M-2) and a variant of aac(6′)-Ib within InV117, an orf513-bearing class 1 integron. InV117 is linked to a tnp1696 module in which IRl carries an insertion of IS4321R. The complete structure could be a potential mobile element

Vibrio cholerae InV117, a class 1 integron harboring aac(6')-Ib and blaCTX-M-2, is linked to transposition genes

Fil: Soler Bistué, Alfonso J. C. Fundación Instituto Leloir; Argentina.Fil: Martín, Fernando A. Fundación Instituto Leloir; Argentina.Fil: Petroni, Alejandro. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Servicio de Antimicrobianos; Argentina.Fil: Faccone, Diego. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Servicio de Antimicrobianos; Argentina.Fil: Galas, Marcelo F. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Servicio de Antimicrobianos; Argentina.Fil: Tolmasky, Marcelo E. California State University Fullerton; Estados Unidos.Fil: Zorreguieta, Angeles. Fundación Instituto Leloir; Argentina.A ca. 150-kbp Vibrio cholerae O1 biotype El Tor plasmid includes blaCTX-M-2 and a variant of aac(6 )-Ib within InV117, an orf513-bearing class 1 integron. InV117 is linked to a tnp1696 module in which IRl carries an insertion of IS4321R. The complete structure could be a potential mobile element

rmtD2, a New Allele of a 16S rRNA Methylase Gene, Has Been Present in Enterobacteriaceae Isolates from Argentina for More than a Decade ▿

The first allele of a 16S rRNA methyltransferase gene, rmtD2, conferring very high resistance to all clinically available aminoglycosides, was detected in 7/1,064 enterobacteria collected in 2007. rmtD2 was located on a conjugative plasmid in a Tn2670-like element inside a structure similar to that of rmtD1 but probably having an independent assembly. rmtD2 has been found since 1996 to 1998 mainly in Enterobacter and Citrobacter isolates, suggesting a possible reservoir in these genera. This presumption deserves monitoring by continuous surveillance

Complex Class 1 Integrons with Diverse Variable Regions, Including aac(6′)-Ib-cr, and a Novel Allele, qnrB10, Associated with ISCR1 in Clinical Enterobacterial Isolates from Argentina▿

Transferable quinolone resistance has not previously been reported in Argentina. Here we describe three complex class 1 integrons harboring the novel allele qnrB10 in a unique region downstream of orf513, one of them also containing aac(6′)-Ib-cr within the variable region of integrons. The three arrays differed from blaCTX-M-2-bearing integrons, which are broadly distributed in Argentina