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PubMed1990

Chemoprophylaxis of gram-negative infections in neutropenic patients.

Gram-negative infections in neutropenic patients originate frequently from the gut flora. Attempts to decrease the incidence of these infections have utilized several regimens for gastrointestinal decontamination, of which some have proven to be clinically useful. Orally administered nonabsorbable antibiotics (aminoglycosides, polymyxins) can decrease the incidence of gram-negative sepsis during neutropenia, but, with the possible exception of netilmicin, tolerance to these agents is generally poor, and compliance is low. Trimethoprim-sulfamethoxazole has been used widely for the prophylaxis of infections in neutropenic patients. Clinical results with this agent have been conflicting, as its efficacy is clearly related to epidemiological patterns of resistance of the pathogens in the population under study. More recently, the quinolones, which are well tolerated by patients and are presently active on most strains of Enterobacteriaceae, have been associated with a virtual eradication of gram-negative infections in neutropenic patients. These results have been paralleled by an increase in the frequency of gram-positive infections, which, fortunately, cause an incidence of mortality that is much lower than that seen in gram-negative sepsis. The fact that the quinolones are absorbed systemically might help to explain their efficacy in chemoprophylaxis during neutropenia. This paper discusses the chemoprophylaxis of gram-negative infection during neutropenia in the light of theoretical concepts such as 'colonization resistance', 'selective decontamination', and 'bacterial translocation'.

Agranulocytosis↗
PubMed1989

Treatment of AIDS-associated heart disease.

Although the diagnosis of AIDS-associated heart disease is becoming routine, its treatment has not been reported except in anecdote. Also, it has been unclear whether the odds of successful treatment are altered because of the presence of cardiac involvement per se. This communication reports the authors' treatment of 18 patients with AIDS-associated heart disease. Their results are combined with the treatment results of all patients reported in the literature to date with AIDS-associated heart disease. Treatment success, defined as eradication of the organism and no relapse, was achieved in their patients with M. tuberculosis (M. tb), cardiac cryptococcosis, and Salmonella typhimurium. M. tb required emergency pericardiectomy (well tolerated in all patients), then administration of rifampin, isoniazid, and ethambutol. Cryptococcosis was treated acutely with amphotericin B and flucytosine, then with maintenance amphotericin B. The response, which included resolution of congestive heart failure, occurred within a week. Salmonella endocarditis was cured with administration of ampicillin and netilmicin for one month. When the patients' data were combined with those of patients from the literature, the authors found that the odds of successful treatment for tuberculous pericarditis were somewhat lower than if the tuberculosis was extracardiac (50% vs 67%). With cryptococcal heart disease, the odds of successful treatment were actually significantly better than when only extracardiac disease was present. The authors conclude that infectious forms of AIDS-associated heart disease are often treatable. Although some cardiac infections are less likely to respond to treatment if there is cardiac involvement, mostly the response to treatment is similar to the response with only extracardiac involvement.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Fungal peritonitis in children on continuous ambulatory peritoneal dialysis.

Between 1979 and 1985, six of 26 patients undergoing continuous ambulatory peritoneal dialysis developed fungal peritonitis. All had received antibacterial therapy with cefamandole and/or netilmicin prior to the diagnosis. The causal organisms were Candida albicans (three), Candida glabrata (one), Cryptococcus laurentii (one) and Saccharomyces cerevisiae (one). Treatment comprised catheter removal preceded by antifungal drugs (flucytosine and/or amphotericin B) in four patients and catheter removal alone in two. All patients were transferred to haemodialysis and five of the six developed extensive intra-abdominal adhesions. The most prudent management of fungal peritonitis in children would seem to be early cannula removal.

Adolescent↗
PubMed1981

Aminoglycoside predictions using a hand-held calculator: limitations of the model.

Previously published methods for determining an appropriate aminoglycoside dosage have been adapted for use in the hand-held programmable calculator (Texas Instrument-59). The purpose of this study was to evaluate the accuracy of calculator-generated serum level predictions compared with measured values. Twenty-four adult patients receiving intravenous aminoglycosides (gentamicin, netilmicin, or tobramycin) had urine and serum collected for creatinine clearance calculations and had blood obtained for peak and through aminoglycoside concentration determinations. All but one patient had normal renal function. A statistically significant relationship between predicated and measured creatinine clearance values was found. There was also generally good agreement between the calculator-predicted aminoglycoside levels and the measured levels, although some patients exhibited unexplained deviations. Error in the estimation of creatinine clearance and adjustments for lean body weight did not improve prediction accuracy. We conclude that the hand-held calculator was able to predict measured aminoglycoside levels for most patients with acceptable precision. However, the calculator method offers no real advantage over other methods (except speed in performing the calculation), and may give the user a false sense of security.

Aminoglycosides↗
PubMed1991

Use of restricted antibiotics in primary care.

The objective of this study was to detect and evaluate the use of restricted antibiotics (RAs) in our ambulatory care site. We retrospectively analyzed 1084 treatments of a selected group of intramuscularly administered antibiotics that are usually considered restricted for use in hospitals. Five cephalosporins, four aminoglycosides, and one acylureidopenicillin were analyzed. The study was conducted in 47 primary health centers over six months. We reported the information on a special order form for parenteral prescriptions and evaluated the selection and the dosing interval of each antibiotic. Of the 1084 treatments, cefonicid was the antibiotic most frequently prescribed (61.3 percent), followed by tobramycin (15.3 percent), cefotaxime sodium (6.7 percent), amikacin (3.8 percent), cefuroxime (3.8 percent), mezlocillin (3.7 percent), netilmicin sulfate (3.7 percent), ceftizoxime sodium (0.8 percent), cefoxitin (0.5 percent), and streptomycin sulfate (0.4 percent). Based on our survey criteria, 59 percent of the 710 orders that indicated diagnosis had a correct or possibly correct indication; the remaining percentage was considered unnecessary therapy or poor drug choice. Of the 1050 orders that indicated a dosing interval, 75.4 percent showed an appropriate dosing interval. We assume that most of the infections treated in our ambulatory care site could be resolved with or without common antibiotics. In this study we obtained objective data of the use of ten RAs in order to determine if their use in ambulatory patients was justified. We observed that a small number of prescriptions agreed with the recommended criteria stated in this survey for use of these antibiotics in outpatient infections.

Ambulatory Care↗
PubMed2000

Comparison of efficacy and safety of teicoplanin and vancomycin in children with antineoplastic therapy-associated febrile neutropenia and gram-positive bacteremia.

To compare their efficacy and safety, teicoplanin and vancomycin were randomly administered to 32 children for 52 gram-positive bacteremias during malignancy-associated neutropenia (<1000/microl). Patients mainly suffered from hematological malignancies. Twenty-five episodes were treated with teicoplanin (10 mg x kg(-1) x d(-1)) and 21 with vancomycin (40 mg x kg(-1) x d(-1)) plus ceftazidime and netilmicin. Six episodes were treated with teicoplanin because of previous "red man" reaction to vancomycin. Staphylococci (12% Staphylococcus aureus) were isolated from 50 episodes and viridans streptococci from 2. Defervescence on 3rd-4th day occurred in 29/31 (93.5%) teicoplanin-treated and 18/21 (85.7%) vancomycin-treated episodes. All 12 teicoplanin-treated and 13/13 vancomycin-treated episodes with repeat blood cultures on 3rd-4th day showed microbiological response. Two teicoplanin-treated and 3 vancomycin-treated patients required antifungals. Mild renal insufficiency appeared in 5 vancomycin-treated patients that was corrected without drug discontinuation. While both glycopeptides exhibit equal clinical and microbiological efficacy, teicoplanin is less likely to induce allergic reactions or nephrotoxicity in children.

Anti-Bacterial Agents↗
PubMed2000

Adequacy of a new chlorhexidine-bearing polyurethane central venous catheter for administration of 82 selected parenteral drugs.

OBJECTIVE: To screen 82 commonly used parenteral medications for compatibility with a new chlorhexidine-bearing central venous catheter, the ARROWg+ard Blue Plus. Evaluations were performed for completeness of drug delivery and impact, if any, of the drugs on the amount of chlorhexidine removed from the internal lumens. DESIGN: Drug solutions were prepared in dextrose 5% injection or NaCl 0.9% at common concentrations. Three 10-mL aliquots of each drug solution were delivered over 10 minutes, one aliquot through each lumen of the triple-lumen catheter. The initial drug concentrations of the admixtures and the effluent samples were analyzed by HPLC for chlorhexidine content and for the amount of drug delivered relative to its initial concentration. RESULTS: The delivery of the infusion solutions alone through sample catheters resulted in no more than trace amounts of chlorhexidine in the solution. Background amounts ranged from < 2.5 to 6.1 micrograms/mL in the first 10 mL of solution. Administration of none of the drugs tested resulted in a substantial increase in chlorhexidine delivery. Furthermore, delivery of most of the drugs was at least 95% and usually was in excess of 97% of the initial concentration. Concentrations of five drugs, amikacin sulfate, cefoperazone sodium, cefotaxime sodium, cefepime HCl, and netilmicin sulfate were somewhat lower than the initial concentration (range 91-95%), but were still considered acceptable. CONCLUSIONS: The ARROWg+ard Blue Plus central venous catheter can be recommended for use with all of the 82 parenteral drugs tested.

Catheterization↗
PubMed1998

In vitro activity of aminoglycosides on the respiratory burst response in human polymorphonuclear neutrophils.

In response to phagocytosis of microbes or chemical stimuli, neutrophils generate reactive oxygen species which represent the major bactericidal mechanism of these cells. We have investigated the influence of aminoglycosides (amikacin, gentamicin, netilmicin and tobramycin), antibiotics with a marked concentration-dependent killing effect, on the human neutrophil oxidative burst represented by the release of hydrogen peroxide. This study was performed using time-dependent cellular experiments and a cell-free system. In the cellular model, 2-h incubation with amikacin (ranging from 10 mg/l to 1 g/l), enhanced hydrogen peroxide release by stimulated human neutrophils. At higher concentrations (1 to 5 g/l), hydrogen peroxide production was decreased. No significant effects were observed with the other aminoglycosides at concentrations ranging from 10 mg/l to 2.5 g/l. The pro-oxidant activity of amikacin may be due to a cellular mechanism through oxidative metabolism of human neutrophils as demonstrated in the cell washing experiment, whereas the antioxidant activity observed for higher concentrations may be a result of a scavenging effect as demonstrated in the cell-free system. The enhanced of hydrogen peroxide production observed for therapeutic concentrations of amikacin could be a beneficial effect for neutrophil bactericidal functions.

Aminoglycosides↗
PubMed2005

Propolis: anti-Staphylococcus aureus activity and synergism with antimicrobial drugs.

Propolis is a natural resinous substance collected by bees from tree exudates and secretions. Its antimicrobial activity has been investigated and inhibitory action on Staphylococcus aureus growth was evaluated. The in vitro synergism between ethanolic extract of propolis (EEP) and antimicrobial drugs by two susceptibility tests (Kirby and Bauer and E-Test) on 25 S. aureus strains was evaluated. Petri dishes with sub-inhibitory concentrations of EEP were incubated with 13 drugs using Kirby and Bauer method and synergism between EEP and five drugs [choramphenicol (CLO), gentamicin (GEN), netilmicin (NET), tetracycline (TET), and vancomycin (VAN)] was observed. Nine drugs were assayed by the E-test method and five of them exhibited a synergism [CLO, GEN, NET, TET, and clindamycin (CLI)]. The results demonstrated the synergism between EEP and antimicrobial drugs, especially those agents that interfere on bacterial protein synthesis.

Anti-Bacterial Agents↗
PubMed1985

In vitro combination-effect of temocillin with ticarcillin and aminoglycosides on gram-negative and gram-positive bacteria.

The in vitro efficacy of temocillin in combination with ticarcillin and with gentamicin, tobramycin, amikacin and netilmicin against 80 Gram-negative and 20 Gram-positive bacterial strains was compared by use of the checkerboard agar dilution technique. No synergistic or additive effect was seen on the Gram-positive strains. Great variations occurred between the different bacterial species, and the temocillin-ticarcillin combination had only little effect against the Pseudomonas strains tested. On average, only 12% of all strains tested were inhibited synergistically by temocillin-gentamicin combinations, and only 7 to 10% by combinations of temocillin with the other aminoglycosides. However, 25% of Gram-negative strains were inhibited synergistically and 40% of Gram-negative strains were inhibited additively by the combination of temocillin-gentamicin.

Aminoglycosides↗
PubMed1985

A survey of temocillin sensitivity of strains resistant to newer beta-lactam antibiotics.

The susceptibility of a total of 2014 Gram-negative clinical isolates (except Pseudomonas aeruginosa) to a number of antibiotics, including temocillin, was investigated in 2 geographically distinct areas. Overall, more strains were sensitive to temocillin than to mezlocillin, piperacillin, amoxycillin plus clavulanic acid, cefotaxime, cephazolin, latamoxef (moxalactam), cefoxitin, or netilmicin. Susceptibility to temocillin of multiple-resistant strains was studied.

Bacterial Infections↗
PubMed1993

Use of the quinolones in the prophylaxis and treatment of granulocytopenic immunocompromised cancer patients.

The potential use of the quinolones in the prophylaxis and treatment of febrile episodes in granulocytopenic patients is reviewed. Of 7 controlled prophylactic studies performed with quinolones, 2 were double-blind and placebo-controlled. The occurrence of fever and mortality due to infection was not reduced with quinolone prophylaxis, although the occurrence of Gram-negative bacteraemia was significantly reduced. The delay to first fever was occasionally increased, and this was associated with a reduction in the number of days with antimicrobial agents. No effect was observed on disseminated fungal infections with quinolone prophylaxis. Breakthrough bacteraemia and subsequent infections were due to resistant organisms, mainly Gram-positive organisms (streptococci, staphylococci). Tolerability and compliance were excellent and were occasionally better than with the classic regimen [nonabsorbable antibiotics and cotrimoxazole (trimethoprim/sulfamethoxazole)]. Six controlled studies dealing with empiric treatment with the quinolones were reviewed. Overall, the results suggested that monotherapy with ciprofloxacin may be used in patients with a good prognosis (short and less severe neutropenia, solid tumours, compliant patients). Combinations with broad spectrum penicillins, netilmicin or teicoplanin seem to be as effective as the classic regimens (a broad spectrum penicillin or cephalosporin plus aminoglycosides), although the number of patients was limited (n = 334). The response rate of Gram-positive bacteraemia was lower with quinolone-containing regimens except for a combination that included teicoplanin.

Administration, Oral↗
PubMed1994

Parenteral aminoglycoside therapy. Selection, administration and monitoring.

Aminoglycosides are potent water-soluble antibiotics, with peak concentration-dependent bactericidal activity against many pathogenic aerobic Gram-negative bacilli and Staphylococcus aureus. For systemic therapy, they must be given parenterally (intravenously or intramuscularly). In the body they remain largely extracellular, but penetration into cerebrospinal fluid and other secretions is meagre. They display trough concentration-dependent reversible nephrotoxicity and The commonly irreversible ototoxicity, which may present after treatment ceases. Gentamicin is the usual all-purpose agent of choice, tobramycin is slightly more effective against Pseudomonas aeruginosa infections, amikacin is the least susceptible to degradation by bacterial enzymes and netilmicin is probably the least toxic. Clinical and drug concentration monitoring have a role in therapy. Aminoglycosides exhibit enduring antibacterial activity (especially against Gram-negative bacilli) many hours after tissue concentrations become negligible. Appreciation of this postantibiotic effect is leading to replacement of conventional multiple daily doses by large single daily doses. The latter regimens confer at least equivalent efficacy and less risk of toxicity (particularly renal). However, single daily dosage may be unsuitable for immunocompromised patients and in those with infective endocarditis, where there is insufficient experience. Cotreatment with beta-lactams is commonly used in order to exploit the synergism between these agents, particularly in enterococcal endocarditis and severe Gram-negative sepsis. Liposomal aminoglycosides are promising parenteral formulations. After being taken up by phagocytes they reach the liver, spleen and sites of inflammation; subsequently they are gradually released. To substantiate the applicability of these hitherto experimental formulations, findings from clinical studies are keenly awaited.

Aminoglycosides↗
PubMed1997

Recognition and optimum treatment of brucellosis.

Brucellosis (infection with Brucella spp.) is a common zoonosis in many parts of the world. Human brucellosis is a multisystem disease that may present with a broad spectrum of clinical manifestations. Treatment of brucellosis must effectively control acute illness and prevent complications and relapse. The choice of regimen and duration of antimicrobial therapy should be based on the presence of focal disease and underlying conditions which contraindicate certain specific antibiotics. The regimen of first choice is combination therapy with doxycycline for 45 days and streptomycin for 14 days. Gentamicin or netilmicin for the first 7 days may be substituted for streptomycin. Second-choice regimens consist of combinations of doxycycline and rifampicin (rifampin) for 45 days, or monotherapy with doxycycline for 45 days. Surgery should be considered for patients with endocarditis, cerebral or epidural abscess, spleen abscess or other abscesses which are antibiotic-resistant. Tetracyclines are generally contraindicated for pregnant patients and children < 8 years old. Rifampicin 900 mg once daily for 6 weeks is considered the drug of choice for treating brucellosis in pregnant women. In children < 8 years old the preferred regimen is rifampicin with cotrimoxazole (trimethoprim-sulfamethoxazole) for 45 days. An alternative regimen consists of a combination of rifampicin for 45 days with gentamicin 5 to 6 mg/kg/day for the first 5 days.

Adult↗
PubMed1984

Sensitivity of 523 blood culture isolates to 33 antibiotics.

523 blood culture isolates collected during 18 months (July 1980-December 1981) were analysed by the agar dilution method for sensitivity to 33 antibiotics. Breakpoints corresponding to the SIR system were used but for N-formimidoyl-thienamycin (N-f-thienamycin), azthreonam and fosfomycin serial dilutions were made. Aminoglycosides (netilmicin, gentamicin, amikacin and tobramycin) inhibited from 90 to 86% of the strains. This was comparable to the percentage inhibited by some cephalosporins (cefotaxime, cefoperazone, ceftazidime, ceftriaxone, cefuroxime, cephamandole and moxalactam) ranging from 95 to 89%. A very high number of strains (99%) were inhibited by N-f-thienamycin. By combination of certain antibiotics more than 99% of the strains could be inhibited.

Acinetobacter↗
PubMed1992

A 56-month prospective surveillance study on the epidemiology of aminoglycoside resistance in a Belgian general hospital.

In this survey, we studied the effect of extensive amikacin usage on the epidemiology of aminoglycoside resistance in a general hospital. The baseline resistance in the 12 months before amikacin was 5.8% for amikacin, 15.2% for gentamicin, 16.4% for tobramycin and 14.0% for netilmicin. During the following 44 months, amikacin was the aminoglycoside of first choice. In the first 2 years of this phase, resistance to amikacin did not change significantly. Later, amikacin resistance rose significantly, mainly due to the introduction of amikacin-resistant Enterobacter aerogenes strains. In general there was a significant decrease in resistance to gentamicin and tobramycin. Resistance mechanisms were examined in 380 strains. AAC(3)V, and AAC(6')I alone or coupled with ANT(2") or AAC(3) were the most prevalent enzymes. In the amikacin phase, we noticed a significant increase of strains harbouring the AAC(6')I enzyme, while strains with the AAC(3)V were less frequently isolated. Strains with permeability resistance did not become more prevalent during the period of extensive amikacin use.

Amikacin↗
PubMedDate not supplied

Febrile episodes in children with cancer in the United Arab Emirates.

The febrile episodes encountered in our pediatric oncology unit over a 2-year period were reviewed. A total of 138 febrile episodes were recorded in 59 patients (29 with leukemia and 30 with a solid tumor). There was no difference in the number of episodes between leukemia and solid tumor patients, nor between neutropenic and non-neutropenic patients. The degree of neutropenia was more severe in leukemia patients. A total of 18.8% of the episodes were accompanied by positive blood cultures. Gram-positive bacteria were more frequent than gram-negative bacteria, and there were four anaerobic isolates. Seventeen episodes were accompanied by clinical signs of central venous line (CVL) infection. A total of 70.2% of the episodes resolved with a first-line antibiotic combination of flucloxacillin, piperacillin, and netilmicin, 27.5% required modification of the antibiotic combination, and three patients (5%) died due to gram-negative septicemia. These findings indicate that the pattern of infectious complications in the United Arab Emirates is now similar to that observed in Europe and the United States.

Bacteremia↗
PubMed1983

Treatment of chronic pseudomonas aeruginosa infection in cystic fibrosis patients with ceftazidime and tobramycin.

50% inhibitory concentration (IC50) and minimum inhibitory concentration (MIC) of ceftazidime, cefsulodin, cefotaxime, moxalactam, azlocillin, carbenicillin, netilmicin and tobramycin against 90 strains of Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients were determined by means of the agar plate dilution method. Ceftazidime was most active of the antibiotics in vitro; the geometric mean of IC50 was 0.2 and of MIC 0.4 micrograms/ml. 11 CF patients suffering from P. aeruginosa infection were treated with 14 day courses of ceftazidime (100 mg/kg/24 h) and tobramycin (10 mg/kg/24 h). P. aeruginosa was only temporarily eradicated in one of the patients, but a significant improvement of respiratory function and a significant fall in white blood cell count was recorded in the patients during chemotherapy. There was no development of resistant strains against ceftazidime during treatment and no side-effects were observed. Ceftazidime is a promising new antimicrobial agent with high in vitro activity which deserves further in vivo evaluation in CF patients.

Adolescent↗