A multicenter comparative trial of tobramycin and ticarcillin vs moxalactam and ticarcillin in febrile neutropenic patients.

During a multicenter prospective randomized trial in febrile neutropenic patients (neutrophil count, less than 1,000/cu mm), 103 episodes were treated with tobramycin sulfate plus ticarcillin disodium (TT) while 117 were treated with moxalactam plus ticarcillin disodium (MT). The majority of patients had an underlying diagnosis of leukemia (60%) and most (62.8%) had granulocyte counts of less than 100/cu mm at the start of therapy. The response rates for clinically or microbiologically documented episodes were 38 of 60 (55.1%) for TT and 38 of 64 (59.4%) for MT. The MT regimen appeared to be more effective for gram-positive infections (56% vs 33%) while TT appeared more effective for gram-negative infections (64% vs 40%). Nephrotoxicity attributable to study drugs occurred in only 2.3% of cases (one on each treatment arm). Prolongation of the prothrombin time was observed in only six of 78 (7.7%) in the TT arm as compared with 39 of 103 (38%) in the MT arm. Neither regimen was adequate for the unusually high frequency of gram-positive pathogens seen during this study.

Control of construction-associated nosocomial aspergillosis in an antiquated hematology unit.

OBJECTIVE: To determine the incidence of aspergillosis in patients with leukemia or bone marrow transplants during a construction-associated outbreak, and the effect of an environmental control program for Aspergillus. DESIGN: Clinical, microbiological, and pathological records were reviewed retrospectively once the outbreak was appreciated, and prospectively thereafter, to determine the presence or absence of aspergillosis and duration of neutropenia. SETTING: A university tertiary-care center with a single designated hematology-oncology unit. PATIENTS: From January 1988 to September 1993, there were 141 patients with leukemia or bone marrow transplants identified as being neutropenic during 231 admissions to this specialized unit. INTERVENTIONS: Installation of wall-mounted portable high-efficiency particulate air (HEPA)-filter air purifiers, application of copper-8-quinolinolate-formulated paint, replacement of perforated ceiling tiles with nonperforated type, sealing of all windows, replacement of horizontal, dust-accumulating blinds with vinyl, opaque, roller shades, and systematic and regular cleaning of surfaces. RESULTS: Thirty-six cases of nosocomial aspergillosis were diagnosed during this period. The incidence density (ID) in the preconstruction period was 3.18 per 1,000 days at risk. During construction activity-before the implementation of a control strategy-the ID increased dramatically to 9.88 per 1,000 days at risk. With infection control measures implemented and continued construction work, the ID decreased to 2.91 per 1,000 days at risk, comparable to the preconstruction baseline rate. CONCLUSIONS: An environmental control strategy incorporating widely available technology may have played an important role in controlling this outbreak of construction-associated invasive aspergillosis.

An outbreak of Serratia marcescens infections related to contaminated chlorhexidine.

An outbreak of Serratia marcescens infections occurred in a university tertiary-care hospital. Alcohol-free chlorhexidine solutions were contaminated with S marcescens. The majority of patient and chlorhexidine strains had similar pulsed field-gel electrophoresis banding patterns. Chlorhexidine was recalled, and the rate of S marcescens isolation returned to baseline. Chlorhexidine without alcohol should not be used as an antiseptic.

Strategies for molecular characterisation of methicillin- and gentamicin-resistant Staphylococcus aureus in a Canadian nosocomial outbreak.

Sixteen methicillin-resistant Staphylococcus aureus (MRSA) isolates, from a single nosocomial outbreak, were tested for molecular and phenotypic relationships. Two of the 16 outbreak strains were gentamicin resistant (Gmr) and the plasmids that they carried were characterised by reverse field electrophoresis, restriction endonuclease analysis and gene hybridisation. The gentamicin-resistant (Gmr) strains harboured two plasmids, a Gmr plasmid of 36.5 kb and a cryptic plasmid of 25.4 kb, whereas the other 14 isolates contained only the cryptic plasmid. Gentamicin resistance was encoded by a 2.5-kb HindIII fragment of the 32.8-kb plasmid and is similar to the 2.5-kb HindIII fragment also described for S. aureus Gmr plasmids from Australia and the USA. The Gmr plasmid was non-conjugal and was cured by ethidium bromide at a frequency of 4%. Two MRSA strains isolated subsequently from the same hospital were also Gmr and had identical plasmid and restriction endonuclease profiles to the two Gmr strains studied initially. Two other S. aureus isolates from the original carrier detected in this study and from his son were methicillin and gentamicin susceptible and had novel profiles. Since large plasmids show anomalous migration in agarose gels, more definitive analyses than simple plasmid identification should be considered when studying nosocomial outbreaks.

Activity of vancomycin, teicoplanin and cephalosporins against penicillin-susceptible and penicillin-intermediate Streptococcus pneumoniae.

OBJECTIVE: To report in vitro susceptibilities of penicillin-susceptible and penicillin-intermediate Streptococcus pneumoniae isolates to cephalosporins, vancomycin and teicoplanin. DESIGN: Minimal inhibitory concentrations (mic) were determined according to National Committee for Clinical Laboratory Standards guidelines for 17 penicillin-susceptible isolates (mic 0.06 mg/L or less) and 16 isolates showing intermediate susceptibility to penicillin (mic 0.12 to 1.0 mg/L). SETTING: Tertiary care university centre. MAIN RESULTS: Comparison of the mic(90) values with those of other antibiotics tested demonstrated that ceftriaxone, cefotaxime and teicoplanin were the most active agents against penicillin-susceptible strains. However, teicoplanin had the lowest mic and was superior to other agents against strains with intermediate penicillin susceptibility. The mics of all cephalosporins increased in concordance with the mic of penicillin. CONCLUSION: Isolates demonstrating intermediate susceptibility or resistance to penicillin should be routinely evaluated for susceptibility to clinically important cephalosporins.

Reduction in clinical response to empiric antimicrobial therapy of febrile granulocytopenic patients receiving TMP/SMX infection prophylaxis.

In the course of a multicentre clinical trial evaluating two antibacterial regimens for the empiric treatment of suspected infection in febrile neutropenic cancer patients, a suboptimal response was noted among recipients of antibacterial prophylaxis with trimethoprim/sulphamethoxazole (TMP/SMX). Multivariate analysis identified TMP/SMX prophylaxis as a predictor of poor outcome independent of other variables such as classification of infection, marrow recovery, neutrophil count at first fever, indwelling central venous catheter use, and underlying disease. This effect appeared to be restricted to recipients of tobramycin plus ticarcillin (TT). TMP/SMX suppresses potentially pathogenic aerobic Gram-negative bacilli and allows colonization and subsequent infection by Gram-positive microorganisms against which TT-like regimens have limited activity. Recognition of this phenomenon may permit a more appropriate selection of antibacterial agents for the therapy of suspected infection in the neutropenic patient.

Epidemiologic and clinical features of sporadic Salmonella enteric fever.

Twenty-seven cases of enteric fever were diagnosed between January 1961 and February 1977 at a medium-sized urban hospital. Nineteen of the patients had recently travelled abroad. Fever was the only constant finding, and four patients noted fever and headache as their only symptoms. Splenomegaly was present in 30% and rose spots in just 11%. Enteric fever was initially suspected in only 63% of cases, and a mean of 4.8 days elapsed after admission before specific therapy was instituted. Salmonella was cultured from blood samples in 19 of 24 patients and from stool specimens in 21 of 27, but was never isolated from the urine. Serum O agglutinins, while eventually present in 54% of the patients tested, did not help in establishing an early diagnosis. No deaths occurred, though two patients sustained relapses. Sporadic enteric fever is unlikely to be suspected unless associated with recent foreign travel, but is easily diagnosed by usual culture methods.

Cerebrospinal fluid penetration of amikacin.

Adult volunteers underwent a single lumbar puncture 1 to 8.5 h after one 7.5-mg/kg intramuscular amikacin injection. Eighteen showed no detectable drug in cerebrospinal fluid; six had concentrations <0.5 mug/ml.

Comparison of the Gram-stained urethral smear and first-voided urine sediment in the diagnosis of nongonococcal urethritis.

The diagnostic sensitivity of the numbers of leukocytes in the sediment of first-voided urine and in gram-stained smears of urethral secretions was evaluated by a study of 62 men with symptoms of nongonococcal urethritis. Fifty-one patients (82.3%) had pyuria (defined as ten or more leukocytes per high-power field) in the sediment of first-voided urine, whereas 8 (45.2%) had more than four leukocytes per oil-immersion held in gram-stained urethral smears. Frequencies of positive first-voided urine sediments and urethral smears were similar in Chlamydia trachomatis--positive and -negative cases. Results of cultures, urinalyses, and urethral smears were not affected by recent micturition. Pyuria in the first-voided urine but not a positive urethral smear is a sensitive sign of urethritis whether or not urethral discharge is evident. Specimens of urethral secretions were subjected to different storage conditions to determine the effect on subsequent isolation of C. trachomatis. Equal rates of isolation were demonstrated for specimens that had been held at 4 degrees C for either four or 20-24 hr or frozen to -70 degrees C for one week prior to culture.

Cerebrospinal fluid penicillin levels during therapy for latent syphilis.

Cerebrospinal fluid and serum penicillin levels were determined in patients with latent syphilis. Mean serum concentration one week after the third weekly dose of 2.4 million units penicillin G benzathine was 0.32 units/mL. Concurrent administration of probenecid orally produced a mean serum penicillin level of 0.41 units/mL. Doubled penicillin doses without and with daily orally administered probenecid resulted in mean serum concentrations of 0.75 and 1.00 units/mL, respectively. Two of six patients in the last group had CSF penicillin concentrations greater than 0.03 units/mL.

Treatment of pneumonia and other serious bacterial infections with cephapirin.

Nineteen patients with pneumonia due to Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, or Escherichia coli were treated with 4 to 18 g of cephapirin daily. There were three treatment failures. One patient each with pneumonia due to E. coli or S. pneumoniae died despite apparent eradication of the pathogen. Lobar pneumonia due to K. pneumoniae progressed during therapy in a third patient to lung gangrene, necessitating pneumonectomy. Five additional patients with pneumococcal pericarditis or septic bursitis, empyema, cannula-associated bacteremia, and thoractomy wound infection due to S. aureus were cured. All isolates of S. aureus, S. pneumoniae, and group A Streptococcus were inhibited by 0.8 mug of cephapirin per ml; minimal inhibitory concentrations of cephalothin were similar. Ninety percent of K. pneumoniae, 85% of Proteus mirabilis, 73% of E. coli, and 30% of Enterobacter were inhibited by 12.5 mug cephapirin per ml. All isolates of Pseudomonas, Serratia and indole-positive Proteus had a cephapirin minimal inhibitory concentration of [Formula: see text] 100 mug/mg. Serum concentrations after intravenous and intramuscular injection were similar to those reported for cephalothin. The intramuscular injections were moderately painful, and intravenous infusions caused phlebitis in three of nine patients treated with doses up to 18 g per day. Cephapirin appears comparable to cephalothin in vitro and is an effective agent in treatment of infection due to S. aureus and S. pneumoniae.

Single-dose treatment of gonococcal urethritis in males: evaluation of procaine penicillin, ampicillin and spectinomycin.

Males with acute gonococcal urethritis were treated at random with 2.4 million units aqueous procaine penicillin G intramuscularly plus 1.0 g. probenecid orally, 3.5 g. ampicillin orally plus 1.0 g. probenecid orally, or 2.0 g. spectinomycin intramuscularly. The overall follow-up was 97%. All treatments were of equal efficacy, eradication of gonococcal disease being observed in 93 to 97% of treated patients. Treatment failures occurred in each drug group and pre-treatment isolates recovered from these cases showed decreased susceptibility to the agent used. Aqueous procaine penicillin G plus probenecid remains the preferred therapy for gonorrhea. For patients hypersensitive to penicillin, spectinomycin is currently a reasonable alternative drug. This agent, unlike procaine penicillin-probenecid, is probably ineffective against concurrent incubating syphilis, and future development of bacterial resistance is a definite possibility.

Comparison of amoxicillin and ampicillin in single-dose oral treatment of males with gonococcal urethritis.

Amoxicillin in single oral doses of 2.0 g, 2.0 g plus 1.0 g probenecid, or 3.0 g was compared with ampicillin 3.5 g plus 1.0 g probenecid in the treatment of 203 males with uncomplicated acute gonococcal urethritis. Cure rates above 95% were produced by all treatments except the 2.0-g amoxicillin dose, which cured 89% of patients. Of 198 pretreatment gonococcus isolates tested by an agar dilution technique for susceptibility to penicillin G, ampicillin and amoxicillin, over 50% showed relative resistance (MIC > 0.06 mug/ml) to the antibiotics. However, amoxicillin was somewhat more active against isolates showing considerable resistance (MIC >/= 1.0 mug/ml) to penicillin G or ampicillin. Adverse effects of amoxicillin were few: two patients reported transient nausea and six noted short-lived diarrhea. No hypersensitivity reactions were observed.

Susceptibility of the Bacteroides fragilis group to newer quinolones and other standard anti-anaerobic agents.

The susceptibilities of 200 clinical isolates of the Bacteroides fragilis group to four quinolones (moxifloxacin, clinafloxacin, trovafloxacin and ciprofloxacin) were determined, as well as to cefoxitin, clindamycin, metronidazole, imipenem and ticarcillin-clavulanic acid. The results for the latter five agents were compared with those of a study on 200 isolates done 6 years previously. Clinafloxacin and trovafloxacin were the most active agents tested with MIC90s lower than all other antimicrobials except imipenem. Susceptibility rates for imipenem, ticarcillin- clavulanic and metronidazole continue to be high, although resistant strains are emerging. For ticarcillin-clavulanic acid and metronidazole, MIC90s increased four- to eight-fold for the B. fragilis species between the two study periods.

Chlamydia trachomatis genital infections.

The prevalence and clinical features of Chlamydia trachomatis infection were studied in men with nongonococcal urethritis (NGU), in their female sexual partners, and in other women. Of 92 patients with NGU, 36 (39%) were chlamydia-positive; although all had symptoms of urethritis, fewer than half had evident discharge. Clinical features of chlamydia-positive and chlamydia-negative NGU were indistinguishable. Most female contacts of chlamydia-positive patients with NGU were infected with C. trachomatis; contacts of chlamydia-negative patients with NGU seldom harboured chlamydia. Inflammatory and erosive changes were equally common in the uterine cervix of chlamydia-positive and chlamydia-negative women, although almost half of infected cases had no clinical signs of infection and no specific symptoms. In such women the present unavailability of sensitive screening techniques is a major obstacle to the effective control of chlamydial infection.

Comparative activity of netilmicin, gentamicin, amikacin, and tobramycin against Pseudomonas aeruginosa and Enterobacteriaceae.

Netilmicin (Sch 20569), a semisynthetic aminoglycoside antibiotic, was compared with gentamicin, tobramycin, and amikacin against 242 clinical isolates of Pseudomonas and Enterobacteriaceae. The minimum inhibitory concentration (MIC) was determined in both solid and liquid media. Netilmicin exhibited typical aminoglycoside properties, such as little effect of inoculum size on MIC, relatively small gap between MIC and minimum bactericidal concentration, and potentiation of anti-Pseudomonas activity in the presence of carbenicillin. Netilmicin provided no advantage in antimicrobial activity over gentamicin for either Pseudomonas or Enterobacteriaceae. Nearly complete cross-resistance to netilmicin was encountered with isolates resistant to gentamicin in either solid or liquid media. Netilmicin was less active than gentamicin against isolates of Pseudomonas and Providencia. Major discrepancies between MIC values determined in agar as opposed to those determined in broth were encountered for most isolates of Pseudomonas but also, depending upon antibiotic tested, for between 15 and 40% of isolates of Enterobacteriaceae. This new aminoglycoside agent will be useful clinically only if it is shown to be significantly less toxic than presently available analogues.

Synergistic activity of carbenicillin and gentamicin in experimental Pseudomonas bacteremia in neutropenic rats.

Rats made neutropenic with cyclophosphamide were infected intraperitoneally with Pseudomonas aeruginosa. The challenge organism was killed synergistically in vitro by the combination of gentamicin and carbenicillin. Untreated neutropenic rats infected with 3 x 10(6)Pseudomonas died between days 2 and 7, and the overall mortality was 70%. Groups of infected neutropenic rats were treated intramuscularly with 1.5 or 6 mg of gentamicin per kg per dose, 100 or 400 mg of carbenicillin per kg per dose, or 1.5 mg of gentamicin and 100 mg of carbenicillin per kg per dose. Treatment was begun at 2 h postinfection and was continued every 8 h for about 72 h. Cultures of blood and peritoneal washings were performed in control and treated rats at 1, 4, 24, 48, and 72 h postinfection. Gentamicin at either dose level was ineffective in preventing death, but mortality was significantly reduced by high-dose carbenicillin and low-dose combination therapy. In addition, the latter regimens sterilized the peritoneal fluid and blood. Carbenicillin and gentamicin showed in vivo synergy in the treatment of neutropenic Pseudomonas-infected rats.

Patients' compliance with follow-up after treatment of gonococcal urethritis.

By means of telephone tracing 96% follow-up was achieved in men treated for gonococcal urethritis. A large proportion (34.8%) of patients required one or more calls before follow-up could be obtained. Frequency of sexual re-exposure, proportion with persistent gonorrhea or reinfection, and interval between initial therapy and follow-up were greater in those who required telephone contact for follow-up than in the group who returned for follow-up. Failure to reappear for follow-up does not imply either bacteriologic cure or disappearance of symptoms. Control of gonococcal infection still depends largely upon aggressive methods of case finding, appropriate therapy and careful follow-up.