Piperacillin + Tazobactam Kabi 4 g + 0.5 g No. 10 bottles
Content
Indications Dosage regimen Side effects Contraindications for use Use during pregnancy and breastfeeding Use for impaired renal function Use in children Special instructions Drug interactions
Indications
Bacterial infections caused by sensitive microflora in adults and children over 12 years of age: infections of the lower respiratory tract (pneumonia, lung abscess, pleural empyema); abdominal infections (peritonitis, pelvioperitonitis, cholangitis, gallbladder empyema, appendicitis (including complicated by an abscess or perforation)). urinary tract infections, incl. complicated (pyelonephritis, cystitis, prostatitis, epididymitis, gonorrhea, endometritis, vulvovaginitis, postpartum endometritis and adnexitis); infections of bones and joints, including osteomyelitis; infections of the skin and soft tissues (phlegmon, furunculosis, abscess, pyoderma, lymphadenitis, lymphangitis, infected trophic ulcers, infected wounds and burns); intra-abdominal infections (including in children over 2 years old); bacterial infection in patients with neutropenia (including children under 12 years of age); sepsis; meningitis; prevention of postoperative infection.
Dosage regimen
The method of administration and dosage regimen of a particular drug depend on its release form and other factors. The optimal dosage regimen is determined by the doctor. The compliance of the dosage form of a particular drug with the indications for use and dosage regimen should be strictly observed.
Intravenously.
Side effect
- Allergic reactions: urticaria, pruritus, rash, bullous dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactic/anaphylactoid reactions (including anaphylactic shock).
- From the digestive system: diarrhea, nausea, vomiting, constipation, dyspepsia, jaundice, stomatitis, abdominal pain, pseudomembranous colitis, hepatitis.
- From the hematopoietic organs: leukopenia, neutropenia, thrombocytopenia, anemia, bleeding (including purpura, nosebleeds, increased time, bleeding), hemolytic anemia, agranulocytosis, false-positive direct Coombs test, pancytopenia, increased partial thromboplastin time, increased prothrombin time, thrombocytosis.
- From the urinary system: interstitial nephritis, renal failure.
- From the nervous system: headache, insomnia, convulsions.
- From the cardiovascular system: decreased blood pressure, “flushes” of blood to the facial skin.
- Laboratory indicators: hypoalbuminemia, hypoglycemia, hypoproteinemia, hypokalemia, eosinophilia, increased activity of “liver” transaminases (alanine aminotransferase, aspartate aminotransferase), hyperbilirubinemia, increased activity of alkaline phosphatase, gamma-glutamyltransferase, increased concentration of creatinine and urea in the blood serum.
- Local reactions: phlebitis, thrombophlebitis, hyperemia and compaction at the injection site.
- Other: fungal superinfections, fever, arthralgia.
Contraindications for use
Hypersensitivity (including to penicillins, cephalosporins, other beta-lactam antibiotic inhibitors); children's age (up to 2 years).
With caution
Severe bleeding (including history), cystic fibrosis (increased risk of developing hyperthermia and skin rash), pseudomembranous colitis, children over 2 years of age, chronic renal failure (creatinine clearance less than 20 ml/min), patients on hemodialysis , with the combined use of high doses of anticoagulants, with hypokalemia, pregnancy, lactation.
Use during pregnancy and breastfeeding
Use with caution during pregnancy and lactation (breastfeeding).
Use for renal impairment
With caution: chronic renal failure. For chronic renal failure, daily doses of piperacillin/tazobactam are adjusted depending on the CC.
Use in children
Contraindication: children under 2 years of age.
With caution: children over 2 years of age.
special instructions
During treatment, especially long-term treatment, leukopenia and neutropenia may develop, so it is necessary to periodically monitor peripheral blood levels.
In some cases (most often in patients with renal failure), increased bleeding and concomitant changes in laboratory parameters of the blood coagulation system (blood clotting time, platelet aggregation and prothrombin time) are likely to occur. If bleeding occurs, the drug should be discontinued and appropriate therapy should be prescribed.
Antibiotic-induced pseudomembranous colitis can present with severe, persistent diarrhea that is life-threatening. Pseudomembranous colitis can develop both during the period of antibacterial therapy and after its completion. In such cases, the drug should be stopped immediately and appropriate therapy should be prescribed (for example, oral metronidazole, vancomycin). Drugs that inhibit intestinal motility are contraindicated.
It is necessary to keep in mind the possibility of the emergence of resistant microorganisms that can cause superinfection, especially with a long course of treatment. This drug contains 2.79 mEq (64 mg) of sodium per gram of piperacillin, which may result in an overall increase in sodium intake. In patients with hypokalemia or taking drugs that promote potassium excretion, hypokalemia may develop during treatment (it is necessary to regularly check the content of electrolytes in the blood serum).
In patients with chronic renal failure on hemodialysis, the dose of the drug and frequency of administration must be adjusted depending on the CC.
During use, a false positive test result for glucose in urine is possible when using a method based on the reduction of copper ions. Therefore, it is recommended to carry out a test based on the enzymatic oxidation of glucose (glucose oxidase method).
Impact on the ability to drive vehicles and machinery
Considering the possibility of developing side effects from the nervous system during treatment with the drug, caution should be exercised when working with machinery and driving vehicles.
Drug interactions
Co-administration of the drug with probenecid increases the half-life and reduces the renal clearance of both piperacillin and tazobactam, however, Cmax in the plasma of both drugs remains unchanged.
The simultaneous use of the drug and vecuronium bromide can lead to a more prolonged neuromuscular blockade caused by the latter (a similar effect can be observed when piperacillin is combined with other non-depolarizing muscle relaxants).
With the simultaneous use of high doses of heparin, indirect anticoagulants or other drugs that affect the blood coagulation system, including platelet function, it is necessary to monitor the condition of the blood coagulation system more often.
Piperacillin may delay the elimination of methotrexate (to avoid toxic effects, it is necessary to monitor the concentration of methotrexate in the blood serum).
Pharmaceutical compatibility with other drugs
Do not mix in the same syringe or dropper with other medications, incl. with aminoglycosides. When used together with other antibiotics, the drugs should be administered separately; It is most preferable to separate the administration of piperacillin + tazobactam and aminoglycosides in time.
Should not be used in conjunction with solutions containing sodium bicarbonate or added to blood products or albumin hydrolysates.
Modern achievements and problems of empirical treatment of infection in patients with neutropenia
Myelotoxicity is one of the main complications of cytostatic therapy for tumor diseases, leading to a decrease in the content of blood cells (leukocytes, erythrocytes and platelets). Particularly dangerous is the development of neutropenia, the fundamental role of which in the occurrence of severe infection was identified more than 30 years ago [1, 2]. The rapid progression of infection, high mortality in the absence of effective treatment and differences in the effectiveness of antibiotics in patients with neutropenia made it possible to allocate patients with this type of infectious complications into a separate group.The last 30 years have been marked by significant advances in the treatment of patients with neutropenic infection. The use of modern antibiotic regimens has made it possible to reduce mortality from this dangerous complication by more than 10 times. At the same time, problems remain related to the development of microbial resistance, as well as the spread of new pathogens that are more resistant to modern anti-infective drugs.
In 1960–1970 gram-negative bacterial pathogens
(Escherichia coli, Klebsiella and Pseudomonas aeruginosa) were prevalent in patients with neutropenia.
In the 80s, gram-positive pathogens
(streptococci and staphylococci, among which resistant strains are often found), took the leading role among the causative agents of infection in this group of patients. Many authors explain this by the frequent use of intravenous catheters, the prophylactic use of fluoroquinolones and the widespread use of antitumor drugs that cause mucositis (anthracyclines, cytosar). While in the first controlled studies, organized in the early 70s by the Neutropenic Infection Group of the European Society for Research and Treatment of Cancer (EORTC), the proportion of Gram-negative infections in single-pathogen bacteremia was 70%, then in the 90s it decreased to 30% [ 3]. At the same time, the representation of gram-negative pathogens, especially Pseudomonas aeruginosa, remains significant.
of fungal pathogens in the etiology of infectious complications in patients with neutropenia has increased significantly.
. According to an international study, systemic fungal infection occurred in 25% of deceased patients with leukemia, 12% with lymphomas, and 5% with solid tumors [4]. Quite often, patients with neutropenia also experience herpetic infections.
Therapeutic approaches to patients with infection and neutropenia have undergone significant changes over 30 years, due to the early use of empirical antimicrobial therapy with broad-spectrum drugs in practice. Fever in neutropenic patients is often the only sign of early infection and is sufficient reason to initiate systemic antibiotic therapy. “febrile neutropenia” is widely used to characterize patients with such complications.
.
According to the criteria of the Infectious Diseases Society of America, this term refers to at least a 2-fold increase in body temperature per day of more than 380 C or a single increase in temperature of more than 38.30 C in patients with a neutrophil count of less than 1000 per μl
.
The occurrence of this symptom complex serves as the basis for carrying out diagnostic procedures (thorough examination of the patient, x-ray examination of the chest and, if indicated, ultrasound of the abdominal cavity, bacteriological examination of the blood and all potential foci of infection) and the immediate initiation of empirical antibiotic therapy. Such empirical therapy should be directed against gram-positive and gram-negative microorganisms (including Pseudomonas aeruginosa), have rapid bactericidal activity and low toxicity. The choice of therapy should also take into account the sensitivity of common hospital pathogens in a given department and cost-effectiveness.
Combined treatment
Historically, combinations of antibiotics that are active against a variety of Gram-negative pathogens and are synergistic in vitro have often been used to treat infection in neutropenic patients. The EORTC Neutropenic Infection Group clinical trial showed a statistically significant benefit of combining a b-lactam and an aminoglycoside in the treatment of gram-negative bacteremia
[5]. The aminoglycoside, along with enhancing the action of b-lactam, helps control infection in case of resistance to the latter. However, the use of aminoglycoside-containing combinations increases the risk of nephrotoxicity and in some cases requires additional equipment to monitor the concentration of the antibiotic in the blood. At the same time, the clinical advantage of such combinations is shown only for gram-negative bacteremia, which occurs more often in patients with prolonged granulocytopenia. The number of such patients is small and amounted to about 3.5% in the last three EORTC studies.
Use of combinations including two b-lactams
(eg, piperacillin and moxolactam), is also a highly effective treatment for febrile neutropenia and has less nephrotoxicity compared with aminoglycoside and b-lactam combinations. At the same time, the cost of such treatment is higher and blood clotting disorders are more often observed due to a decrease in the synthesis of prothrombin complex proteins.
Monotherapy
The appearance in clinical practice of active antibiotics with a wide spectrum of action, such as ceftazidime
,
imipenem
,
meropenem
,
cefepime
,
piperacillin/tazobactam
, has opened up new therapeutic options.
The use of a single antibiotic in patients with neutropenic infection could reduce toxicity and reduce treatment costs. The first comparative clinical study with ceftazidime
showed that its use is no less effective than the use of a combination of carbenicillin, cephalothin and gentamicin [6].
The effectiveness of the combination of imipenem and amikacin was comparable to the effectiveness of imipenem
(76 and 72%, respectively) [7].
Similar data were obtained when comparing the effectiveness of meropenem
with a combination of ceftazidime and amikacin in patients with neutropenic infection [8].
Several controlled studies have been conducted with IV generation cephalosporins. The effectiveness of cefepime
was no less than that of combinations of ceftazidime with amikacin and piperacillin with gentamicin [9].
, piperacillin/tazobactam
monotherapy was no less effective than combination therapy with ceftazidime and amikacin [10].
The comparable effectiveness of monotherapy and a combination of antibiotics in the treatment of febrile neutropenia can be explained by the increased etiological significance of gram-positive flora, which in recent years has made up the bulk of all isolated pathogens.
These were mainly staphylococci.
Staphylococcal infections have a less severe and life-threatening course. In contrast, infection caused by streptococci can occur with lightning speed and lead to death in the absence of effective treatment
.
In hospitals with a high risk of streptococcal infection, it is advisable to prescribe drugs that are most active against this pathogen. In a controlled comparative study, the combination of piperacillin/tazobactam with amikacin
was more effective in the treatment of streptococcal infection than the combination of ceftazidime with amikacin [11].
Many of the episodes of febrile neutropenia analyzed in the studies occurred in patients with solid tumors
receiving less aggressive cytostatic therapy than patients with hemoblastosis.
In a significant proportion of them, no microbiological or clinical signs of infection can be detected (with the exception of fever during neutropenia), and empirical antibiotic therapy in this group is usually highly effective. There is no doubt that in these patients, monotherapy with a broad-spectrum antibiotic
(cefepime, ceftazidime, imipenem or meropenem) at the first stage is quite adequate and its modification is necessary only when clinical or microbiological data are obtained.
Such a scheme is not always applicable to the subgroup of patients with profound long-term neutropenia
.
In some of these patients, monotherapy may be effective, however, due to the high risk of infection caused by gram-negative bacteria, it is advisable to prescribe combination therapy already at the first stage of treatment
.
Choice of first-line drugs
Despite the fact that at least 5 drugs (ceftazidime, cefepime, piperacillin/tazobactam, imipenem and meropenem) showed similar positive results when used in the first line treatment of febrile neutropenia.
, there are some differences in their effectiveness. These differences may determine the choice of antibiotic in a particular situation, depending on the expected duration of neutropenia, the patient's condition and the sensitivity spectrum of the flora prevailing in a given department.
Ceftazidime
historically was one of the first broad-spectrum b-lactams, whose effectiveness in monotherapy in the treatment of febrile neutropenia was equivalent to a combination of antibiotics.
At the same time, its activity against gram-positive pathogens, which currently constitute up to 70% of infectious agents in neutropenia, is the lowest of the first-line drugs. When studying the sensitivity of pathogens of hospital infections, carried out in several centers in Russia (Table 1), insufficient activity of ceftazidime against gram-positive microbes
,
especially staphylococci
.
When choosing a treatment regimen for a neutropenic infection, it is also necessary to take into account the fact that the sensitivity of gram-positive pathogens that cause infection in patients with neutropenia has decreased over the past 20 years. Controlled studies from the EORTC Neutropenic Infection Group show a progressive decrease in the success rate of combinations of some beta-lactams and aminoglycosides in the treatment of infections caused by these pathogens (Table 2).
Monotherapy with ceftazidime in a number of studies was accompanied by a high incidence of gram-positive superinfection compared to other antibiotics [13]. Thus, if the risk of gram-positive infection is high
cefepime, piperacillin/tazobactam or carbapenems may be preferred
as a first-line drug .
In the case of a high frequency of methicillin-resistant strains of staphylococcus, the only effective drug may be a glycopeptide (vancomycin or teicoplanin).
With the widespread use of ceftazidime, there is a risk of selection of certain strains of Enterobacter spp., which constantly produce a large number of chromosomal class C b-lactamases, capable of destroying most b-lactam antibiotics (including third-generation cephalosporins and b-lactamase inhibitors). In some departments, the increase in the number of b-lactamase-hyperproducing strains of Enterobacter spp. is becoming epidemic [14], and it is important to know that in this case, IV generation cephalosporins (cefepime) and carbapenems (imipenem and meropenem) remain highly active.
Recently, strains of Klebsiella spp that produce extended-spectrum b-lactamases capable of successfully destroying all penicillins, cephalosporins and monobactams (aztreonam) are often considered as a problematic microorganism. There are difficulties in diagnosing resistant strains of this pathogen, which are often incorrectly considered to be sensitive to third-generation cephalosporins. In most cases, resistant strains of Klebsiella spp. retain sensitivity to carbapenems and, although to a lesser extent, to IV generation cephalosporins [15].
Activity spectrum of carbapenems
is the broadest of the group of drugs active in the treatment of infection in patients with neutropenia.
They are active against most gram-positive (with the exception of methicillin-resistant staphylococci and some enterococci) and gram-negative pathogens, as well as anaerobes. The latter effect of carbapenems may promote fungal or clostridial superinfection by damaging intestinal colonization resistance [16]. There are no fundamental differences between meropenem and imipenem, with the exception of tolerability
. If the tolerability of meropenem corresponds to the good tolerability of cephalosporins, then the use of imipenem is quite often complicated by disorders of the gastrointestinal tract and the development of seizures. The incidence of seizures when prescribed imipenem, according to large registries, is about 1% [17], and in the case of high doses of the drug (4 g per day) can reach 2.5–10% [7]. Although most successful controlled studies with imipenem in the treatment of febrile neutropenia were conducted at a dose of 4 g per day, there is evidence that a lower dose of the drug or its reduction after several days of treatment to 2 g per day is also highly effective [18]. The widespread use of imipenem as a first-line drug can quickly lead within a department or hospital to the selection of Pseudomonas aeruginosa strains resistant to this drug and to an increase in the infections caused by them [19].
Modification of the initial treatment regimen
Even with the most effective combination or monotherapy regimens, 30 to 70% of patients do not respond to the initial antibiotic regimen
[20].
Most often, the ineffectiveness of first-line therapy is due to the presence of methicillin-resistant strains of staphylococci, which are highly resistant to most b-lactams and aminoglycosides. Due to the increasing role of gram-positive pathogens, including those resistant to first-line drugs, glycopeptides - vancomycin and teicoplanin -
. These antibiotics are highly active against multidrug-resistant gram-positive flora and are added to first-line drugs if signs of infection persist. They are usually not included in initial therapy for two reasons: first, the controlled EORTC trial showed that delaying the administration of vancomycin until the effectiveness of the first treatment regimen was assessed did not worsen the overall treatment results, but reduced the need for its administration by 2 times [20], and , secondly, glycopeptides are nephrotoxic and increase the risk of fungal superinfection. An important consideration leading to more economical use of glycopeptides is the possibility of resistance development. Over the past 10 years, there has been a significant increase in the minimum inhibitory concentration (MIC) of vancomycin for many representatives of gram-positive microorganisms isolated from patients with febrile neutropenia. If in the early 80s the MIC of vancomycin for the vast majority of these microbes, including enterococci, was less than 1 μg/ml, then in the 90s it increased 4–8 times (Table 3). The minimum bactericidal concentration (MBC) also increased.
In some centers that widely use glycopeptide antibiotics, the emergence of vancomycin-resistant enterococci creates a serious problem in the selection of an extremely dangerous pathogen. All these considerations allow, in most cases, to delay the initiation of glycopeptides until culture results are available or the ineffectiveness of the first regimen is identified.
. However, in hospitals with a predominance of methicillin-resistant staphylococci, as well as with clinical prerequisites for a gram-positive infection (infection of the catheter or external skin) and the patient’s serious condition, glycopeptides can be used in combination in the first line of treatment.
Treatment of fungal infection
The second most common reason for failure of the initial treatment regimen for febrile neutropenia is fungal infection.
Among its main pathogens,
Candida and Aspergillus predominate.
, cryptococci, trichosporon and fusarium
have also often been isolated from patients with immune disorders . Infection caused by the latter pathogen has clinical manifestations similar to aspergillosis with a higher risk of systemic spread.
One of the main problems in treating fungal infections is the difficulty of diagnosing them. Retrospective analysis suggests that all diagnostic procedures can detect candidemia only in 35–45% of cases
in patients with disseminated candidiasis confirmed by autopsy.
In this regard, it is customary to prescribe antifungal agents to patients who have had a fever for 3–4 days during antibiotic therapy. For many years, due to its broad spectrum of activity, including the main pathogens of fungal infections, and its fungicidal effect, amphotericin B
. According to controlled studies, early empirical administration of this drug eliminates signs of infection in approximately 10% of patients with fever that persists during antibiotic therapy [21]. In one controlled trial, early empirical administration of amphotericin B resulted in a reduction in mortality from fungal complications [22].
The toxicity of amphotericin B is significant, and in recent years, the use of triazole antifungals (fluconazole and itraconazole)
, which have better tolerability. There is evidence that in chronic disseminated candidiasis, the use of fluconazole is more effective than amphotericin B [23, 24]. In two controlled studies, empirical administration of fluconazole in patients with febrile neutropenia was no less effective than administration of amphotericin B, with less toxicity [25]. In cases of fungal infection where fluconazole was ineffective, switching to amphotericin B was successful. There is currently sufficient evidence to recommend the use of fluconazole for empirical therapy in patients with febrile neutropenia, especially those with impaired renal function.
The disadvantage of the empirical use of fluconazole is the lack of effect against Aspergillus. Itraconazole
has a wider spectrum of activity, including aspergillus. At the same time, this drug does not have a parenteral form, and its pharmacokinetic parameters when taken orally are unstable. The second problem with the use of azoles is the resistance of some species of candida (C.krusei, C.glabrata) to them. The incidence of these pathogens and the infections they cause increases significantly in patients treated prophylactically with fluconazole and itraconazole.
Some new triazole derivatives ( voriconazole
) have a wide spectrum of activity, including Candida and Aspergillus. Voriconazole has a fungicidal effect against Aspergillus in vitro. This drug was effective in patients with neutropenia and fungal infection in phase II clinical trials, and its activity is being studied in phase III trials.
Currently, despite some toxicity, amphotericin B
remains the most used drug for empirical treatment of fungal infections.
The ability of this drug to reduce the risk of systemic mycoses and death from fungal infections in empirical therapy in patients with neutropenia, proven in randomized studies, allows us to recommend amphotericin B as the most effective. At the same time, many authors describe cases of “breakthrough” infection caused by fungi of the genus Aspergillus, Fusarium or Trichosporon beigelii during therapy with amphotericin B [26]. This may be partly due to the use of an insufficient dose of amphotericin B, as its increase from 0.5–0.7 mg/kg/day to 1–1.5 mg/kg/day in patients with invasive aspergillosis that developed during empirical use of this drug led to clinical cure [27]. The use of higher doses of amphotericin increases the severity of side effects. The tolerability of amphotericin B can be improved by creating liposomal, less toxic and more effective forms of the drug. This is especially important in the treatment of aspergillus infections, when it is necessary to administer high doses. A study on the use of a liposomal form of amphotericin B
(Ambysome) showed that its use is no less effective and significantly less toxic than the use of amphotericin B [28]. Patients who developed nephrotoxicity, including renal failure, during treatment with amphotericin B were able to successfully complete treatment when switched to Ambisome.
Hematopoietic growth factors
When treating resistant (especially fungal) infections in neutropenic patients, restoring granulocyte counts is a critical factor for success. From this point of view, the use of granulocyte and granulocyte-macrophage colony-stimulating factors
(G-CSF and GM-CSF) is promising for stimulating granulocytopoiesis and reducing the duration of critical neutropenia.
Studies on the prophylactic administration of G-CSF and GM-CSF have shown their high effectiveness in reducing the duration of neutropenia and the number of infectious episodes in patients with solid tumors and lymphomas receiving hemosuppressive chemotherapy. At the same time, mortality from infection in most cases has not changed. Most likely, this was determined by the overall low mortality with standard chemotherapy. In contrast, in elderly patients with acute leukemia, early post-chemotherapy mortality reaches 30–50%, which is largely due to severe neutropenic infection. In a controlled study, prophylactic administration of GM-CSF in elderly patients (55–70 years old) with acute non-lymphoblastic leukemia reduced the incidence of severe infection and early mortality after chemotherapy by 2 times
. This increased overall survival compared to the control group [24]. A similar study conducted in patients with standard-risk non-lymphoblastic leukemia who received prophylactic G-CSF found a reduction in the duration of profound neutropenia and hospitalization, and also reduced the need for antifungal therapy. This made it possible to significantly reduce treatment costs.
There is positive experience with the use of myelocytokines in conjunction with antibiotics in patients with already developed infection and neutropenia.
Controlled studies have shown that with a deep drop in neutrophils (less than 100 cells), the administration of G-CSF almost halves the duration of neutropenia, hospitalization and antibiotic therapy. The need for antifungal therapy is also reduced by 2 times [29]. The latter fact is quite important if we take into account the toxicity of some antifungal drugs. The use of GM-CSF in a similar situation together with antibiotics showed a significantly better effect of antibiotic therapy in the cytokine group in the treatment of tissue verified infection (100% effectiveness versus 59% in the placebo group). References
1. Bodey JP, Buckley M, Sathe Y et al. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann.Intern.Med. 1966, 64: 328–3401.
2. Bogomolova N.S., Karabak V.I., Akhmedova S.V. et al. Results of a multicenter study of the comparative activity of cefepime and other antibiotics against pathogens of severe hospital infections (Micromax). Antibiotics and chemotherapy. 1999; 44 (11): 4–14.
3. Rolston KVI, Raad I., Wimbey E. et al. The changing spectrum of bacterial infections in febrile neutropenic patients. In: Febrile neutropenia. JAKlasterski (ed.) Springer 1997; 53–6.
4. Bodey JP, Bueltmann B, Duguid W et al. An international autopsy survey. Eur. J. Microbiol. Infect. Dis. 1992; 15:99–109.
5. EORTC International Antimicrobial Therapy Co-operative Group. Ceftazidim combined with short or long course of amikacin for empirical therapy of gram-negative bacteremia in cancer patients with neutropenia. New Engl. J. Med. 1987; 317:1692–8.
6. Pizzo PA, Hathorn JW, Himenz J. et al. A randomized trial comparing ceftazidim alone with combination antibiotic therapy in cancer patients with fever and neutropenia. N.Engl.J.Med. 1986; 315:552–8.
7. Rolston VKI, Birkey P, Bodey GP et al. A comparison of imipenem to ceftazidim with or without amikacin as empiric therapy in febrile neutropenia patients. Arch Intern Med. 1992; 152:283–91.
8. EORTC International Antimicrobial Therapy Cooperative Group. Monotherapy with meropenem versus combination therapy with ceftazidim plus amicacin as empiric therapy for fever in granulocytopenic patients with cancer. Antimicrob. Agents. Chemother. 1995; 40: 1108–15.
9. Ramphal R., Gulcap R., Rotstain C. et al. Clinical experience with single agent and combination regimens in the management of infection in the febrile neutropenic patient. Am. J. Med. 1996; 100 (Suppl. 6a): 83.
10. Hess K. et al. Support. Care Cancer 1998; 6:402.
11. Cometa A., Zinner S., de Bock T. et al. Piperacillin-Tazobactam plus Amikacin versus Ceftazidim plus Amikacin as empiric therapy for fever in granulocytopenic patients with cancer. Antimicrob. Ag. Chemother. 1995; 39: 445–52.
12. Cometta A., Viscoli C., Castagnola E., et al. Empirical treatment of fever in neutropenic children: the role of carbapenems. Pediatr. Inf.Dis.J. 1996; 15: 744–78.
13. Kramer BS, Ramphal R., Rand K. Randomized comparison between two ceftazidime regimens and containing cefalothin-gentamicine-carbenicillin in febrile granulocitopenic cancer patients Antimicrob. Ag. Chemother. 1986; 30:64–8.
14. Mebis J., Goosens H., Bruineel P. et al. Deccreasing antibiotic resistance of Enterobacterioceae by introducing a new antibiotic combination therapy foe neutropenic fever patients, 1998; 12:1627–9.
15. Sanders CC Cefepime: The next generation. The reason and rationale behind its development. Drugs Today, 1995; 31:221–5.
16. De Paw BE, Boogaerts MA, Goldstone AH Equuivalent efficacies of meropenem and ceftazidime as empirical monotherapy of febrile neutropenic patients. J.Antimicrob.Chemother. 1995; 36: 185–200.
17. Calandra T., Lydick E., Carrigan J. Factors predisposing to seizures in seriosly ill infected patients receiving antibiotics: experience with imipenem-cilastatin. Am J Med 1988; 84:911–18.
18. Winston DJ, Ho WG, Bruckner DA, Champlin RE Betalactam antibiotic therapy in febrile granulocitopenic patients. Ann. Intern. Med. 1991; 115:849–59.
19. Rahal JJ, Urban C, Horn D et al. Limiting the use of cephalosporins to combat general cephalosporin resistance in nosocomial bacteria of the genus Klebsiella. JAMA-Russia, vol. 2 (8) 32–9.
20. EORTC International Antimicrobial Therapy Cooperative Group and NCI of Canada Clinical Trials Group (1991) Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. J.Infect.Dis. 1991; 163:951–58.
21. Marcus RE, Goldman JM Management of infection in the neutropenic patients. Br. Med. J. 1986; 293:406–8.
22. EORTC International Antimicrobial Therapy Cooperative Group (1989) Empiric antifungal therapy in febrile granulocytopenic patients. Am. J. Med. 1989; 86:668–72.
23. Anaissie E., Bodey GP, Kantarjian H. et al. Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy. Am.J.Med. 1991; 91: 142-50.
24. Rowe JM, Andersen JW, Mazza JJ et al. A randomized placebo-controlled Phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (>55 to 70 years of age) with acute myelogenous leukemia: A study of the Eastern Cooperative Oncology Group (E1490). Blood, 1995; 86:457–62.
25. Viscoli C, Castagnola E, Van Lint MT et al. Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicenter, prospective and randomized trial. Eur J Cancer 1996; 32:814–20.
26. Walsh TJ, Melcher GP, Rinaldi MG et al. Trichosporon beigelii an emerging pathogen resistant to amphotericin BJClin.Microbiol.1990; 28: 1616–22.
27. Burch PA, Karp JE, Merz WG et al. Favorite outcome of invasive aspergillosis in patients with acute leukemia. J.Clin.Oncol. 1987; 5: 1985–93.
28. Prentice HG, Hann IM, Herbrecht R. et al. A randomized comparison of liposomal versus conventional Amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Brit. J. Haematol. 1997; 98:711–8.
29. Macher D., Green M., Bishop J. et al. Randomized, placebo controlled trial of filgrastim in patients with febrile neutropenia following chemotherapy. Proc ASCO 1993;12: 434 (abstr).
Piperacillin + tazobactam
—
Tazocin
(trade name)
(Wyeth-Lederle)
Appendices to the article
| Fever in neutropenic patients is often the only early sign of infection and an indication for systemic antibiotic therapy |
| Most often, the failure of first-line therapy is due to the presence of methicillin-resistant strains of staphylococci |
| It is customary to prescribe antifungal agents to patients who have had a fever for 3–4 days during antibiotic therapy. |
