We compared results of MIC and disk susceptibility tests on Haemophilus test medium (HTM) and those on comparative media. Ampicillin MICs were determined with seven ampicillin-resistant, non-f-lactamaseproducing (AmprNBLP) isolates by using HTM and supplemented brain heart infusion (sBHI) agar. Ampicilli and amoxicillin-clavulanate disk tests with 16 Amp'NBLP strains, 18 ampicillin-susceptible (Amps) isolates, and 17 ampicillin-resistant, .lactamase-producing (AmprBLP) strains were performed by using five media: laboratory-prepared HTM (PHTM), commercial HTM (CHTM), sBHI, enriched chocolate agar, and Mueller-Einton chocolate agar. We observed that five of seven and three of seven Amp'NBLP stains were misclassified as susceptible with PHTM (MIC, <2 ,ug/ml) with inocula of 103 and 1i@ CFU, respectively, but were resistant with sBHI (MIC,.2 ,ug/ml (.25 mm) and resistance (<21 mm) (1, 9). Presumably, these changes would allow identification of all ampicillin-resistant strains by using the standard 10-,ug ampicillin disk test. Previously, we showed with the former NCCLS criteria (7) and media that the 10-pLg disk test, in contrast to the 2-,ug ampicillin disk test, failed to detect 44% (8 of 18) of ampicillin-resistant, non-p-lactamase-producing (AmprNBLP) isolates; these isolates have an intermediate level of resistance compared with 3-lactamase-producing strains (median ampicillin MIC, 8 versus 32 p.g/ml, respectively, with an inoculum of 105 CFU) (4).Recently, we used HTM to compare the in vitro susceptibility of H. influenzae to three cephem antibiotics (6). In that study, we observed that the ampicillin MICs with HTM were lower for AmprNBLP strains compared with our previous data obtained with the same isolates in our laboratory when we used supplemented brain heart infusion medium (sBHI; Difco Laboratories, Detroit, Mich.); those data prompted this investigation. We compared the ampicillin MICs using HTM (2)

Analgesic-antipyretic agents and nonsteroidal anti-inflammatory drugs are the most commonly used medications worldwide for the treatment of pain and fever in children. Acute renal failure is commonly seen in adults after treatment with analgesic agents. This complication has rarely been reported in children. Here, we describe 2 patients admitted to our hospital with acute nonoliguric renal failure temporally associated with ingestion of analgesic-antipyretic drugs at therapeutic doses. The first case was a 16-year-old adolescent boy, who had taken acetaminophen (APAP) and mefenamic acid for the indication of upper respiratory tract infection with daily doses of 1500 and 500 mg, respectively. His serum urea nitrogen and creatinine values were 16 and 1.6 mg/dL. The second case was a 12-year-old boy, who had taken APAP with a daily dose of 500 mg for abdominal pain. His serum urea nitrogen and creatinine values were 21 and 2.29 mg/dL. Both of them recovered with appropriate hydration within a week. Over-the-counter analgesic-antipyretic agents seem innocent but carry the risk of acute renal failure even at therapeutic doses. We believe that increased caution and awareness of the toxic effects of APAP and nonsteroidal anti-inflammatory drugs are needed. We suggest that clinicians should be careful while using analgesic-antipyretic-anti-inflammatory drugs especially in children with subclinical dehydration.

A 10-year-old boy presented with nuchal rigidity and cerebrospinal fluid (CSF) leukocytosis initially and again on day 6 of intravenous cefuroxime therapy (200 mg/kg/day). Both CSF specimens yielded nontypable beta-lactamase-negative Haemophilus influenzae that were susceptible by disk tests but relatively resistant to cefuroxime (MIC, 8- to 16-fold greater than that of control isolates). To define the mechanism of resistance, the cefuroxime resistance marker was transformed to a susceptible H. influenzae recipient; inactivation and permeability of beta-lactam substrate were tested and the penicillin-binding protein (PBP) profiles were examined. Inactivation of beta-lactam substrate was not detected and reduced permeability was not found. However, reduced beta-lactam binding to PBPs 4 and 5 was observed; 18- to 27-fold more penicillin and 2.5-to 4-fold more cefuroxime was required to saturate or block 50% of the binding sites of these PBPs, respectively. Thus, reduced affinity of PBPs 4 and 5 for beta-lactam substrate appears to be the mechanism of cefuroxime resistance in this strain. The reduced affinity of these targets appears to have contributed to the bacteriologic and clinical failure in this patient.