Piperacillin plus amikacin therapy v carbenicillin plus amikacin therapy in febrile, granulocytopenic patients.

In a prospective randomized trial, febrile, granulocytopenic patients received either piperacillin sodium plus amikacin sulfate or carbenicillin disodium plus amikacin as initial empiric antimicrobial therapy. Although significantly more gram-negative aerobic bacilli isolated from initial cultures were susceptible to piperacillin than to carbenicillin (54 of 58 v 30 of 58), the overall response rates for the two regimens were similar (113 of 143 or 79% for piperacillin plus amikacin and 116 of 154 or 75% for carbenicillin plus amikacin). Piperacillin plus amikacin was associated with less hypokalemia (26 of 143 v 56 of 154). Nephrotoxicity, which was minimal with both regimens, developed less frequently in patients receiving carbenicillin plus amikacin (12 of 143 v two of 154). These results suggest that the overall efficacy of piperacillin plus amikacin is similar to carbenicillin plus amikacin and that piperacillin plus amikacin may be associated with less hypokalemia but more nephrotoxicity.

Coccidioidal meningitis. An analysis of thirty-one cases and review of the literature.

Clinical and laboratory features of 31 patients with coccidioidal meningitis seen from January 1964 through December 1976 with follow-up through 1979 are reported and data on 114 patients from the literature reviewed. History of exposure to C. immitis, a wide age range, and, in about one third, underlying conditions are noteworthy. Dissemination to the meninges usually occurs within the first few months although diagnosis is frequently delayed. Presenting symptoms and signs of coccidioidal meningitis are varied but signs of chronic meningitis or suggestion of hydrocephalus are prominent. Evidence of acute infection is unusual even with widespread disease. Diagnosis is usually made by demonstration of coccidioidal CF antibodies in the CSF although they are not found in all patients. Some show other direct evidence of C. immitis. Special diagnostic techniques such as CAT scanning for evidence of basilar meningitis or hydrocephalus are valuable. Amphotericin B remains the drug of choice despite the need for long-term therapy and the problems with intrathecal administration. Reservoirs are only occasionally useful but shunts are frequently lifesaving despite complications. Factors associated with a bad prognosis are hydrocephalus, non-Caucasian race, or presence of an underlying disease.

Simultaneous antibiotic levels in "breakthrough" gram-negative rod bacteremia.

Of 237 cases of gram-negative rod bacteremia observed at the UCLA Medical Center during a 12 month period, 52 (22 per cent) occurred while the patient was receiving antibiotics which inhibited the infecting organism by disc diffusion tests. One half of the plasma samples available from 42 such patients with "breakthrough" bacteremia had subinhibitory circulating antibiotic levels when cultures were positive. Sepsis documented within 72 hours of initiation of therapy was usually due to antibiotic-sensitive Esch. coli and was associated with inadequate antibiotic levels; the patient was usually treated with a penicillin or cephalosporin. The source of bacteremia was most frequently the urinary tract or the biliary tree. In contrast, sepsis occurring more than 72 hours after the administration of antibiotics was frequently caused by multiple antibiotic-resistant Esch. coli in patients treated with gentamicin in adequate dosage and was associated with leukopenia or undrained purulent collections. Therapy ultimately failed in 20 cases (48 per cent): in early "breakthrough" bacteremia, failure was associated with subinhibitory antibiotic levels, and in late "breakthrough" bacteremias with inadequate drainage or impaired host defenses.

Suppurative thrombophlebitis due to Aeromonas.

A patient developed lethal suppurative thrombophlebitis and adjacent soft-tissue infection caused by Aeromonas. Potential risk factors included corticosteroid therapy and the use of warm tap water compresses at the site of intravenous catheter-related phlebitis. This case demonstrates the rapidly invasive characteristics of Aeromonas and the need for early surgical intervention in suppurative thrombophlebitis.

Infectious osteitis pubis.

Osteitis pubis is a well-recognized painful inflammation involving the structures of the anterior half of the pelvic girdle, but its cause remains controversial. Biopsy and culture of the pubic bone in 3 patients with osteitis pubis after implantation of a urinary anti-incontinence device were consistent with pubic osteomyelitis which responded to antibiotic therapy. Infection was also found in almost all previously reported cases of osteitis pubis subjected to similar biopsy and culture. Bone biopsy and culture should be strongly considered before initiating frequently unsuccessful empirical therapy in patients with osteitis pubis.

125I-Radioimmunoassay of amikacin and comparison with a microbioassay.

A radioimmunoassay (RIA) has been developed using 125I-amikacin. Amikacin was iodinated by a modified BOLTON and HUNTER method. Dextran-charcoal was used to separate bound from free drug. The standard curve was linear on a logit-log plot in the range of 0.5 ng to 4 ng amikacin per tube. There was no cross-reactivity of amikacin antisera to the amino-glycosides gentamicin, tobramycin, netilmicin, and sisomicin but a 70% cross-reaction was observed with kanamycin, the compound from which amikacin is synthetically derived. Correlation of the RIA with a microbioassay for the determination of serum amikacin levels in 18 patient samples was excellent (r = 0.94). This new RIA technique is more sensitive, rapid, versatile, and less costly than the RIA using 3H-amikacin, and is far more sensitive and faster than microbioassay.

Clinical implications of the presence of drug residues in food.

Untoward clinical effects in man of drugs or chemicals as food residues might occur from direct pharmacological action, stimulation of hypersensitivity, or effects on cell regulatory processes. Antimicrobial residues might also influence the normal bacterial microflora of the skin, mucous membranes, and gastromintestinal tract. No direct evidence exists to incriminate antimicrobial drug food residues in any of these events. The permissible residues of antimicrobial substances are so low and the assay procedures for detecting them so sensitive that adequate surveillance should preclude harmful effects in man from these agents. Problems still remain with respect to potential carcinogenicity of drugs and chemicals as food residues.

Activity of five aminoglycoside antibiotics in vitro against gram-negative bacilli and Staphylococcus aureus.

The in vitro susceptibility to BB-K8, butirosin, gentamicin, sisomicin, and tobramycin of seven groups of clinically significant gram-negative bacilli and Staphylococcus aureus was assessed by using the International Collaborative Study-World Health Organization criteria. The activity of gentamicin, sisomicin, and tobramycin generally paralleled each other. Sisomicin was the most potent compound by weight and usually demonstrated the most rapid rate of killing. BB-K8 and butirosin were less potent, but higher serum levels may be achieved with these agents. BB-K8 generally showed the greatest ratio between achieveable mean peak serum levels and concentrations needed to inhibit [Formula: see text] of each group of organisms tested. Additionally, BB-K8 was active against six of seven highly gentamicin-resistant strains. All of these antibiotics showed diminished activity at pH 6.4 but only gentamicin and sisomicin showed occasionally enhanced activity at pH 8.4.

Activity of three aminoglycosides and two penicillins against four species of gram-negative bacilli.

Three aminoglycoside antibiotics and two penicillins were compared for their in vitro activity against 60 isolates of Serratia, Pseudomonas, Proteus mirabilis, and indole-positive Proteus sp. Testing was done by the agar dilution method using Mueller-Hinton broth solidified with 1.5% agar. The activity of amikacin, aminodeoxybutirosin, and gentamicin against Proteus and Pseudomonas, as related to their peak blood levels, showed no significant differences. Amikacin was the most active against Serratia marcescens. Results using Mueller-Hinton media in broth dilution tests correlated with the agar dilution method except for Pseudomonas aeruginosa. The minimal inhibitory concentration for aminoglycosides in agar was considerably greater than the minimal inhibitory concentration in Mueller-Hinton broth, and the disparity was related to the higher divalent cation concentration of agar. BL-P1654 and carbenicillin were similar except that carbenicillin was much more active against indole-positive Proteus sp. Additionally, the ratio of bactericidal to bacteriostatic concentrations of BL-P1654 was considerably greater than for carbenicillin.

Improved acetylating radioenzymatic assay of amikacin, tobramycin, and sisomicin in serum.

The acetylating radioenzymatic assay of aminoglycosides was modified by using [(3)H]acetyl coenzyme A as cosubstrate. This modification reduces the cost of the method by at least one-half without sacrificing rapidity or accuracy.