Lysis-centrifugation blood culture technique. Clinical impact in Staphylococcus aureus bacteremia.

To determine the clinical impact of enhanced detection of Staphylococcus aureus by a lysis-centrifugation (LC) blood culture system, consecutive cases of S aureus bacteremia during a seven-month period were reviewed. Of 77 clinically significant cases, the LC system detected 70 cases (91%) while a conventional broth system detected 67 cases (87%). Of 60 cases detected by both systems, the LC system was positive earlier than the broth system by one or more days in 34 cases (57%) and later in none. It also detected more (12 vs four of 13) patients with persistent bacteremia who were receiving antimicrobial treatment. Forty-three patients (56%) did not receive appropriate antimicrobial therapy until cultures were reported positive. Enhanced detection of S aureus bacteremia is a clinically important advantage of the LC blood culture technique.

Prospective randomized comparison of mezlocillin therapy alone with combined ampicillin and gentamicin therapy for patients with cholangitis.

Forty-six patients with cholangitis were randomized to receive therapy with mezlocillin sodium (24 patients) or a combination of ampicillin sodium--gentamicin sulfate (22 patients). The biliary concentration of mezlocillin was 112 times higher than that of ampicillin and 778 times higher than that of gentamicin. The ratio of the concentration in serum or bile over the minimum inhibitory concentration against aerobic gram-negative bacilli (therapeutic index) was higher for mezlocillin than for either ampicillin or gentamicin. Twenty (83%) of 24 patients were cured following mezlocillin therapy compared with 9 (41%) of 22 patients after ampicillin-gentamicin therapy. The 3 patients with superinfection were in the ampicillin-gentamicin arm of the study. Fewer toxic or adverse effects occurred in association with mezlocillin treatment than with ampicillin-gentamicin treatment. Mezlocillin therapy was more effective, less toxic, and less expensive than treatment with ampicillin and gentamicin for patients with cholangitis.

Treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis with ciprofloxacin or vancomycin alone or in combination with rifampin.

Therapy with vancomycin alone or ciprofloxacin alone did not significantly reduce the number of methicillin-resistant Staphylococcus aureus (MRSA) in bone in rats with experimental osteomyelitis, compared with the number in control rats. Treatment with rifampin significantly (p less than 0.01) decreased the number of MRSA per gram of bone compared with the number in control animals. There was no significant difference in the results of therapy with rifampin compared with the results obtained with the combination of vancomycin plus rifampin. The combination of ciprofloxacin plus rifampin was the most effective regimen for the treatment of MRSA experimental osteomyelitis and the results of therapy were significantly (p less than 0.01) superior to those following treatment with rifampin alone or the combination of vancomycin and rifampin. Following cessation of antimicrobial therapy, significant (p less than 0.01) regrowth of MRSA in bone occurred in animals treated with rifampin alone or ciprofloxacin plus rifampin. The emergence of resistance of MRSA during treatment occurred in two rats treated with rifampin alone and in one treated with rifampin plus vancomycin.

Antibiotic therapy for severe infections in infants and children.

In infants and children, the absorption, distribution, metabolism, and excretion of drugs may differ considerably in comparison with these factors in adults; consequently, differences exist in therapeutic efficacy and toxicity of various antibiotic agents. Because of known toxicity, certain drugs--such as chloramphenicol in high doses, the sulfonamides, and tetracycline--should not be used in neonates. Antibiotic therapy should be modified in neonates because of biologic immaturity of organs important for the termination of drug action. Because of poor conjugation, inactivation, or excretion, the serum concentrations of many antibiotics may be higher and more prolonged in neonates than in older infants; thus, lower doses and longer intervals between administration may be necessary. In this article, we suggest dosages of antimicrobial agents for severe infections in children, older infants, and neonates. Included in the discussion are the cephalosporins, especially the third-generation cephalosporins that have assumed an important role in empiric treatment of bacterial meningitis in pediatric patients because of their ability to penetrate the central nervous system and their effectiveness against beta-lactamase-positive and negative strains of Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis, and many gram-negative bacteria in the Enterobacteriaceae group. In patients with congenital or acquired immunodeficiencies, antifungal, antiviral, or anti-Pneumocystis agents are often added to the antimicrobial regimen for severe infections. We review the agents available for such treatment in children, the drugs used for childhood tuberculosis, and certain new antibiotics (aztreonam, ticarcillin-clavulanate, ciprofloxacin, and imipenem-cilastatin) that have proved useful in select cases but whose precise role in pediatric practice will necessitate additional clinical experience.

Leuconostoc bacteremia in an infant with short-gut syndrome: case report and literature review.

In this article, we report a case of Leuconostoc bacteremia in a 7-month-old infant who had short-gut syndrome after a gastroschisis repair and who was dependent on total parenteral nutrition through a central venous catheter. The organism was initially misidentified as viridans group streptococcus. Detection of vancomycin resistance led to the correct diagnosis of Leuconostoc species. The patient was successfully treated with ampicillin and an aminoglycoside. A review of the literature revealed prematurity, short-gut syndrome, prior vancomycin use, and central venous catheters as important predisposing factors. Leuconostoc species is an emerging pathogen that should be considered in the differential diagnosis of vancomycin-resistant gram-positive bacteremia, particularly in these clinical settings.

Antimicrobial therapy for infants and children: guidelines for the inpatient and outpatient practice of pediatriac infectious diseases.

In this article, we discuss antimicrobial regimens for both outpatient and inpatient use in infants and children. A substantial number of pediatric patient visits annually result in the prescribing of antimicrobial drugs. The emergence of bacteria resistant to commonly used antimicrobial agents is a growing concern. Information on newer drugs such as meropenem, which is active against penicillin-resistant Streptococcus pneumoniae and gram-negative bacilli, and cefepime, which has activity against gram-negative bacilli including Pseudomonas aeruginosa and against gram-positive cocci is also presented. Management of patients with congenital or acquired immunodeficiencies continues to be challenging in regard to the use of antimicrobial drugs to treat various fungal and viral infections. New formulations of older drugs such as aerosolized tobramycin and amphotericin B lipid complex are available. New antiviral agents have been approved, most of which are antiretroviral agents. Childhood tuberculosis is an ongoing concern, and regimens to treat Mycobacterium tuberculosis in children are discussed.

Ciprofloxacin versus trimethoprim-sulfamethoxazole: treatment of community-acquired urinary tract infections in a prospective, controlled, double-blind comparison.

In this study, we determined the safety and efficacy of the treatment of adults with urinary tract infection with ciprofloxacin hydrochloride (250 mg twice daily for 10 days) in comparison with trimethoprim-sulfamethoxazole (160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily for 10 days). Patients with signs and symptoms of urinary tract infection were randomized to receive ciprofloxacin (98 women and 5 men) or trimethoprim-sulfamethoxazole (92 women and 8 men). The success rate of therapy was 91% for both treatment arms of the study. Among seven failures after ciprofloxacin therapy, three were due to relapse of infection and two to side effects that necessitated a change in medication; in addition, two patients had persistent symptoms and required hospitalization. Among the six failures associated with trimethoprim-sulfamethoxazole therapy, four were due to relapse, one to persistence of infection, and one to a side effect that necessitated a change in medication. Among the patients treated with trimethoprim-sulfamethoxazole, 32% had mild or moderate adverse reactions; in comparison, 17% of the ciprofloxacin-treated patients had adverse reactions (P = 0.026). For the treatment of urinary tract infection in adult patients in this study, ciprofloxacin and trimethoprim-sulfamethoxazole were equally effective, but ciprofloxacin was associated with fewer adverse reactions.

Empiric therapy with moxalactam alone in patients with bacteremia.

Moxalactam was administered (20 mg/kg intravenously every 8 hours) as single-drug empiric antimicrobial therapy to 63 patients with bacteremia who were neither neutropenic nor immunosuppressed. Six patients (10%) had microorganisms that were susceptible to moxalactam and resistant to all other antimicrobial agents tested; two patients (3%) had microorganisms that were resistant to moxalactam and other agents tested. Of these 63 patients, 47 (75%) were cured with moxalactam therapy. Nine patients (14%) had breakthrough bacteremia while receiving other antimicrobial therapy and were cured subsequently with moxalactam therapy alone. The two major risk factors for failure of moxalactam therapy were polymicrobial bacteremia and an extrahepatic intra-abdominal source of infection; these two conditions frequently coexisted. Six of nine patients with polymicrobial bacteremia died. Superinfection (one pseudomonal, five enterococcal) was responsible for 6 of the 16 treatment failures. Enterococcal superinfection occurred exclusively among patients who had received relatively prolonged therapy with moxalactam for extrahepatic intra-abdominal infection, especially intraabdominal abscess. These five patients died, and postmortem examination showed that enterococcal superinfection was the major cause of death in all. Mild, reversible adverse reactions associated with use of moxalactam occurred in 14 of the 63 patients (22%). None had clinically overt bleeding. The use of moxalactam alone seems to be safe and effective and a cost-effective alternative empiric antimicrobial therapy for most patients with bacteremia who are not immunosuppressed or neutropenic and who are not at high risk of having Pseudomonas or polymicrobial bacteremia.

Yield of positive blood cultures in pediatric oncology patients by a new method of blood culture collection.

BACKGROUND: The optimal number of blood cultures and the volume of blood for pediatric blood cultures have not been defined. In 1990 such criteria were established at our institution. We retrospectively reviewed records of all pediatric oncology patients who were admitted for febrile episodes in 1989 and in 1991 and 1992 to determine whether there was an increase in the detection of bacteremia and fungemia. METHODS: Blood was drawn via venipuncture and central intravascular catheters and inoculated into the designated blood culture bottles. Each patient had a minimum of two separate blood draws, i.e. two separate cultures; the volume was determined by the patient's weight. In all cases < 1% of the patient's blood volume was drawn per culture. Patients' records were reviewed regarding type of malignancy, chemotherapy and neutropenia. RESULTS: The rate of bacteremic patients increased from 12% (13 of 113) in 1989 to 22% (27 of 123) in 1991. This increase continued through 1992 with 23% (27 of 118) of patients having positive blood cultures. Gram-positive bacteria predominated throughout the study period. CONCLUSIONS: Although factors such as more aggressive chemotherapy or a different spectrum of malignant diseases may contribute to the statistically significant increase in identification of bacteremic patients, a standardized method of blood culture collection is merited. The consistent volumes of blood per culture and the minimum of two cultures per febrile episode follow the principles of blood culture collection established for adults. The same principles should apply to pediatric patients.

Initial detection of bacteremia by subculture of unvented tryptic soy broth blood culture bottles.

Routine subculture of macroscopically negative blood cultures is a traditional blood culture procedure. The need to perform routine early (6-17 hr) and late (48 hr) subculture of unvented blood culture bottles when a simultaneous subculture of the vented bottle is performed has been questioned. Blood cultures in paired vented and unvented tryptic soy broth (TSB) bottles from 4574 patients were examined retrospectively. Subculture of unvented TSB bottles provided initial detection of 412 (5.0%) isolates from 277 (6.1%) patients and was comparable to that of vented TSB bottles for Pseudomonas and all other microorganisms, except for the Enterobacteriaceae (p less than 0.001; vented TSB), Candida (p less than 0.001; vented TSB), and Haemophilus influenzae (p less than 0.01; unvented TSB). Of the H. influenzae isolates, 46% were detected initially by subculture of the unvented TSB bottles; early subculture recovered 67% of these isolates. The value of subculture of unvented TSB bottles is minimized when subculture of the vented TSB bottle is routinely performed; however, routine subculture of the unvented bottle is recommended whenever TSB is used for detection of bacteremia in patients in whom H. influenzae infection is possible.

Pediatric bone and joint infections. Diagnosis and antimicrobial management.

Bone and joint infections in children provide unique clinical challenges. When evaluating children with suspected bone and joint infection, the differential diagnosis is broad. Consideration must be given to possible neoplastic and traumatic causes. Appropriate imaging and diagnostic techniques should be initiated without delay. Orthopedic consultation for surgical evaluation should be made early. Prolonged use of antibiotics is often warranted. Treatment often is continued in the outpatient setting, requiring frequent follow-up with appropriate serial laboratory studies to monitor side effects of antimicrobial agents.

Treatment of streptomycin-susceptible enterococcal experimental endocarditis with combinations of penicillin and low- or high-dose streptomycin.

We used two strains of streptomycin-susceptible enterococci (MIC, 64 and 128 micrograms of streptomycin per ml, respectively) isolated from patients with infective endocarditis. When combined with penicillin, 20 micrograms of streptomycin per ml killed both strains synergistically in vitro whereas combinations of 5 and 10 micrograms of streptomycin per ml did not act synergistically against either strain. By using the rabbit model of enterococcal experimental endocarditis, animals were treated for 3 days with procaine penicillin (1.2 X 10(6) U intramuscularly three times daily) together with low-dose streptomycin (3.5 mg/kg) or high-dose streptomycin (10 mg/kg) intramuscularly three times daily. The peak concentrations of streptomycin in serum at 0.5 h were 9.2 and 26.8 micrograms/ml in the low- or high-dose group, respectively. When combined with procaine penicillin, both dosages of streptomycin were more effective (P less than 0.01) than procaine penicillin alone for the treatment of enterococcal experimental endocarditis. There was no significant difference in the efficacy of procaine penicillin plus low-dose streptomycin versus procaine penicillin plus high-dose streptomycin therapy of enterococcal experimental endocarditis.

Early detection of positive blood cultures by the acridine orange staining technique.

Staining 2,205 macroscopically negative blood cultures with acridine orange after 6 to 17 h of inoculation and incubation was as sensitive as an early subculture in detecting positive blood cultures. Of the 179 positive blood cultures, 30 (16.8%) were detected by acridine orange alone, 19 (10.6%) were detected by early subculture alone, 84 (46.9%) were detected by both techniques, and 46 (25.7%) were not detected by either method. The latter group includes cultures that became positive after 48 h of incubation. Acridine orange staining of smears prepared from macroscopically negative blood cultures after 6 to 17 h is a rapid, reliable method to detect positive blood cultures.

Comparison of the Roche Septi-Chek blood culture bottle with a brain heart infusion biphasic medium bottle and with a tryptic soy broth bottle.

In a comparison of 1,368 positive blood cultures, a vented Roche Septi-Chek (V-RSC) blood culture bottle was superior to an unvented tryptic soy broth-containing bottle (Difco) for the recovery of all aerobic and facultatively anaerobic microorganisms. Anaerobic bacteria were recovered more frequently and earlier in the unvented tryptic soy broth-containing bottle. A separate comparison of 529 positive blood cultures was conducted to examine the performance of the V-RSC bottle with that of a vented brain heart infusion biphasic medium. The V-RSC bottle recovered significantly more isolates of Enterobacteriaceae and of anaerobic bacteria than did the vented brain heart infusion biphasic medium. The V-RSC bottle is a reliable blood culture system for all aerobic and facultatively anaerobic microorganisms. Because of its suboptimal recovery of anaerobic bacteria, it is recommended that the V-RSC bottle be used in combination with an unvented vacuum blood culture bottle.

Relative efficacies of broad-spectrum cephalosporins for treatment of methicillin-susceptible Staphylococcus aureus experimental infective endocarditis.

The effects of treatment with broad-spectrum parenterally administered cephalosporins and cefuroxime, cefazolin, or nafcillin were compared in an experimental model of Staphylococcus aureus infective endocarditis, and the results in vivo were compared with the activities of the study drugs in vitro. After 3 days of treatment, all antimicrobial agents tested were more effective than no treatment in reducing the number of surviving bacteria in cardiac valve vegetations. Nafcillin was the most effective agent studied and was significantly more active than was ceftizoxime, ceftriaxone, cefotaxime, cefoperazone, cefuroxime, or cefazolin (P < or = 0.05). Cefpirome and ceftazidime were the most effective broad-spectrum cephalosporins. The outcome of treatment with cefpirome or ceftazidime was similar to that of treatment with nafcillin and significantly better than that of treatment with ceftizoxime or cefotaxime (P < or = 0.05). Treatment outcome correlated closely with the MICs of the antimicrobial agents for the study strain with the exception of ceftazidime, which was significantly more active in vivo in comparison with other agents than predicted by its MIC (P < or = 0.0003). When ceftazidime was excluded as an outlier, treatment outcome correlated with the MICs of the remaining study drugs (Spearman's correlation coefficient, 0.95; P < or = 0.0004), as well as with the estimated percentage of time during which the concentration of total drug (correlation coefficient, -0.85; P < or = 0.007) or free drug (correlation coefficient, -0.90; P < or = 0.003) exceeded the MIC. A consideration of total or free drug concentrations in relation to MICs did not significantly improve the correlation with outcome observed with the MICs alone.

In vitro and in vivo studies of streptomycin-resistant, penicillin-susceptible streptococci from patients with infective endocarditis.

The combination of penicillin and streptomycin did not act synergistically in vitro against three streptomycin-resistant strains (MIC, greater than or equal to 1,000 micrograms of streptomycin/ml) of penicillin-susceptible streptococci. Using a model of experimental infective endocarditis, we infected rabbits with a control streptomycin-susceptible strain, with an intermediately streptomycin-resistant strain (MIC, 1,000 micrograms/ml), and with a highly streptomycin-resistant strain (MIC, greater than 32,000 micrograms/ml). Treating animals with a combination of procaine penicillin and streptomycin was more effective (P less than .01) than treating them with procaine penicillin alone only for those animals infected with the control streptomycin-susceptible strain. Treatment with procaine penicillin plus gentamicin was more effective (P less than .01) than treatment with procaine penicillin alone for all three treatment groups and was more effective (P less than .01) than treatment with procaine penicillin and streptomycin for those animals infected with an intermediately or highly streptomycin-resistant strain of streptococci.

In vitro and in vivo activity of ciprofloxacin against enterococci isolated from patients with infective endocarditis.

In vitro activity of ciprofloxacin against 27 strains of enterococci was inoculum dependent. Using inocula of 10(5) to 10(6) or 10(7) to 10(8) CFU of enterococci per ml, the MICs for 50 and 90% of strains tested increased from 1 to greater than or equal to 128 micrograms of ciprofloxacin per ml with the higher inoculum compared with the lower inoculum. The MBC for 50% of strains tested increased from 2 to greater than 128 micrograms/ml and the MBC for 90% of strains tested increased from 8 to greater than 128 micrograms of ciprofloxacin per ml with the lower and higher inocula, respectively. The combination of penicillin-gentamicin was more effective in vitro than the combination of ciprofloxacin-gentamicin against the low or high inoculum of enterococci. Using two strains of enterococci, we studied the efficacy of ciprofloxacin in the treatment of enterococcal experimental endocarditis in rabbits. Ciprofloxacin used alone or combined with gentamicin was significantly less effective (P less than 0.01) than procaine penicillin alone or procaine penicillin combined with gentamicin for the treatment of enterococcal experimental endocarditis. The combination of ciprofloxacin-procaine penicillin was not a more effective therapy than procaine penicillin alone.

Comparison of ciprofloxacin and co-trimoxazole in the treatment of uncomplicated urinary tract infection in women.

Sixty-five women with uncomplicated urinary tract infection were evaluated in a prospective, randomized, double blind study comparing ciprofloxacin (250 mg twice daily for ten days) with co-trimoxazole (160 mg trimethoprim and 800 mg sulphamethoxazole twice daily for ten days). Results were analysed with respect to eradication of the urinary tract pathogen, resolution of clinical symptoms, incidence of relapse, and incidence of adverse effects. Among the 31 women who received ciprofloxacin, there was eradication of the micro-organism and complete resolution of clinical symptoms in 100% five to nine days after completion of therapy. Among the 34 patients who received co-trimoxazole, there was eradication in 94% and clinical resolution in 91%. Of the ciprofloxacin-treated women 6.5% (2/31) relapsed compared with 18% (6/34) of co-trimoxazole-treated women. Overall cure rates for 65 patients were 93.5% and 82.3% for ciprofloxacin and co-trimoxazole (difference not statistically significant), respectively. A statistically significant (P less than 0.05) increase in adverse side effects was noted in patients treated with co-trimoxazole. Based upon preliminary data it appears that ciprofloxacin is as effective and less toxic than co-trimoxazole for treatment of uncomplicated urinary tract infection in women.

Activity of penicillin combined with an aminoglycoside against group B streptococci in vitro and in experimental endocarditis.

Group B streptococci were less susceptible in vitro to penicillin and to aminoglycosides with an inoculum size of 10(7)-10(8) cfu/ml than with an inoculum size of 5.5 X 10(5)-10(6) cfu/ml. With a rabbit model of experimental group B streptococcal endocarditis, after one or three days of therapy with procaine penicillin alone, the mean log10 cfu/g of valve vegetation was significantly lower (P less than 0.01) than that of the control groups. After one day of therapy, procaine penicillin combined with streptomycin was significantly more effective (P less than 0.01) than was treatment with procaine penicillin alone. There was no significant difference (P greater than 0.05) in the results of treatment of animals for one day with procaine penicillin combined with streptomycin compared with those of animals treated for three days with procaine penicillin alone.

Antimicrobial therapy of experimental endocarditis caused by nutritionally variant viridans group streptococci.

Rabbits with nutritionally variant viridans group streptococcal experimental endocarditis were treated three times daily for 3 days with procaine penicillin (1.2 X 10(6) U) alone or together with low-dose streptomycin (2 mg/kg), high-dose streptomycin (8 mg/kg), low-dose gentamicin (0.32 mg/kg), or high-dose gentamicin (1.05 mg/kg). The mean 0.5-h serum concentrations of streptomycin were 5.3 and 22.5 micrograms/ml in the low- and high-dose group, respectively, and the concentrations of gentamicin were 0.7 and 2.5 micrograms in the low- and high-dose groups, respectively. The combination of procaine penicillin with each dose of aminoglycoside was significantly more effective (P less than 0.001) than was procaine penicillin alone. In combination with procaine penicillin, the higher dose of streptomycin was significantly more effective (P less than 0.02) than the lower dose of streptomycin. The higher dose of streptomycin was not significantly more effective than either dose of gentamicin. The results of treatment with the high or low dose of gentamicin were virtually identical.