Non- epidermidis coagulase-negative staphylococcal bacteremia: clinical predictors of true bacteremia.

In order to explore the clinical significance and risk factors for true bacteremia caused by coagulase-negative staphylococci (CNS) other than Staphylococcus epidermidis, a retrospective cohort study of 160 patients with at least one blood culture positive for non- epidermidis CNS was performed. True bacteremia was diagnosed in 32 (20%) of the patients. On multivariate analysis the following factors were associated with true bacteremia: (i) more than one positive blood culture, (ii) presence of a central venous catheter, and (iii) methicillin resistance. The results of this study indicate that non- epidermidis CNS can cause significant bloodstream infections.

Valproic acid increases cerebrospinal fluid zidovudine levels in a patient with AIDS.

Valproic acid is an anticonvulsant drug known to inhibit the glucuronidation of zidovudine (AZT) in human liver microsomes. Zidovudine is metabolized by glucuronidation to the inactive 5'-glucuronide with a short plasma half-life (1.0 +/- 0.2 hour). This case presentation confirms that valproic acid inhibits glucuronidation in vivo, and this is the first documented observation of increased cerebrospinal fluid levels of zidovudine because of an interaction with valproic acid in a patient with acquired immune deficiency syndrome (AIDS). The peak plasma AZT level for the control period was 119 ng/mL, which increased almost 3-fold to 344 ng/mL with valproic acid (1.5 g/day). The plasma AZT trough was 47 ng/mL, which also increased almost 3-fold to 124 ng/mL with valproic acid. The molar ratio of plasma 5'-glucuronide/AZT at the peak was reduced from 1.77 (control) to 1.07 with valproic acid. The 5'-glucuronide/AZT ratio at the trough was reduced markedly from 5.0 (control) to 0.93 with valproic acid, suggesting in vivo inhibition of glucuronidation. Cerebrospinal AZT levels, drawn 30 minutes after peak plasma levels, increased from 27 ng/mL for the control to 47 ng/mL with valproic acid, which paralleled the change in peak plasma concentrations. This interaction with valproic acid may contribute to higher AZT levels in the brains of patients with human immunodeficiency virus-related (HIV) encephalopathy.

Clinical manifestations and implications of coinfection with Mycobacterium kansasii and human immunodeficiency virus type 1.

We conducted a retrospective study to further elucidate the clinical presentations and prognosis of disease due to Mycobacterium kansasii in patients infected with human immunodeficiency virus (HIV). Forty-nine HIV-infected patients first had M. kansasii isolated at a mean CD4 cell count of 62/mm3 and at a mean interval of 17 months after the diagnosis of AIDS. Seventeen of the 49 patients had disseminated disease caused by M. kansasii. Twenty-nine patients had a positive acid-fast smear of sputum, and 35 were known to be cigarette smokers. At the time of initial isolation of M. kansasii, 13 patients had other concurrent pulmonary isolates and 15 had another mycobacterial species concurrently isolated (the Mycobacterium avium complex in 13 instances). Patients who received antimycobacterial treatment survived longer than those who did not. Only one of the 49 patients was definitively determined to be colonized with M. kansasii without disease; therefore, it appears that pulmonary isolates of M. kansasii in HIV-infected patients are almost always associated with disease. The increase in rates of M. kansasii disease among HIV-infected patients has paralleled the rise of AIDS in Louisiana. So far, this state has recorded more coinfections with M. kansasii and HIV than any other.

Pneumococcal bacteremia in cancer patients.

Twenty-eight episodes of Streptococcus pneumoniae bacteremia occurring in 27 cancer patients hospitalized in the Institut Jules Bordet between July 1979 and April 1985 were reviewed. Ten patients had hematological malignancies and 17 had solid tumors (in 7 cases, of the lung). Forty-four per cent of the patients were neutropenic (less than 1000/microliters) and 36% of the patients were in septic shock. In 36% of the patients no clinical source of S. pneumoniae bacteremia could be found. Seventy-nine (21% patients) received empirical antibiotic treatment containing a beta-lactam. Two patients who did not receive any empirical treatment died within 12 hours. Overall, 11/27 patients died within the first week, and 8/27 died within the first three days. Mortality in neutropenic patients was not different from that in non-neutropenic patients. In comparison with a similar study performed previously in our institution, there was no difference in incidence, type of patient, source of bacteremia, or mortality.

[A comparative review of combination therapy: 2 beta-lactams versus beta-lactam plus aminoglycoside]. / Ein vergleichender Uberblick zur Kombinationstherapie: Zwei beta-Laktame versus beta-Laktam plus Aminoglykosid.

We have reviewed the available literature on the controlled use of combinations of beta-lactams in the treatment of fever in neutropenic patients, as compared to that of combinations of beta-lactams and aminoglycosides. We compared overall responses, responses in septicemia and various other infections, according to different pathogens and degree of neutropenia, and we evaluated toxicity. Overall, these results showed that response rates with combinations of two beta-lactams are similar to those obtained with combinations of a beta-lactam and an aminoglycoside for infections in immunocompromised patients with serious underlying diseases. They also suggest that the emergence of resistance of pathogens to beta-lactams has often been coped by the use of newer drugs in infections caused by Enterobacteriaceae, but much less effectively in the case of Pseudomonas aeruginosa infections. There are still other important theoretical reasons for preferring an aminoglycoside-containing combination for empiric therapy in febrile neutropenic patients, and our overall conclusion is that a large-scale study comparing beta-lactam combinations to the traditional beta-lactam plus aminoglycoside regimens is mandatory.

Comparative review of combination therapy: two beta-lactams versus beta-lactam plus aminoglycoside.

Febrile neutropenic patients are usually treated with a combination of a beta-lactam and an aminoglycoside. Since Pseudomonas aeruginosa is an important pathogen in these patients, the empiric use of possibly synergistic combinations against that organism has been traditionally recommended. The recent appearance of beta-lactams more active against P. aeruginosa and the well-known nephrotoxicity of aminoglycosides have led some to advocate the use of beta-lactam combinations for empiric treatment of fever in neutropenic cancer patients. This article reviews the available literature on the controlled use of combinations of beta-lactams in the treatment of febrile neutropenic patients as compared with that of combinations of beta-lactams and aminoglycosides. The review includes comparison of overall response, response in patients with septicemia or other infections, response associated with different pathogens, the effect of profound neutropenia, and an evaluation of the toxicities encountered. Overall, these results show that response rates with a combination of two beta-lactams are similar to those obtained with the combinations of a beta-lactam and an aminoglycoside for infections in patients with serious underlying disease and compromised mechanisms of defense. They also suggest that the steady emergence of resistance of pathogens to beta-lactams has often been overcome by the use of newer drugs in regard to infections caused by the Enterobacteriaceae but much less effectively in regard to P. aeruginosa. There are still important theoretic reasons for preferring an aminoglycoside-containing combination as empiric therapy in febrile neutropenic patients, and our overall conclusion is that it would be appropriate to conduct a large-scale trial comparing beta-lactam combinations with the traditional beta-lactam plus aminoglycoside regimens in that setting.

Effect of increasing doses of amikacin with or without piperacillin in the serum bactericidal test.

To determine whether high doses of amikacin would prevent the development of resistance in clinical isolates, the serum bactericidal activity and killing rate of conventional and high doses of amikacin and piperacillin alone and in combination were measured in volunteer sera against a series of ten strains each of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Amikacin serum levels were 24.9 +/- 6.0 mg/l 1 h after infusion of the 7.5 mg/kg dose and 44.8 +/- 5.0 mg/l after the two-fold dose. Median serum bactericidal titers for low dose piperacillin + amikacin were 1:8-1:64 and for high-dose piperacillin + amikacin 1:16-1:128. Both were satisfactory, except against piperacillin-resistant Pseudomonas aeruginosa (median bactericidal titers less than or equal to 1:2), and both combinations had equivalent killing rates.

Emergence of resistance as a consequence of antimicrobial prophylaxis in immunocompromised patients.

Many authors in the literature have investigated the use of antibiotics in prophylaxis against infections in granulocytopenic patients. Two general methods have been used: one consists in trying to decontaminate the digestive tract in the hope of reducing the amount of microorganisms responsible for systemic infections. Another method is to use well-absorbed oral antibiotics, like trimethoprim-sulphamethoxazole, throughout the neutropenic period. It is considered critical to preserve as much as possible of the anaerobic flora, which is believed to provide protection against colonization by aerobic microorganisms or by fungi. Experimental and clinical evidence for this is critically reviewed. The efficacy of such methods has been variable, but there is also widespread fears that they could enhance selection of resistant organisms. We have reviewed the literature, specifically looking for data on the emergence of such resistant organisms, as well as data on changes in bacterial and fungal faecal flora.