Ceftazidime-resistant KkebsieUla pneumoniae strains began to appear when ceftazidime usage was increased in two unrelated Chicago hospitals. These strains produced a P-lactamase with an isoelectric point of 5.6 (RP-5.6) and strong hydrolyzing activity against ceftazidime. Two different restriction digest profiles were associated with the ceftazidime resistance plasmids. A second P-lactamase with a pl of 5.2 (RP-5.2) was coproduced in two representative strains. The second ,-lactamase hydrolyzed ceftazidime, cefotaxime, and aztreonam with relative hydrolysis rates of <8% of that observed for benzylpenicillin. Both enzymes were inhibited by clavulanic acid and tazobactam. Nucleotide sequencing of the genes coding for RP-5.2 and RP-5.6 revealed sequences identical to those of the TEM-12 and TEM-10 I8-lactamase genes, respectively. Both genes were derived from a TEM-1 sequence related to that of the gene encoded on the Tn2 transposon. Single point mutations are required to progress from TEM-1 to TEM-12 and from TEM-12 to TEM-10. Extracts from broths grown from single cell isolates of the strain producing TEM-12 and TEM-10 were shown to contain both enzymes. Transconjugants producing either the TEM-12 or the TEM-10 j-lactamase were obtained. A significant finding was that both enzymes were encoded by plasmids with identical restriction digest patterns.These studies show that mutations leading to extended-spectrum ,-lactamases can occur sequentially in the same organism, with the genes encoding both enzymes maintained stably.

HIV and malaria are among the leading causes of morbidity and mortality in sub-Saharan Africa, home to 10% of the world's population. An association between HIV and malaria is expected in theory, however, there is conflicting evidence regarding the impact of HIV infection on parasite loads. HIV-associated immunosuppression contributes to more frequent and more severe malaria and reduced efficacy of antimalarials in pregnant women and adults. These effects are modified by the endemicity and stability of malaria transmission. Co-infection with malaria and HIV in pregnant women is associated with anemia, low birth weight, and increased risk of infant mortality to a greater extent than infection with either disease alone. Studies investigating the impact of placental malaria on mother-to-child HIV-1 transmission continue to show conflicting results. This article attempts to review the pertinent information available about the interaction between HIV and malaria and information about chemoprophylaxis and treatment issues. Although much has been published in the last 10 years regarding the interaction of HIV and malaria in sub-Saharan Africa, we still need more information so as to understand the issues that will help us develop effective programs.

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Because it is an infection of the immunocompromised host, it may be considered an AIDS-defining illness. Several other similar cases have been reported in the literature.

Initiation of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) infection has changed the landscape of HIV/AIDS care. However, the potential for long-term complications from therapy has emerged, and the risk/benefit associated with usage now merits more extensive evaluation. As data from ongoing and future clinical trials continue to accumulate, individualization of therapy may be the appropriate option for HIV-infected individuals.

Since the introduction of the nucleoside reverse transcriptase inhibitor zidovudine in 1987, the number of the available antiretroviral medications has grown to about 20. Despite the efficacy of these medications, treatment-limiting adverse events are frequent. During the last several years, a new class of antiretroviral drugs often referred to as entry inhibitors, specifically the CCR5 blockers, have moved from the basic science laboratories and are now in the clinical phases of drug development. There are three agents in phase 2/3 development that inhibit viral entry by binding to CCR5, disrupting the interaction between the co-receptor and viral glycoprotein (gp) 120. They are aplaviroc (GW-873140), maraviroc (UK-427,857), and vicriviroc (SCH 417690). The development of these new antiviral agents that target different aspects of the viral life cycle is likely to make it possible to suppress viral strains that are resistant to the currently available antiretroviral drugs. There is a growing need for a new class of antiretrovirals with reduced toxicity and improved tolerability. However, currently available information suggests further pharmacokinetics, resistance, safety, and efficacy data are needed to understand how these agents may be effectively used in the clinical setting.

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Through a concerted effort to combat the human immunodeficiency virus (HIV) epidemic, researchers have made significant strides in molecular biology, virology, and immunology, which have resulted in an increased understanding of the complexities of this infection. The biggest obstacle to the success of current HIV therapy, however, is the emergence of viral resistance. Viral resistance is caused by mutations in the HIV-1 genome coding for structural changes in the target enzymes that can affect the binding or activity of the inhibitors. More information on the genetic basis of HIV resistance, mechanisms of viral variation, and therapeutic strategies for overcoming HIV resistance are needed. Sixty million people have been infected with HIV, 24 million have died, and it is projected that 200 million individuals will be infected by 2020.