Laboratory evaluation of urinary tract infections in an ambulatory clinic.

A 4-month evaluation of ambulatory patients with a suspicion of a urinary tract infection was performed. Specific objectives included assessment of five urinary screening methods, reevaluation of the necessity of the phenylethyl alcohol plate (PEA), and cost-effectiveness of screening for low colony count bacteriuria. Urine samples were collected as midstream, clean-caught specimens. A total of 142 samples, 87 from 79 symptomatic patients and 55 negative controls, were evaluated. All urine specimens were cultured using a 0.01 mL loop and a 0.001 mL loop onto Columbia sheep blood agar, MacConkey agar, and PEA agar. Twenty-four specimens (17%) were sterile, 64 (45%) were contaminated, and 54 (38%) were infected. Five urine screening methods were performed. These tests and their associated sensitivity and specificity are as follows. The Chemstrip 9 (Behring, Inc., Somerville, NJ) for leukocyte esterase and nitrate, 67%, 98%; microscopic analysis on spun urine, 79%, 93%; methylene blue stain for pyuria, 60%, 99%; Gram stain for pyuria, 45%, 93%; Gram stain for bacteriuria, 65%, 75%; and the URISCREEN (Analytab Products, Plainview, NY), 92%, 89%. Inclusion of a PEA plate for isolation of gram-positive organisms provided no additional information. Routine culture of urine samples at 10(-2) mL increased the contamination rate by 19%.

Comparative activity of cefepime, alone and in combination, against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients.

The comparative in vitro activity and synergy of cefepime were evaluated with clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients. The activity of cefepime, both alone and in combination, was comparable to those of other antibiotics. The clinical efficacy of cefepime in cystic fibrosis patients merits investigation.

In vitro activities of cefoperazone and sulbactam singly and in combination against cefoperazone-resistant members of the family Enterobacteriaceae and nonfermenters.

Among 28,000 isolates of the family Enterobacteriaceae and nonfermenters isolated at multiple medical centers, 1,084 (4%) were resistant to cefoperazone (MIC, greater than or equal to 64 micrograms/ml) and 1,711 (6%) exhibited cefoperazone MICs of 2 to 32 micrograms/ml. Ninety-six percent of these 2,795 isolates produced beta-lactamase, as determined by the nitrocefin test. Sulbactam alone (8 micrograms/ml) was inactive against 99.6% of the isolates other than Acinetobacter calcoaceticus and Pseudomonas cepacia. Sulbactam enhanced the activity of cefoperazone against 56% of the isolates of the family Enterobacteriaceae and 44% of the nonfermenters. In the presence of sulbactam concentrations of less than or equal to 8 micrograms/ml, 65% of the cefoperazone-resistant isolates had reductions in cefoperazone MICs of greater than or equal to 2 log2 dilution steps and were susceptible to less than or equal to 32 micrograms/ml. Antagonism was not observed.

In vitro activities of combinations of aztreonam, ciprofloxacin, and ceftazidime against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.

The in vitro activities of two-drug combinations of aztreonam, ciprofloxacin, and ceftazidime were studied in 96 clinical isolates of Pseudomonas aeruginosa and in 20 clinical isolates of Pseudomonas cepacia from cystic fibrosis patients. Some synergy was observed with each combination used against P. aeruginosa, but synergy was rare when the combinations were used against P. cepacia.

The frequency of bacterial pathogens in infections potentially preventable by antimicrobial prophylaxis.

Bacterial pathogen frequency was analyzed over a fourteen year period at the University of Utah Medical Center. Isolation techniques and identification procedures have remained essentially the same during this period, allowing for a valid comparison of this frequency. For most organisms the frequency of overall isolation had remained relatively stable. Differences were seen in the frequency of Pseudomonas aeruginosa and in the isolation rate of Staphylococcus aureus. Escherichia coli became proportionately less frequent, almost as an adjustment to the increase in Pseudomonas aeruginosa. A table is presented of these same pathogens and their likelihood to occur in post-operative patients categorized by surgery type in order to define their role in such infections potentially preventable by antimicrobial prophylaxis.

Evaluation of four newer antimicrobial agents in the Avantage susceptibility test system.

Antimicrobial elution disks containing amoxicillin-clavulanic acid (Augmentin), cefotetan, ciprofloxacin, or norfloxacin were tested in the Avantage automated susceptibility test system. Performance was compared against an agar diffusion procedure in a three-site collaborative study. Results of 1,500 comparison with amoxicillin-clavulanic acid showed a full accord (agreement of both systems) of 93.6% and an essential accord (agreement excluding minor discrepancies) of 97.6%. Results for cefotetan showed a full accord of 95.1% and an essential accord of 98.3% by the two methods. Results for both ciprofloxacin and norfloxacin were in full accord for more than 98% of tests with gram-negative bacilli and staphylococci, but tests with enterococci gave 38 and 26.1% minor discrepancies (the result of one method was resistant or susceptible and the result of the other method was intermediate), respectively. The results indicated that the Avantage test system is accurate and reliable and provides appropriate determination of bacterial susceptibility with the four antibiotics tested.

The use of aztreonam in the cystic fibrosis patient.

Eradication of pulmonary infection by Pseudomonas aeruginosa in cystic fibrosis (CF) patients has long presented a significant challenge to the medical community. Many antimicrobial agents have proved incompletely effective against this persistent pathogen, and even the aminoglycosides, which represent the traditional therapy for such infections, have been associated with considerable toxicity and resistance. The monobactam antibacterial agent aztreonam is used both as single-agent therapy and in combination with other drugs. Several controlled, clinical trials have demonstrated the efficacy of aztreonam in the treatment of CF patients with pulmonary exacerbations caused by P. aeruginosa. The only side effect of aztreonam therapy commonly encountered in these studies was elevation of hepatic transaminase concentrations; this effect was of uncertain significance. It was concluded that aztreonam may offer clinical efficacy comparable to that provided by the combination of tobramycin plus azlocillin. Further, there does not seem to be any appreciable difference in the development of resistance to aztreonam compared with traditional therapies.

Comparative in vitro activity of lomefloxacin (SC 47111 or NY-198) against fresh clinical bacterial isolates.

The in vitro antibacterial activity of a new difluorinated quinolone (lomefloxacin) was compared with that of ten selected antibiotics against 744 fresh bacterial isolates representing 32 species. Lomefloxacin was comparable to other quinolones tested against Enterobacteriaceae (MIC90, less than or equal to 0.25 micrograms/ml) and generally more effective than other compounds tested against Staphylococcus spp. and Pseudomonas aeruginosa with MIC90s of less than or equal to 2 and less than or equal to 4 micrograms/ml, respectively.

Changing susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis patients with the clinical use of newer antibiotics.

To detect a change in antibiotic susceptibility patterns in Pseudomonas aeruginosa isolates upon the introduction and clinical use of ciprofloxacin, aztreonam, and ceftazidime, MICs for clinical isolates collected before introduction of the antibiotics, during early clinical use, and later were determined for these and seven other antipseudomonal antibiotics. Concomitant resistance to two or more antibiotics was also studied. Over the three study periods, rates of susceptibility to 9 of the 10 antibiotics decreased. The largest decrease occurred with ceftazidime. Analysis of subsets of isolates from patients treated with ciprofloxacin or aztreonam also showed declining susceptibility to the latter but a stabilization of susceptibility to the former after an initial decline. Concomitant resistance within and among antibiotic classes was common.

The regionalization of laboratory services at the University of Utah Medical Center. Associated Regional and University Pathologists Inc (ARUP).

We feel that now, four years out, we have achieved the interim goals that we set for ourselves. There are some key aspects that we would do differently if we were now starting over, and we have provided that information to those seeking to begin similar off-site ventures who have sought our advice. There is an interesting constellation of factors that must be present for such an operation to succeed, and the individual components of that constellation will differ by institution and location. The rationale and circumstance will vary profoundly, and what is "right" in one setting may be entirely "wrong" in another. I feel compelled to caution the reader about the myriad of determinants and ingredients that must be considered. Study the precedents and seek knowledgeable advice from financial, legal, insurance, human resource (personnel), and laboratory management professionals. Regional laboratories can succeed. Hospitals may well benefit from a strategy of marketing services to physician staff members and the incremental financial and service benefits from added testing volume can be significant. However, the more expansive the business design, the more complicated the management requirements and demands and, potentially, the higher the risks, costs, pressures, and down-side factors. We feel very strongly about our focus of supporting the pathology and medical technology professions. Our value-added services are geared not only to providing technology, management, and financial services support for our clients, but also to not competing with them for local clientele. We have a program of teaching them how to market to that clientele and of providing the support materials to assist them in so doing. We have progressed from being a hospital laboratory to being a hospital laboratory referral laboratory, and now have also become a referral laboratory for other reference laboratories. As a full-service reference laboratory we send out very few tests, and are continually incorporating new tests and technologies. We have referral testing accounts currently in 42 states and we want to be the very best at what we do, namely, esoteric reference testing. Our credo is that quality at ARUP is making best continually better.

In vitro inactivation of aminoglycosides by cephalosporin antibiotics.

The in vitro inactivation of aminoglycoside antibiotics by semisynthetic penicillins complicates antibiotic assays. Due to the increasing number of new cephalosporins and use of aminoglycoside-cephalosporin combinations, we determined the in vitro stability of 28 aminoglycoside-cephalosporin combinations (gentamicin sulfate, tobramycin sulfate, netilmicin sulfate [10 micrograms/mL], and amikacin [20 micrograms/mL] in combination with cefazolin sodium, cefoxitin sodium, cefoperazone sodium, cefotaxime sodium, ceftazidime acid pentahydrate, cefsulodin sodium, or cefpiramide sodium at 100, 200, and 300 micrograms/mL). These mixtures were incubated at 37 degrees C and sampled at 0, 8, and 24 hours. Amikacin and tobramycin were most stable and netilmicin was the least stable of the aminoglycosides. Cefoxitin, ceftazidime, and cefotaxime were the least inactivating of the cephalosporins. When combined with first- and second-generation cephalosporins, aminoglycosides are relatively stable, but some laboratory precautions may be necessary when determining aminoglycoside levels in the presence of third-generation cephalosporin compounds.

Selective and differential medium for recovery of Pseudomonas cepacia from the respiratory tracts of patients with cystic fibrosis.

A selective and differential medium, OFPBL (oxidation-fermentation base supplemented with agar, lactose, and two antimicrobial agents), for the isolation of Pseudomonas cepacia from respiratory specimens of patients with cystic fibrosis was developed and tested. Among 725 specimens submitted from seven centers over a 4- to 6-month period, 58 (8%) yielded P. cepacia on OFPBL; only 19 of these were recovered on MacConkey or sheep blood agar (P less than 0.001). No isolate was recovered on MacConkey or sheep blood agar alone. Ranges of recovery rates among centers were 0 to 15% on OFPBL and 0 to 10% on MacConkey or sheep blood agar. Ninety percent of P. cepacia isolates were detected on OFPBL in less than or equal to 3 days. Other nonfermenters and yeasts isolated on OFPBL were distinguished from P. cepacia by failure to acidify the medium. The new medium was clearly superior to MacConkey and sheep blood agars for the isolation of P. cepacia from the respiratory secretions of patients with cystic fibrosis.

In vitro activity of aztreonam combined with tobramycin and gentamicin against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.

The in vitro activity of aztreonam combined with tobramycin and with gentamicin was assessed in 78 clinical isolates of Pseudomonas aeruginosa and 11 clinical isolates of Pseudomonas cepacia from patients with cystic fibrosis. Synergy was detected in 56.4% of P. aeruginosa isolates and 60% of P. cepacia isolates with the aztreonam-tobramycin combination and in 49.3% of P. aeruginosa isolates and 81.8% of P. cepacia isolates with the aztreonam-gentamicin combination. No antagonism was observed. These combinations merit clinical evaluation in the treatment of patients with cystic fibrosis.

Absence of rapidly developing resistance during treatment of cystic fibrosis patients with aztreonam.

The in vitro activity of aztreonam and 10 other antibiotics was determined for clinical isolates of Pseudomonas aeruginosa from 18 cystic fibrosis patients obtained before, at the end of, and 7-14 days after the completion of therapy with aztreonam. The percent of isolates susceptible to aztreonam at each sampling period were 79%, 78%, and 81% respectively.

In vitro activity in deptomycin (LY-146032) compared with other antimicrobial agents against gram-positive cocci.

A comparison was made of the activity of deptomycin (LY-146032) with that of ampicillin, cephalexin, cefamandole, cephalothin, erythromycin, teicoplanin, tetracycline, and vancomycin. The minimal inhibitory concentration (MICs) for greater than or equal to 90% of 356 Gram-positive cocci, against deptomycin, were less than or equal to 2 micrograms/ml. The MICs for the other antimicrobials varied greatly depending on the compound. A slight and unexplained inoculum effect was observed for LY-146032.

Ciprofloxacin versus tobramycin plus azlocillin in pulmonary exacerbations in adult patients with cystic fibrosis.

Twenty adult patients with cystic fibrosis who were experiencing acute pulmonary exacerbations were enrolled in a randomized, controlled trial comparing oral ciprofloxacin with intravenous tobramycin plus azlocillin. Efficacy of the two treatments was compared based upon changes in clinical status, pulmonary function tests, white blood cell counts, and quantitative bacteriology of sputum. No statistically significant differences were detected in these parameters of response between the two treatment groups (p greater than 0.05). Ciprofloxacin appears to be therapeutically equivalent to intravenous antibiotics in the treatment of adult patients with cystic fibrosis who are experiencing pulmonary exacerbations associated with susceptible bacteria.

Efficacy of aztreonam in pulmonary exacerbations of cystic fibrosis.

A noncomparative pilot study was conducted to assess the potential usefulness of aztreonam in pulmonary exacerbations of cystic fibrosis. Of 27 patients initially enrolled 25 received sufficient courses of aztreonam therapy to be evaluable. All patients received 200 mg/kg/day of aztreonam in 4 equally divided doses administered intravenously. Of 57 isolates of Pseudomonas aeruginosa from pretherapy sputum cultures, 48 were susceptible to aztreonam in vitro as were 11 of 18 strains isolated at the conclusion of therapy. With treatment colony counts of P. aeruginosa in sputum were reduced by 3 log10 or more in 15 patients. It was totally (but temporarily) eradicated in 11 of these patients. Clinical scores and white blood cell counts improved significantly (P less than 0.05). Side effects of aztreonam were limited to transient elevations of liver enzymes occurring in 16 patients. Aztreonam merits further evaluation in a randomized, comparative trial with standard antibiotic therapy for cystic fibrosis.