Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections.

The steady increase in resistant organisms is related to the widespread use of antibiotics in community and hospital settings. New therapeutic options are needed, including treatments for infections caused by antibiotic-resistant gram-positive organisms. Quinupristin-dalfopristin, the first formulation of a distinct class of antibiotics known as the streptogramins, has activity against a range of gram-positive bacteria that are usually resistant to other agents, including vancomycin-resistant Enterococcus faecium. The pharmacodynamic (postantibiotic effect) and pharmacokinetic characteristics of quinupristin-dalfopristin allow dosing at eight- to 12-hour intervals. The safety profile of the formulation is generally favorable, with no demonstrable ototoxicity, nephrotoxicity, bone marrow suppression, or cardiovascular adverse effects. Reversible arthralgias, myalgias, and peripheral venous irritation are the formulation's major side effects. A potential for drug interactions exists because quinupristin-dalfopristin significantly inhibits the cytochrome P450-3A4 enzyme system. Quinupristin-dalfopristin has been shown to be effective in the management of documented severe infections caused by vancomycin-resistant E. faecium, nosocomial pneumonia, and infections related to the use of intravascular catheters.

Frequency of low-level bacteremia in children from birth to fifteen years of age.

A single blood culture inoculated with a small volume of blood is still frequently being used for the diagnosis of bacteremia in children because of the continued belief by many that bacteria are usually found in high concentrations in the blood of pediatric patients with sepsis. To determine the importance of both blood volume cultured and the number of culture devices required for the reliable detection of pathogens in our pediatric population, blood from children from birth to 15 years of age and with suspected bacteremia at York Hospital (a 500-bed community hospital) was inoculated into at least a Pediatric Isolator (Wampole Laboratories; 1.5 ml of blood) or a standard Isolator (10 ml of blood) and a bottle of ESP anaerobic broth (Trek Diagnostic Systems; 0.5 to 10 ml of blood). The use of a second Isolator and additional aerobic and anaerobic bottles and the total blood volume recommended for cultures (2 to 60 ml) depended on the weight and total blood volume of each patient. One hundred forty-seven pathogens were recovered from the blood of 137 (3.6%) of 3,829 children for whom culturing was done. Of 121 septic episodes for which the concentration of pathogens in the blood could be determined using Isolators, 73 (60. 3%) represented low-level bacteremia (

Occurrence and documentation of low-level bacteremia in a community hospital's patient population.

To document the incidence of low-level bacteremia in the patient population of this study, two blood culture sets were collected from symptomatic patients weighing more than 80 pounds. Each blood culture set consisted of a lysis-centrifugation tube and three bottles containing different culture broths, each inoculated with 10 mL blood. Pathogens from 63 (26.4%) and 48 (20.1%) of the 239 culture-positive patients were recovered from only one and two of the eight culture devices, respectively, representing low-level bacteremia. Isolates from another 60 (25.1%) of the 239 patients were recovered from all eight of the culture devices, representing high-level bacteremia. Whether patients had low-level or high-level bacteremia, there were mostly insignificant differences in the types of species recovered, in the percentages of patients for whom therapy was initiated or changed following the laboratory's reports, and in the clinical signs, symptoms, and characteristics of the patients. Clinically documented, low-level bacteremia is relatively common in this community hospital's patient population. Culturing of up to 80 mL of blood was required for detection of all pathogens from patients weighing more than 80 pounds.

Parenteral beta-lactamase inhibitor combinations for clinical use.

Beta-lactamase enzymes are commonly produced by staphylococci, the Enterobacteriaceae, Pseudomonas aeruginosa and certain anaerobic organisms, such as Bacteroides fragilis. The production of beta lactamases is an important mechanism through which bacteria become resistant to antibiotics. The currently marketed beta-lactamase inhibitor combinations include ampicillin-sulbactam, ticarcillin-clavulanate potassium and, more recently, piperacillin-tazobactam. These extended spectrum antibiotic combinations share the ability to inhibit methicillin-susceptible staphylococci, nearly all anaerobic bacteria and many Enterobacteriaceae. Ticarcillin-clavulanate potassium and piperacillin-tazobactam also have activity against P. aeruginosa. The combination agents are useful in the treatment of moderate to severe infections, particularly when a polymicrobial etiology is suspected or documented.

Corynebacterium pseudodiphtheriticum: a respiratory tract pathogen in adults.

Corynebacterium pseudodiphtheriticum has been reported to be an uncommon respiratory pathogen. We describe the clinical and microbiologic features of 17 patients from whose sputum C. pseudodiphtheriticum was isolated. Patients were identified through a review of the reports from the clinical microbiology laboratory at York Hospital, a community teaching hospital, from October 1990 through April 1993; 17 patients with respiratory infection caused by C. pseudodiphthriticum were identified. There were 12 cases of bronchitis and five of pneumonia. An underlying systemic condition, particularly congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, or malignancy, was common. Onset of symptomatology was acute for most patients, but fever was noticeably absent in almost two-thirds of the cases. Isolates were uniformly susceptible to the beta-lactam antibiotics, vancomycin, and trimethoprim-sulfamethoxazole, but resistance to clindamycin and erythromycin was common. The isolation of diphtheroids from a properly obtained sputum sample from a patient with respiratory tract infection should not always be dismissed as due to contamination. The isolation, identification, and susceptibility testing of C. pseudodiphtheriticum from respiratory tract specimens may provide information useful for treatment of patients.

Clinical comparison of isolator and thiol broth with ESP aerobic and anaerobic bottles for recovery of pathogens from blood.

The recovery of pathogens and the speed of their detection were determined for our conventional blood culture system (an Isolator [Wampole] and a 100-ml Thiol bottle [Difco]) compared with automated ESP aerobic and anaerobic bottles (80 ml each; Difco). Each of the four culture devices was inoculated with approximately 10 ml of blood from symptomatic patients weighing more than 80 lb (ca. 36 kg). From 7,070 sets of cultures for 2,841 patients, 607 clinically significant isolates were recovered: 456 (75.1%) from the Isolator, 353 (58.2%) from Thiol, 377 (62.1%) from ESP aerobic bottles, and 346 (57.0%) from ESP anaerobic bottles. Of the 607 isolates, 149 (24.5%) were detected only with the conventional system (Isolator and/or Thiol), and 65 (10.7%) were detected only with the ESP two-bottle system (P < 0.001). Our conventional system allowed for detection of significantly more isolates of members of the family Enterobacteriaceae (P < 0.001), Staphylococcus aureus (P < 0.01), Staphylococcus spp. (coagulase-negative) (P < 0.01), and Enterococcus spp. (P < 0.05), and ESP facilitated detection of significantly more isolates of S. pneumoniae (P < 0.01). When all four devices in a culture set were positive for the same isolate, no microbial species or group was detected significantly earlier ( > or = 24 h) by either blood culture system. The Isolator contamination rate (4.8%) was > or = 6 times the rate for any of the bottles. Of pathogens detected by the Isolator, 50% were recovered in counts of < or = 1.0 CFU/ml and 18% were recovered only as a single colony. The ESP system offered an automated, less labor-intensive blood culture system for which routine subcultures were not required, but the important considerations of culturing large volumes of blood and of obtaining at least two sets from each patient in our population were reemphasized.

Efficacy of an enzyme-linked immunosorbent assay for detection of urinary tract immunoglobulins for diagnosis of urinary tract infections.

Results of the Uristat test (Shield Diagnostics Ltd.), a novel enzyme-linked immunosorbent assay (ELISA) for detection of urine antibodies to seven common bacterial pathogens, were compared with results of urine culture, urinalysis, and clinical history to determine the usefulness of Uristat in the diagnosis of urinary tract infections (UTIs). Midstream, catheterized, and indwelling catheter urine specimens sent to the laboratory for culture were included in the study. Quantitative cultures were performed on both 5% sheep blood agar and eosin-methylene blue agar. Uristat ELISAs were performed according to the manufacturer's instructions. By using a Bacillus subtilis bioassay technique, antibacterial activity was detected in the urine of 236 (22.2%) of 1,061 patients. Probable, possible, or asymptomatic UTIs were diagnosed for 258 (24.3%) of the 1,061 patients. Of those infections, 219 (84.9%) were caused by bacterial species whose antibodies were detectable by Uristat. Uristat's sensitivity and specificity were 76.7 and 56.0%, respectively. Uristat's predictive values of positive and negative results were 31.2 and 90.2%, respectively. Further development of the Uristat test is necessary before it can be of assistance in the diagnosis of UTIs.

Effects of itraconazole on mitogen stimulated human mononuclear leucocytes.

Lymphocyte transformation responses of unstimulated and mitogen-stimulated cells from normal subjects were measured in vitro in the presence of itraconazole, at therapeutic and at much higher concentrations. No differences in response from those of control cell cultures were detected at any concentration.

Saccharomyces cerevisiae fungemia in a multiply traumatized patient.

A case of Saccharomyces cerevisiae fungemia in a severely traumatized patient is described. This organism, although usually considered a nonpathogen, may occasionally cause serious illness in debilitated patients.

CNS toxicity associated with intraventricular injection of cefazolin. Report of three cases.

Three patients who experienced central nervous system toxicity secondary to intraventricular therapy with cefazolin are described. On the basis of this experience it is recommended that cefazolin not be used for intraventricular antibiotic therapy in the treatment of shunt infections.

Effects of quinolones on mitogen-stimulated human mononuclear leucocytes.

The effects of several quinolone compounds on mitogen-stimulation of normal human mononuclear leucocytes were studied. In these experiments, mononuclear leucocytes were obtained from heparinized whole blood of healthy young adult donors by Ficoll-hypaque sedimentation. The cells were cultured in the presence of both mitogen and various concentrations of the quinolone compounds. Control cultures (without the addition of the quinolones) were examined concurrently. Our data suggests that the quinolones tested, with the exception of rosoxacin (acrosoxacin) at a concentration of 2.5 mg/l, neither impair nor stimulate activation of lymphocytes by the mitogen phytohaemagglutinin (PHA) when used at the concentrations obtained during therapy.

Clinical relevance of culture versus screens for the detection of microbial pathogens in urine specimens.

The use of screens to detect "significant levels" of pathogenic microorganisms in urine specimens offers the advantages of both rapidly reporting results and controlling costs. Many of these screens, however, are insensitive at microbial counts below 10(5) colony-forming units (CFU)/ml of urine. It is increasingly apparent that patients with almost any type of urinary tract infection (except for most patients who are asymptomatic or who have pyelonephritis) may have urine concentrations of pathogens as low as 10(2) to 10(3) CFU/ml. This review documents factors that can contribute to diminished concentrations of microorganisms in urine, lists patient populations in whose urine microorganisms in concentrations well below 10(5) CFU/ml have been associated with infection, and makes recommendations for selection of laboratory tests, including rapid screens, for the diagnosis and management of urinary tract infections.

Detection of group A streptococci in the laboratory or physician's office. Culture vs antibody methods.

Much controversy has existed concerning the clinical significance of small numbers of group A streptococci (eg, one to ten or even 50 colonies) recovered in culture. The relative quantity of streptococci recovered is, in part, technique dependent. This review documents the need for sensitive throat culture technology, addresses technical problems associated with the culture procedure, and, in light of these problems, explores the need for very carefully performed studies on streptococcal antigen detection kits before their implementation as a routine test either in physicians' offices or in microbiology laboratories.

An outbreak of herpes simplex virus type I gingivostomatitis in a dental hygiene practice.

An outbreak of herpes simplex virus (HSV) type I gingivostomatitis occurred in a dental hygiene practice in November 1981. An epidemiologic investigation disclosed that 20 of 46 patients seen by the dental hygienist during a four-day period had this illness, whereas none of 26 patients seen by the dentist alone became ill. One day after the outbreak, the hygienist was found to have a herpetic whitlow. Identical endonuclease restriction enzyme type I HSV was isolated from the left index finger of the hygienist and from nine of 16 patients. The nine patients with positive cultures all had at least a fourfold increase in complement fixing antibody titer. A similar significant increase in titer indicated another seven cases.