IDCP SNAPSHOTS (2001)

March/April 2001 Infliximab and Opportunistic Fungal Infections A letter to the editor of the New England Journal of Medicine (Warris et al, 2001; 344:1099– 2000) reports the case of a patient with Crohn’s disease who developed invasive pulmonary aspergillosis after a single injection of infliximab, the anti-TNF antibody. The patient had no other risk factors; he was not neutropenic and was not receiving corticosteroids. The manufacturer responded that, in clinical trials involving more than 2000 patients, only two had had fungal infections: one had extenuating factors and the other may have been receiving a placebo rather than an active drug. Among 115,000 patients treated after the drug was released, there have been reports of six patients with aspergillosis, five cases of Pneumocystis carinii pneumonia, three cases of histoplasmosis, and a few other fungal infections. In almost all of these cases, other immunosuppressive agents were given as well. Thus, it may be that there is no appreciable predisposition to fungal infection in recipients of infliximab–but the case reported above is impressive. Why Is Osteomyelitis Painful? The cause of the pain of osteoarthritis is somewhat unclear. Cartilage, the main site of damage in this disease, lacks nerve endings. Pain could originate in a number of other structures around the joint (synovium, capsule, ligaments, and muscles). The pain of osteoarthritis does not correspond to the extent of joint damage (loss of cartilage or eburnation). However, it does correspond well to the extent of edema in the subarticular bone marrow on T 2 -weighted MRI images as was shown by Felson and colleagues (Ann Intern Med 2001; 134:541–9). Edema of the bone marrow has also been shown to occur in patients with bone trauma and avascular necrosis of the femoral head. In these cases, the edema is an inflammatory response to stress. It occurs to this reader that inflammatory edema of the bone marrow may be an explanation for at least some of the pain associated with hematogenous osteomyelitis. Precisely which nerve endings would react to the edema as a painful stimulus is not clear. Congenital CMV Infection in Mothers with Preconceptional Immunity Several studies have suggested that symptomatic congenital CMV infection is rare in the infants of mothers with preexisting CMV immunity, but others have concluded that preconceptional immunity against CMV is only partial. When congenital infections occur in this setting, it has been unclear if they arise from reactivation of the endogenous strain of CMV or from infection by a new strain. In a recent study, serum from sixteen mothers who delivered congenitally infected children despite having had preexisting antibodies to CMV were examined (Boppana et al, New Eng J Med 2001; 344: 1366–71). In ten of these sixteen (62%), there was serological evidence of infection by a new strain of CMV. It is tempting to ask whether some of the infections in immunocompromised adults, such as those with transplanted organs or with HIV infection, may also be due to infection by new strains rather than endogenous reactivation. In the case of congenital infections, it was necessary to resort to serum antibody specificity to distinguish a new infecting strain from reactivation because it is difficult to culture the virus from these infections. However, in the case of immunocompromised adults, it should be relatively easy to obtain viral isolates from sequential episodes for comparison. Effects of Imipenem on EEGs of Rats An elegant study by French investigators (Dupuis et al, Antimicrob Ag Chemother 2001; 45:1682) showed that infusion of imipenem produced EEG abnormalities together with tremors and partial seizures in rats. There was a delay of about 30 mins between the attainment of peak serum concentrations and the peak EEG effect. This delay could be attributed to slowness in transfer of the drug from serum into the central nervous system compartment. A complex pharmacokinetic model was shown to fit the observed phenomena. The analysis demonstrated that elimination from the central nervous system was much slower than from the “central compartment.” The same investigators have used this EEG model to assess the epileptogenic potential of fluoroquinolones. It seems to be an excellent screening tool to assess the mechanisms and pharmacodynamic characteristics of epileptogenic drugs.