Kenneth V.I. Rolston

Role of Clindamycin in the Treatment of Central Nervous System Toxoplasmosis

Three patients with acquired immune deficiency syndrome (AIDS), central nervous system toxoplasmosis, and hypersensitivity to sulfadiazine were given treatment with clindamycin plus pyrimethamine. All three showed improvement clinically with resolution of symptoms. Two patients had computed tomographic evidence of improvement with reduction in size or clearing of cerebral lesions and the third had resolution of chorioretinitis. Another patient who had a relapse during administration of standard therapy (pyrimethamine plus sulfadiazine) had a clinical response when clindamycin was added to this regimen. Clindamycin in combination with pyrimethamine, or as an adjunct to standard therapy, may be useful in the treatment of central nervous system toxoplasmosis in patients with AIDS.

Comparative in vitro activity of cefpirome and other antimicrobial agents against isolates from cancer patients.

Cefpirome and six other antimicrobial agents were tested against 884 blood culture isolates from cancer patients. Cefpirome was highly active against aerobic gram-negative bacilli including Acinetobacter spp., and the Enterobacteriaceae. Only imipenem was more active than cefpirome against Pseudomonas aeruginosa. Cefpirome was also extremely active against beta-hemolytic streptococci and methicillin-susceptible staphylococci.

Activity of newer antimicrobial agents against Aeromonas hydrophila.

Augmentin can be administered orally and is excreted by the renal route. After administration of a 375 mg oral dose (125 mg clavulanic acid and 250 mg amoxicillin), serum levels reach about 4 mg/1 of amoxicillin and 2.5 mg/1 of clavulanic acid. Two hours after administration of 750 mg of augmentin (500 mg amoxiciUin and 250 mg clavulanic acid) the mean serum concentration of amoxicillin reaches a peak of 8.1 mg/1. The mean concentration o f clavulanic acid reaches a concentration o f 5.2 mg/1 one hour after a dose.

Ambulatory management of varicella-zoster virus infection in immunocompromised cancer patients

Abstractu2002Immunocompromised patients with varicella-zoster virus (VZV) infection are at greater risk for dissemination and the development of complications than immunocompetent individuals. Consequently, they are generally hospitalized in strict isolation rooms and treated with parenterally administered acyclovir. Although effective, this approach is expensive and creates logistic difficulties in the hospital. We treated 38 immunosuppressed cancer patients presenting to our ambulatory treatment center with VZV infections with intravenous acyclovir (500u2009mg/m2 8-hourly) in an ambulatory/home setting. Patients were monitored for success or failure of therapy, progression of infection, development of complications or drug toxicity, and satisfaction/compliance with therapy. Most patients (33, or 87%) responded to therapy. Among the failures, 2 patients had progressive VZV infection, 2 were hospitalized due to renal toxicity, and 1 developed a superinfection. All patients eventually responded and there were no deaths on this study. Two patients relapsed within 1 month of initial response. Both responded to retreatment with acyclovir, without hospitalization. The median duration of parenteral therapy with acyclovir was 7.5 days. Seven patients (18%) had to be switched to oral acyclovir (800u2009mg, 5 times a day) before complete response, owing to problems with venous access. All 7 completed therapy successfully. Overall, patients expressed a high level of satisfaction with outpatient therapy, and there were no instances of noncompliance or patient requests for withdrawal from study. The results of this study indicate that VZV infections in clinically stable immunosuppressed cancer patients are relatively benign and do not require hospitalization. Parenterally administered acyclovir in an ambulatory setting is effective therapy for such infections.

Formal adult infectious disease specialist consultations in the outpatient setting at a comprehensive cancer center (1998-2008): Diverse and impactful

PurposeThe literature on the impact of infectious disease (ID) consulations in the outpatient treatment of cancer is scarce.MethodsThe medical records of consecutive adult patients with cancer formally evaluated by two board-certified ID specialists in an outpatient setting at our institution over a 10-year period (1998–2008) were reviewed retrospectively. The patients demographics, referring departments, purposes for consultation, ID specialist recommendations, and overall impact of consultations on outcome were analyzed.ResultsWe identified 598 patients who underwent ID specialist consultations. Most of them had solid tumors (53%), predominantly breast cancer, whereas non-Hodgkins lymphoma was the most common hematologic malignancy. Almost half of the patients (45%) had active malignancies, but few of them were severely neutropenic (8%) or had been receiving high doses of corticosteroids (17%). The most frequent requests for consultation were culture or serologic test (15%), and treatment of cellulitis and/or surgical wound infections (14%). Of 337 isolated pathogens, the most prevalent were methicillin-resistant Staphylococcus aureus (13%) and Pseudomonas aeruginosa (8%), as well as atypical mycobacteria (16%) and Aspergillus species (11%). ID specialists provided alternative diagnoses in 53% of the cases, including identification of a different infection (46%), a noninfectious etiology (29%), colonization (16%), and drug-related toxic effects (9%). Overall, we deemed the contribution of the ID specialist to be significant in 62% of the consultations.ConclusionsID specialists contribute significantly to the outpatient care of individuals with cancer.

Pseudomonas Aeruginosa Infections in Cancer Patients

Cancer patients, particularly those with neutropenia, are at increased risk of developing bacterial infections (1). In the four decades since the association between neutropenia and infection was recognized, the epidemiology of bacterial infection in cancer patients has undergone several changes, with gram-positive organisms and gram-negative bacilli being the predominant pathogens at different stages. Many of these epidemiologic shifts have been influenced by changes in the nature and intensity of chemotherapeutic and immunosuppressive regimens, prophylactic and empiric antimicrobial regimens, and the increased usage of vascular access catheters and prosthetic devices (2,3).Pseudomonas aeruginosa emerged as a common cause of gram-negative infection in cancer patients during the 1960’s and, before the availability of agents such as carbenicillin, was associated with mortality rates in excess of 90% (4). Since then, the availability of potent anti-pseudomonal agents and significant improvements in supportive care have reduced the mortality to approximately 25–30% (5,6). Substantial regional and institutional variations in the frequency of infections caused by P. aeruginosa have been documented (7,8). The treatment of P. aeruginosa infections continues to foster much discussion and debate among various experts, some of whom advocate the use of synergistic, bactericidal combinations for the treatment of all pseudomonal infection in neutropenic patients, whereas others do not. These issues will be discussed in this chapter, with an emphasis on current trends in North America.

Nature and outcome of febrile episodes in patients with pancreatic and hepatobiliary cancer.

Fifty febrile episodes in patients with hepatobiliary and pancreatic cancer were reviewed. Biliary obstruction often resulting in cholangitis was an important predisposing factor, whereas neutropenia (<500 PMN/mm3) was uncommon (10%). Microbiologically documented infections originating from the gastrointestinal tract were predominant, with Enterococcus faecalis and Escherichia coli being isolated most often. Non-infectious causes of fever occurred in 16% of patients. Only one patient developed a fungal infection. The overall response rate to therapy was 94%, with 32% being eligible for outpatient management. These date are quite different from those generated from patients with hematologic malignancies and indicate that disease-site specific management guidelines need to be developed for febrile episodes in patients with various underlying neoplasms.

Comparative in vitro activity of the new erythromycin derivative dirithromycin against gram-positive bacteria isolated from cancer patients

The in vitro activity of dirithromycin (LY-237216), a new macrolide erythromycin derivative, was compared to that of four other agents (clarithromycin, erythromycin, roxithromycin, clindamycin) against 334 gram-positive isolates obtained from cancer patients. Dirithromycin was similar in potency and antimicrobial spectrum to the other agents tested. It was very active against beta-haemolytic streptococci andStreptococcus pneumoniae, and moderately active against penicillin and methicillin susceptibleStaphylococcus aureus, Bacillus spp.,Listeria monocytogenes andCorynebacterium jeikeium. Erythromycin resistant organisms were also resistant to dirithromycin.

Activity of new antimicrobial agents against Listeria monocytogenes

LY146032 is a new antimicrobiai agent belonging to the group of acid lipopeptide antibiotics. The antibacterial action of LY 146032 results from interruption of cell wall synthesis at a point in the synthetic pathway different from those known to be the sites of action ofbeta-lactam antibiotics and glycopeptides. LY 146032 has excellent antibacterial activity against gram-positive microorganisms including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus faecalis, Corynebacterium JK species, Listeria monocytogenes and Clostridium difficile (1). Recent investigations have shown that the MICs of LY146032 and vancomycin against Clostridium difficile isolates are about the same (2). In the present study the efficacy of LY 146032 was compared with that of vancomycin in a hamster model of colitis caused by Ctostridium difficile.

Clinical pharmacology of timentin (ticarcillin and clavulanic acid)

Ticarcillin (4 gm) and clavulanic acid (0.1 gm) were simultaneously administered as timentin to patients with cancer as therapy for infections. The pharmacokinetics of both ticarcillin and clavulanic acid were studied in 15 patients after 30‐minute and 2‐hour intravenous infusions. The mean (±SD) ticarcillin plasma peak concentrations after the two infusions were 341 ± 76 and 210 ± 60 µg/ml. The plasma terminal t½ values of ticarcillin were 80 ± 32 and 56 ± 12 minutes. The AUCs were 631 ± 189 and 601 ± 230 mg/L · hr. The volumes of distribution of the area were 15 ± 5 and 21 ± 7 L and total clearances were 115 ± 36 and 127 ± 54 ml/min. The corresponding values for clavulanic acid after the infusions are as follows: mean peak concentrations, 5 ± 1 and 4 ± 1 µg/ml; plasma terminal t½ values, 84 ± 24 and 74 ± 36 minutes; AUCs, 11 ± 3 and 11 ± 6 mg/L · hr; volumes of distribution of the area, 22 ± 3 and 32 ± 6 L; and total clearances, 170 ± 58 and 175 ± 68 ml/min.