Febrile neutropenia

Febrile neutropenia, or "neutropenic fever" is a condition where the level of neutrophils (less than five hundred) in the blood plasma of a person falls quite suddenly and immediately in a very severe form.

Progression of this state is fraught with a life threat.

[1],

Causes of the febrile neutropenia

The severe condition of the patient and the likelihood of manifestation of even greater health problems, expressed by complications of bacterial and infectious genesis, directly depend on the level of neutrophils in the serum. Low values of the number of these blood cells from the leukocyte group and determine the severity of neutropenia. The causes of febrile neutropenia can be:

• The consequences of cytostatic chemotherapy, which was conducted in connection with the diagnosis of leukemia.
• A little less often after a similar procedure, but in connection with the diagnosis of cancerous lesions of other areas of the lesion.
• It is very rare, but cases have been documented after radiotherapy.
• Congenital pathologies. For example, such as:
  • Neutropenia is of a cyclic nature.
  • Congenital immunodeficiency.
  • Agranulocytosis - complete or partial absence of neutrophils.
  • Myelokakeksia is a congenital inability of neutrophils to leave the bone marrow.
  • Dyskeratosis - a failure at the level of physiology, provoking a violation of the process of keratinization, affecting some cells of the epidermis.
• Infection, the localization of which was not timely established due to the fact that there was no response of the patient's body to irritation. But in the absence of a reaction, the inflammatory process itself is quite difficult. Has a high rate of spread, leading to death.
• Acute pharyngitis or urethritis.
• The cause of febrile neutropenia can be anaerobic microorganisms (for example, clostridia, Bacillus fragilis or Pseudomonas aeruginosa), as well as streptococci, staphylococci, microscopic fungi, Candida spp. Very rarely, but still there were cases when a "provocateur" of the pathology became cytomegalovirus or the herpes virus.

[2], [3], [4], [5]

Symptoms of the febrile neutropenia

The pathological condition manifests itself very quickly. The visual reaction, expressed by symptoms, can appear literally in a matter of hours. There are cases when neuropathy has developed within tens of minutes. Symptoms of febrile neutropenia:

• Against the backdrop of a sharp drop in the absolute number of neutrophils (this is less than 500) or granulocytes (this is less than 1000), there is a sharp increase in the patient's body temperature to 38 ° C or more.
• The total drop in the tone of the whole body, up to the asthenic syndrome of severe severity.
• A small tremor.
• Increasing heart rate.
• Reduced blood pressure. Such a manifestation can lead to a shock state or cardiovascular collapse.
• There may be severe sweating.

On the basis of the above, it can be summarized that febrile neutropenia is a symptomatology of exclusion, the diagnosis of pathology is established without pathognomonic symptoms. If in the future it is possible to determine the inflammatory focus, then the diagnosis is specified and adjusted. For example, it may be a developing sepsis of bacterial etiology or pneumonia.

[6], [7], [8]

Febrile neutropenia in cancer patients

Persons, whose history is burdened with oncology of any localization, are at risk for infection. In such patients, the percentage of purulent-inflammatory complications is much higher than in patients not burdened with such a pathology. This risk of infection in such patients largely depends on the nature of the cancer, its location, the severity of the course, as well as some factors predisposing to this. Based on this, febrile neutropenia in cancer patients is much more common than in patients with other diseases.

After carrying out bone marrow transplantation and immunosuppressive treatment, people diagnosed with hemoblastosis (tumors developing from hematopoietic cells) very often face granulocytopenia (a decrease in the number of neutrophils (granulocytes) of the blood). There is also a suppression of the process of seizure by special cells of blood and tissues (phagocytes), as well as the destruction of pathogens of infectious diseases and dead cells. This imbalance leads to a violation of humoral and / or cell defense. This significantly weakens the body, making it "easily accessible" to pathogenic microorganisms.

Febrile neutropenia in oncological patients with solid tumors is much less common, since immunosuppression after cytostatic therapy is not very pronounced. Granulocytopenia in this clinical picture appears for a short time, the probability of infection is insignificant, but it can not be completely excluded. The patient is able to become infected and as a result of natural obstruction: an artificial or inborn defect of anatomical membranes, the consequences of using shunts, catheters, prostheses, as well as inadequate functioning of central nervous system receptors. But such a defeat, as a rule, is not accompanied, however significant, by the infection

The longer and heavier the pathology, the higher the risk of infection. But the indicator considered can be influenced by the drugs chosen for therapy, the multiplicity of procedures for chemotherapeutic treatment.

A certain predominant localization of foci of infection in patients suffering from hemablastosis has been identified: about 34% of infections are caused by blood flow damage; 22% affects the pharynx, larynx and oral cavity. About 13% are respiratory diseases, mainly pneumonia, of which about a percent are sinusitis. The same percentage (13%) is the infection of soft tissues and skin epidermis. About seven percent - lesions of the gastrointestinal tract, five - phlebitis and intravascular catheters. About three percent falls on infection with the urinary system, all other cases account for about two percent. In more than half of the cases, it was not possible to determine the localization of the inflammatory focus.

[9], [10], [11], [12]

Diagnostics of the febrile neutropenia

Even with the slightest suspicion of this pathological condition, an urgent comprehensive examination is needed. Diagnosis of febrile neutropenia includes:

• Mandatory examination of urine and feces. The result of the analysis can show the presence of an inflammatory process in the patient's body (increased ESR, C-reactive protein).
• Clinical analysis of blood samples.
• Visual inspection, using the necessary tools, nasopharynx and throat.
• Laboratory testing of vomit and pulmonary or other sputum.
• Analysis of other biological fluids of the patient.

• Study to detect and establish the nature of bacteria isolated from the patient's material.
• Bacterioscopy is a method of examining liquid smears applied to a slide.
• Palpation of lymph nodes.
• Auscultation and X-ray of the lungs.
• Examination of the skin and visually accessible mucosa.

[13], [14], [15]

Treatment of the febrile neutropenia

In the event that the specialist has at least a slight suspicion of the pathology under consideration and the necessary diagnostic measures have been carried out, treatment of febrile neutropenia begins immediately, even in the absence of a specific etiology of the disease and eradication of the pathogen.

Empirical therapy with antibiotics is conducted. In the case of this diagnosis, preference is given to broad-spectrum antibiotics.

The classic of complex therapy is the use of an antifungal drug and three antibiotics. It is worth noting that this approach effectively covers almost the entire range of possible pathogens of infectious diseases. For example, such a complex of drugs equally effectively inhibits both streptococci, anaerobic microorganisms, and staphylococci.

If the causative agent is not yet known for certain, and, naturally, the sensitivity to a certain antibiotic is not defined, combinations are introduced into the initial protocol of treatment, an example of one of which is given below.

1. Medications related to the group of aminoglycosides (mainly prescribed antibiotics II or III generation). These include, for example, amikacin or gentamicin.

A highly active drug effectively inhibiting aerobic gram-negative bacteria, which adversely affects the bacterial synthesis of the protein, gentamicin is injected into the patient's intramuscular or intravenous route (the method of administration is determined by the treating doctor). The adult patient is once administered a medicine at the rate of 1 to 1.7 mg per kilogram of the patient's weight, the daily amount is from 3 to 5 mg per kilogram of weight. During the day, the medication is administered two to four times. Duration of treatment is from seven to ten days. For babies who are already two years old, the dose is calculated on the basis of: 3 - 5 mg / kg, broken down for a triple intake. Babies up to two years, the daily amount of the drug - from 2 to 5 mg / kg, divided into three inputs throughout the day. Just given birth and premature babies, the same daily dosage is divided into two doses.

You should not prescribe the drug when hypersensitivity to gentamicin and other antibiotics of the aminoglycoside group, as well as during pregnancy and during breastfeeding, with severe form of kidney failure or neuritis of the auditory nerve.

A powerful semisynthetic antibiotic amikacin is administered by drip or jet. Method of administration - intravenously or intramuscularly every 8 hours for 5 mg per kilogram of the weight of the baby or after 12 hours, but with a dosage of 7.5 mg per kilogram of the body weight of the patient. The maximum amount of a drug that can be used throughout the day is 15 mg per kilogram, but not more than 1.5 g per day. Duration of treatment in the case of intravenous administration is three to seven days, with intramuscular - from seven to ten days.

The starting amount of the drug for premature infants is 10 mg / kg, followed by 7.5 mg / kg. Reception is conducted after 18 hours or 24 hours. Newborns - the dosage is the same, and the interval between the inputs is 12 hours. Dose correction is required if the patient has a history of renal insufficiency.

It is not recommended to take this medication with hypersensitivity to gentamicin and other antibiotics of the aminoglycoside group, as well as during pregnancy and during breastfeeding, with severe form of kidney failure or neuritis of the auditory nerve.

2. In the initial protocol of treatment, inhibitor-protected aminopenicillin protective inhibitors are necessarily introduced. For example, you can use ampicillin-sulbactam or potassium amoxicillin-clavulanate.

The drug potassium amoxicillin-clavulanate is attributed to the inside, intramuscularly. The amount of medication prescribed is calculated in terms of amoxicillin. The regime and doses are taken individually. They depend on the severity of the pathology, the localization site, the name of the recognized pathogen and its sensitivity to chemical compounds. The dose is once prescribed depending on the age of the patient.

• newborns up to three months - a daily amount of 30 mg per kilogram of the baby's weight, separated by two inputs.
• children older than three months - a daily amount of 25 mg per kilogram of the baby's weight, divided into two injections (mild infection) or 20 mg / kg three times a day. With a serious infection of 45 mg / kg, divided into two doses or 40 mg / kg three times a day.
• adolescents older than 12 and adults: 0.5 g twice daily or 0.25 g three times throughout the day.

The maximum amount of administered per day is 0.6 g, for children less than 12 years - the daily maximum corresponds to 10 mg per kilogram of the patient's weight.

Contraindicated in the appointment of this drug for infectious mononucleosis, jaundice, phenylketonuria (a violation of the metabolism of amino acids, predominantly phenylalanine), dysfunction of baking and with individual intolerance to cephalosporins and other beta-lactam drugs.

3. It is mandatory to introduce a drug cephalosporin group III generation or carbapenems. Ceftazidime or ceftriaxone, meropenem or imipenem may be prescribed.

A potent broad-spectrum antibiotic, ceftriaxone, is given either intravenously or injected into the muscle.

The daily dosage for adult patients and adolescents over 12 years corresponds to numbers from 1 to 2 g once or 0.5-1 g twice a day (every 12 hours). The dose for a day should not be more than 4 g.

Newborns for up to two months, the drug is administered at a rate of 20 to 50 mg per kilogram of baby weight.

For small children who are not yet 12 years of age, the daily amount is calculated from 20 to 80 mg per kilogram of the weight of the baby. For children weighing more than 50 kg, a dose of adults is prescribed.

If the calculated dosage is taken at 50 mg / kg, ceftriaxone is injected with the infusion into the vein for half an hour. The duration of treatment is determined by the doctor, depending on the severity of the pathology.

The drug is not prescribed in case of hypersensitivity to the constituents of the medicine or other penicillins, cephalosporins, carbapenems.

Another optimal combination of drugs starting period can be called:

• One strong beta-lactam broad-spectrum antibiotic that belongs to one of the groups: cephalosporins of the third generation, aminopenicillin protective inhibitors or carbapenems.
• Similarly to the protocol proposed above, one drug of aminoglycosides is administered.
• And also fluoroquinolones III-IV generation. Of the chemical compounds belonging to these preparations, sparfloxacin or moxifloxacin can be mentioned.

Sparfloxacin is administered intravenously in the morning once. The first day - 0.4 g, then 0.2 g. The duration of the treatment course is appointed by the attending physician and is corrected from the severity of the pathology, but mainly lasts ten days. In the case of renal failure, the dosage of the drug is reduced.

Sparfloxacin is contraindicated in hypersensitivity to its components, in the absence of glucose-6-phosphate dehydrogenase in history, in case of predisposition to epileptic seizures, and acute renal failure.

Strongly antifungal medicines are necessarily used. It can be fluconazole or ketoconazole, in order to strengthen the pharmacodynamics of the antibacterial drugs used, it is recommended to introduce metronidazole in parallel.

Fluconazole is used in the form of capsules inside. Depending on the specific pathogen, the amount of the drug is assigned a slightly different dosage, but on average, as a rule, the starting number is 0.4 g, in the following the quantitative administration may decrease to 0.2 g or remain unchanged. The drug is administered once a day. Duration of therapy is six to eight weeks.

Do not prescribe a drug if the patient has a history of increased intolerance of the components of the drug, as well as women during pregnancy and lactation, children under the age of five.

The antiprotozoal and antimicrobial drug metronidazole is applied by dosage depending on the source of the lesion. The dose is given in digits of 0.25-0.5 g, taken twice a day. The duration of therapy is five to eight days. In case of medical necessity, treatment can be repeated by taking a break in three to four weeks. The daily amount of the drug administered can be from 0.75 to 1 g.

Metronidazole is not recommended for use if a history of the patient is diagnosed with leukopenia, liver dysfunction, organic damage to the central nervous system, individual intolerance to the constituents of the drug, the period of pregnancy and lactation of the newborn.

If there is a suspicion that enterococci or staphylococci are the causative agent of the inflammatory process, it is better to immediately label vancomycin in the protocol of treatment, replacing them with aminoglycoside drugs, as their combined use is undesirable, based on the fact that such a tandem enhances the nephrotoxicity of chemical compounds.

Vancomycin enters the patient's body into the vein. The adult patient receives 0.5 g every six hours or 1 g after 12 hours. To exclude the patient from provoking collapoid reactions, the volume should be injected approximately one hour in time. To small patients the daily dosage is appointed at the rate of 40 mg per kilogram of the child's weight. The rate of administration is similar. If the patient suffers from problems with excretion of urine (failure in the work of the kidneys), the dosage is adjusted taking into account the clearance of creatinine.

In some cases, the drug is attributed to the inside, then an adult daily amount of the drug is injected from 0.5 to 2 g divided into three to four doses, to small patients - 40 mg per kilogram of the child's weight, separated by three to four entries.

The drug in question is not recommended for use in neuritis of the auditory nerve, individual intolerance to the constituent of the drug, during the first trimester of pregnancy and during breastfeeding.

The greatest amount of the drug, allowed for admission during the day, should not be more than 4 g.

If it is justified as a source of pathology of the microflora of the Pseudomonas type, it is better to immediately prescribe the drug ticarcillin or the equivalent.

The method of taking and dosage of this medication is prescribed by the doctor, based on the overall clinical picture and age of the patient. It is inadmissible to administer the drug if a history of the patient is hypersensitive to ticarcillin or to beta-lactam antibiotics.

If the causative agent of pathology has been established, then therapy is adjusted based on this knowledge. Intensive three-day therapy was carried out, and the patient's condition did not improve - amphotericin B is administered. Aminoglycoside is prescribed to prevent the development of kidney damage.

In the case of diagnosing febrile neutropenia, the introduction of antipyretic drugs is not allowed. The consequence of their use changes the clinical picture of the disease, not allowing to assess the actual dynamics of therapy.

Prevention

Individuals with low levels of immune protection are at increased risk of invasion of pathogenic flora, which, depending on localization, causes various infectious and inflammatory diseases. To reduce the risk of injury, it is necessary, first of all, to take care of immunity. Necessary prevention of febrile neutropenia:

• It is necessary to correct the diet.
• In the diet must be present vegetables and fruits, rich in vitamins and minerals.
• Regular airing of dwellings and their wet cleaning.
• Complete rest.
• Minor physical activity and walking in the fresh air.
• It is necessary to minimize the contact of medical personnel who had symptoms of a catarrhal disease of a viral nature, with patients in whose anamnesis there is an immunodeficiency.
• Do not ignore the rules of general personal hygiene.
• Cleaning and washing of toilets, sinks and other surfaces should be carried out with the use of disinfectant solutions.
• Dishes of patients with a reduced immune system, after washing, should be treated in an oven with a temperature of 70 - 80 ° C.
• Before proceeding to processing or feeding, fresh fruits and vegetables must be thoroughly washed or heat-treated.
• Milk is better not to pasteurize, but sterilize.
• Prevention of febrile neutropenia with antimicrobial drugs.
• Selective decontamination with the use of adsorptive drugs (activated charcoal).
• Medicinal prophylaxis of febrile neutropenia after chemotherapy with the help of dicarbamine.

[16], [17], [18], [19], [20], [21],

Forecast

The immediate and long-term prognosis of febrile neutropenia directly depends on the severity of the lesion, the timeliness of adequate therapy. The prognosis of a benign nature of a mild degree of flow is favorable in almost all cases. If the pathology is caused by malignant neoplasm, weighed down by lymphocytopenia, the prognosis is less favorable.

About 21% of patients with this pathology, which developed against a background of cancers of different locations, expect an unfavorable prognosis.

Congenital febrile neutropenia can have a good prognosis only in the case of prophylactic therapy that lasts throughout life, or with a successful bone marrow transplant. An exception can only be a congenital neutropenia of a chronic nature and a benign etiology that has a low probability of infection.

[22], [23]