The Clinical and Laboratory Standards Institute has recommended that Enterobacteriaceae susceptibility to most cephalosporins and carbapenems be reported according to minimum inhibitory concentration (MIC) alone. We analyzed our record of multi-drug resistant Enterobacteriaceae to assess the impact of these changes. We compared susceptibilities of ceftriaxone-resistant Enterobacteriaceae when using the 2009 and new 2010 MIC standards. Vitek2® (BioMerieux), was used to assess the changes in susceptibility. Klebsiella pneumoniae, Proteus sp., and Escherichia coli were the major species from urine, sputum, blood, and other sterile sites. The new breakpoint for cephalosporins increased resistance in E. coli and P. mirabilis. Many Proteus categorized as resistant by extended-spectrum beta-lactamase (ESBL) detection or inferred resistance have MICs to ceftriaxone ≤ 1 mcg/ml. New carbapenem breakpoints increased resistant Klebsiella pneumoniae and Proteus mirabilis. The increased ceftriaxone resistance from lowering breakpoints was almost balanced by the loss of resistance in ESBL isolates with MICs ≤ 1 mcg/ml. MIC-based susceptibility for multi-drug resistant Enterobacteriaceae increases the number of resistant isolates. Inferring mechanisms of resistance has a disproportionate effect on the susceptibility of Proteus mirabilis to cephalosporins, and the MIC-based standard has an almost equivalent but opposite effect on Proteus mirabilis susceptibility to carbapenems.

Until a decade ago, clinicians could use epidemiological clues to select empirical therapy for methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant S. aureus (MRSA) ([5][1]). The emergence of MRSA as a community pathogen and the documentation of the inferiority of non-beta-

Multiple HIV-1 subtypes and circulating recombinant forms (CRFs) are known to cocirculate in Africa. In West Africa, the high prevalence of CRF02_AG, and cocirculation of subtype A, CRF01_AE, CRF06_cpx, and other complex intersubtype recombinants has been well documented. Mali, situated in the heart of West Africa, is likely to be affected by the spread of recombinant subtypes. However, the dynamics of the spread of HIV-1 recombinant subtypes as well as nonrecombinant HIV-1 group M subtypes in this area have not been systematically assessed. Herein, we undertook genetic analyses on full-length env sequences derived from HIV-1-infected individuals living in the capital city of Mali, Bamako. Of 23 samples we examined, 16 were classified as CRF02_AG and three had a subsubtype A3. Among the remaining HIV-1 strains, CRF06_cpx and CRF09_cpx were each found in two patients. Comparison of phylogenies for six matched pol and full-length env sequences revealed that two strains had discordant subtype/CRF designations between the pol and env regions: one had A3 pol CRF02_AG env and the other had CRF02_AG pol A3 env. Taken together, our study demonstrated the high prevalence of CRF02_AG and complexity of circulating HIV-1 strains in Mali. It also provided evidence of ongoing virus evolution of CRF02_AG, as illustrated by the emergence of more complex CRF02_AG/A3 intersubtype recombinants in this area.

China is a region of the world with a rapidly spreading HIV-1 epidemic. Studies providing insights into HIV-1 pathogenesis in infected Chinese are urgently needed to support the design and testing of an effective HIV-1 vaccine for this population. HIV-1-specific T cell responses were characterized in 32 HIV-1-infected individuals of Chinese origin and compared to 34 infected caucasians using 410 overlapping peptides spanning the entire HIV-1 clade B consensus sequence in an IFN-gamma ELISpot assay. All HIV-1 proteins were targeted with similar frequency in both populations and all study subjects recognized at least one overlapping peptide. HIV-1-specific T cell responses clustered in seven different regions of the HIV-1 genome in the Chinese cohort and in nine different regions in the caucasian cohort. The dominant HLA class I alleles expressed in the two populations differed significantly, and differences in epitope clustering pattern were shown to be influenced by differences in class I alleles that restrict immunodominant epitopes. These studies demonstrate that the clustering of HIV-1-specific T cell responses is influenced by the genetic HLA class I background in the study populations. The design and testing of candidate vaccines to fight the rapidly growing HIV-1 epidemic must therefore take the HLA genetics of the population into account as specific regions of the virus can be expected to be differentially targeted in ethnically diverse populations.

Chimeric simian-human immunodeficiency viruses (SHIVs) carrying envelope glycoproteins derived from a T cell-macrophage dual-tropic primary isolate (human immunodeficiency virus type 1 [HIV-1] strain DH12) were constructed. When inoculated into macaque monkeys, SHIV(MD14) carrying simian immunodeficiency virus-derived nef established significantly higher virus loads than did SHIV(MD1), which contains the HIV-1 nef gene. Three patterns of CD4 cell depletion were observed in infected monkeys: exponential and irreversible loss to undetectable levels within 10 weeks of infection; marked reduction during acute infection followed by partial recovery and stabilization (lasting from 10 weeks to > 1 year), with a later decline to undetectable levels in some animals; and a transient loss during acute infection. The induced immunodeficiency was accompanied by CD4 cell counts of < 50 cells/microL and was associated with Pneumocystis carinii pneumonia, cytomegalovirus meningoencephalitis, lymphoid depletion, and thymic atrophy.

Aspergills fumigatus produces conidia that arehighly dispersable andresistant todegradation. We have sought toanalyze these properties bystudying therodlets which formtheouter sporecoatprotein. Degenerate primers based on hydrophobins inother fungi were applied togenomic DNA fromA.fumigatus inPCR.A product ofthis reaction withsimilarity toanAspergiUus nidukins geneasjudged bySouthern hybridization was chosen forfurther study. Cloning andsequencing revealed a genewithtwointrons whichencodes aprotein of 159aminoacids. Structural characteristics consistent withthose ofother fungal hydrophobin genes,especially conserved cysteine residues, arepresent. Theexpression ofthegeneislimited tothedevelopmental stages in whichmaturing conidiophores arepresent. ThisA.fiumigatus gene,HYP), was usedtotransform a mutant strain ofA.nidudans thatlacks rodlets. Transformants with a single copyofHYPIexpressed a rodlet layer on their conidia asobserved byfreeze-fracture electron microscopy.