Initial antibiotic therapy for sepsis

The initial antibiotic treatment of sepsis, the Department of Critical Care Medicine, the Fourth Affiliated Hospital of Hebei Medical University, translated by Yunpeng Li, edited by Zhu Guijun, edited by Zhu Guijun.
Abstract: Sepsis is a common consequence of infection and has a mortality rate of >25%
.

Community-acquired sepsis is the most common, and hospital-acquired infections are more lethal
.

The most common site of infection is the lungs, followed by abdominal infections, catheter-related blood gas infections and urinary tract infections
.

Gram-negative infections are more common than Gram-positive infections, and sepsis can also be caused by fungal and viral pathogens
.

In order to reduce mortality, immediate, experimentally-based broad-spectrum therapy is necessary for patients with severe sepsis and/or shock, but this will lead to the overuse of antibiotics and the development of resistance to pathogens.
At the same time, it is committed to downgrading and antibiotic management
.

Biomarkers such as procalcitonin can provide support for antibiotic use decisions, and can identify patients with a low likelihood of infection, and in some cases can guide the duration of antibiotic treatment
.

Sepsis may involve drug-resistant pathogens, and newer antibiotics usually need to be considered
.

Background Sepsis is a common and life-threatening disease in the ICU and requires timely and effective antibiotic treatment
.

The purpose of this review is to determine the prevalence of sepsis, the possible pathogens, and the best method of antibiotic treatment
.

Effective treatment must be balanced with the need to avoid overuse of broad-spectrum drugs, so there must be a commitment to antibiotic management
.

Using experts on this subject, we reviewed the literature related to antibiotic management in sepsis and recommended key management principles
.

Epidemiology of sepsis, the site of infection and the pathogen.
Sepsis is a life-threatening organ dysfunction syndrome caused by the host's unbalanced response to infection.
The mortality rate exceeds 25%.
It has been recognized as the top priority for global health.

.

Most sepsis is community-acquired, and the progression may be insidious, making diagnosis very difficult
.

The prognosis depends on the early use of broad-spectrum antibiotics and effective source control
.

Sepsis affects 1.
7 million adults in the United States each year, with nearly 270,000 deaths, with 19.
4 million to 31.
5 million cases and 5.
3 million deaths worldwide each year
.

A global study reported that the global incidence of sepsis dropped from 60 million cases in 1990 to 49 million cases in 2017, a decrease of 18.
8%
.

However, from 2012 to 2018, the number of sepsis-related medical insurance hospitalizations increased from 811,644 to 1,136,889, and the increase in hospitalization and subsequent care costs increased from US$27.
7 billion to US$41.
5 billion
.

The mortality rate after 6 months of septic shock is still high at 60%, and the mortality rate for severe sepsis is 36%
.

Bacterial infection is the most common cause, and viruses and fungi may occur in patients with comorbidities and immunosuppression
.

The most common lesions in hospitalized patients are lower respiratory tract infections, followed by intra-abdominal, blood flow, intravascular infections and urinary tract infections
.

The main bloodstream isolates include Staphylococcus aureus, Escherichia coli, Klebsiella, Pseudomonas aeruginosa, Enterococcus, Streptococcus and coagulase-negative Staphylococcus
.

In the expanded prevalence rate of intensive care infection (EPIC III) study involving 15,000 ICU patients from 88 countries, 65% of patients had at least one microbial culture positive, of which Gram-negative pathogens were the most common (67%, n =3540), including Klebsiella
.

Escherichia coli, Pseudomonas, Enterobacteriaceae, Proteus, Stenotrophomonas, Serratia and Acinetobacter
.

Gram-positive microorganisms (37%, n=1946)
.

Staphylococcus aureus
.

Streptococcus pneumoniae and Enterococcus are the most common, and Candida and Aspergillus are common fungal microorganisms (16%, n=864)
.

Compared with infection with other microorganisms, specific multi-drug-resistant pathogens (vancomycin-resistant enterococcus (OR=2.
41), Klebsiella resistant to β-lactam antibiotics (OR=1.
29), resistant to specific multi-drug-resistant pathogens Carbapenem Acinetobacter (OR=1.
40)] independently has a higher risk of death
.

In a study of 1072 patients with mainly community sepsis, 61% of the patients received some medical care, including recent antibiotics, chemotherapy, wound care, and dialysis
.

Or underwent surgery within 30 days before the onset of sepsis, 57% of the patients were found to have the pathogen
.

The 30-day mortality rate of patients with potential comorbidities such as liver cirrhosis (OR=3.
59), immunosuppression (OR=2.
52), and vascular disease (OR=1.
54) increased
.

In another study that included 2.
2 million hospitalizations, Rhee and colleagues reported that community-acquired sepsis was more common than hospital-acquired sepsis (12.
1%, n=11534) (87.
9%, n=83620) , But the mortality rate of hospital-acquired sepsis is higher (OR=2.
1; 95%CI, 2.
0–2.
2)
.

In a meta-analysis of 51 studies from developing and developed countries (including neonatal ICU), the mortality rate of patients with hospital-acquired sepsis was 52.
3% (95% CI: 43.
4-61.
1%)
.

Worldwide, men’s age-standardized sepsis-related mortality is higher than women’s (164.
2:134.
1/100,000).
Diarrhea and lower respiratory tract infections rank first and second among common causes of sepsis-related deaths
.

The importance of early appropriate and timely treatment Timely administration of appropriate antibiotic treatment (that is, with in vitro activity against pathogenic pathogens) is the cornerstone of the management of serious ICU infections
.

Observational, prospective and retrospective studies support the use of appropriate empiric antibiotics in sepsis and septic shock
.

A prospective study in 1999 evaluated 2,000 ICU patients and showed that inappropriate initial antibiotic therapy is associated with higher mortality
.

These findings have been confirmed in a meta-analysis, showing that compared with patients with severe bacterial infections who received appropriate and inappropriate antibiotics at an early stage, the mortality rate was reduced (OR 0.
44, 95% CI 0.
38–0.
50) and the length of hospital stay was significant Shortened, hospitalization costs are correspondingly reduced
.

Antifungal treatments for Candida blood infections are similarly related
.

A retrospective cohort study of 21,608 adults with bloodstream infections from 131 hospitals in the United States found that 4165 (19%) received inconsistent empiric antibiotic therapy (based on in vitro testing of blood culture isolates).
This was independently associated with an increased risk of death (adjusted odds ratio 1.
46 [95% CI, 1.
28–1.
66])
.

A retrospective cohort analysis of bloodstream infections with severe sepsis and septic shock found that the number of treatments (NNT) required to prevent death of a patient with appropriate initial antibiotic treatment was 4.
0 (95% CI, 3.
7- 4.
3)
.

The pathogen-specific NNT after prevalence adjustment is: multi-drug-resistant (MDR) bacteria (NNT=20), while Candida albicans (NNT=34), methicillin-resistant Staphylococcus aureus (MRSA; NNT=38) ) And Pseudomonas aeruginosa (NNT=38)
.

The randomized prospective MERINO trial compares the therapeutic effects of piperacillin-tazobactam and meropenem on severe bloodstream infections caused by ceftriaxone-insensitive Escherichia coli or Klebsiella pneumoniae, and supports appropriate early treatment
.

The non-inferiority of the piperacillin-tazobactam group cannot be determined.
Of the 187 patients randomized to the piperacillin-tazobactam group, 23 (12.
3%) died within 30 days and were randomized to receive meropenem 7 of the 191 patients (3.
7%) (risk difference, 8.
6%))
.

Delays in giving appropriate treatment may be due to delays in infection recognition and antibiotic administration, but the best timing of treatment depends on the population studied
.

A recent review indicated that a reasonable time frame should not be later than 3 to 5 hours after infection, but patients with septic shock should be treated immediately
.

The management of early and appropriate treatment must be balanced with unnecessary antibiotic use, especially the use of broad-spectrum drugs, in the absence of confirmed infections, the mortality associated with this practice is too high, and the colonization of antibiotic-resistant pathogens And the risk of infection increases
.

Therefore, the use of rapid broad-spectrum empirical treatment, especially in emergency situations, must have a downgrading commitment, that is, once clinical and microbiological data are available, shorten the course of treatment, reduce broad-spectrum treatment and reduce drugs (Figure 1)
.

Biomarkers to guide the treatment of sepsis The clinical and biological markers of sepsis are neither sensitive nor specific, especially in elderly patients and immunocompromised patients.
The choice between starting and stopping antibiotic therapy in ICU patients has Challenging
.

Intensive care physicians are always looking for biomarkers to determine when to safely delay antibiotic treatment for patients with suspected infections
.

In 1998, the biomarker is defined as "normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic index intervention is objectively measured and evaluated characteristics"
.

Ideally, sepsis biomarkers should distinguish true sepsis from other inflammatory diseases in a timely, cost-effective manner, and be able to monitor response to treatment and guide when to start and safely stop treatment
.

Sepsis activates a variety of biochemical and immune pathways, and releases various molecules that may serve as biomarkers
.

Many promising biomarkers have been evaluated.
In randomized controlled studies of antibiotic management, C-reactive protein (CRP) and procalcitonin are the most commonly evaluated
.

In view of the heterogeneity and complexity of sepsis, no biomarker has sufficient accuracy to distinguish sepsis from other non-infectious causes of systemic inflammation, and biomarkers can only be used as an auxiliary means of clinical judgment , Used to determine when to start antibiotics
.

However, the information gathered by combining several biomarkers may be valuable
.

The development of molecular biology, including "omics", will enable better development of sepsis biomarkers, and their usefulness will increase by integrating them into biological scores
.

Several host-responsive gene expression assays have been developed
.

SeptiCyteTM LB (Immunexpress, Seattle, WA) has been approved by the US FDA to distinguish sepsis from non-infectious systemic inflammation in a heterogeneous cohort of 249 adult intensive care patients
.

The use of biomarkers to guide individualized antibiotic treatment duration in sepsis patients seems to be more intuitive than fixed treatment duration
.

In a meta-analysis of patient levels centered on the management of antibiotics guided by procalcitonin (11 trials), the use of continuous measurement facilitated the early discontinuation of antibiotics and shortened the treatment time (2,252 procalcitonin guided patients The treatment time was 9.
3 days, while the treatment time of 2230 control patients was 10.
4 days; p<0.
001), and the mortality rate was significantly reduced under the guidance of procalcitonin
.

Importantly, CRP has been shown to have the same effect as calcitonin in reducing the use of antibiotics in the medical population dominated by sepsis patients
.

Biomarker decision support for sepsis management to guide treatment duration is more valuable than determining when to start antibiotic treatment
.

Biomarkers with high negative predictive value and clinical evaluation can help rule out infections and determine the need for immediate antibiotic treatment
.

Antibiotic treatment: Principles of use and new drugs Although appropriate treatment refers to the use of pathogen-sensitive antimicrobial agents, it is also necessary to give the correct dose at the best time to penetrate the infected site
.

This must be done without excessive use, otherwise drug resistance may develop on a global scale and lead to antibiotic resistance in the individual’s own intestinal flora, which is usually the source of ICU-acquired infections
.

The best use of antibiotics includes avoiding underdose while preventing adverse reactions related to overdose
.

In severe sepsis, an initial high-loading dose is required to "fill" higher than the usual volume of distribution-approximately 1.
5 times the standard dose
.

Then the drug is administered according to the drug clearance rate
.

Level 1 and Level 2 evidence indicate that double coverage of Gram-negative infections is not necessary
.

However, some people still give large doses of aminoglycoside drugs and another drug to patients infected in the ICU to ensure a sufficiently wide coverage and optimize the rapid killing of pathogens
.

Commonly used ICU antibiotics have different killing properties
.

For β-lactam drugs, the best effect is related to the time to exceed the minimum inhibitory concentration (MIC) of the target pathogen; high daily doses are best carried out by continuous or extended infusion
.

Although this can improve the efficacy by maintaining a high concentration of trough, especially in the presence of drug resistance, not all data support this situation
.

For the treatment of aminoglycoside drugs (a dose- or concentration-dependent antibiotic), daily high-dose (or extended time interval in case of renal insufficiency) should be used
.

Quinolones also have a dose-dependent lethality.
Although they are administered at intervals, they should also have higher doses
.

The increase in renal clearance usually occurs in young patients without renal dysfunction, so a higher dose than the standard daily dose is required to avoid sub-therapeutic concentrations
.

In renal replacement therapy, there may be insufficient medication and overdose, but higher doses of β-lactam drugs may be a better choice to prevent under medication
.

Therapeutic drug monitoring can be used as an adjunct to the administration of most antibiotics
.

When choosing antibiotics, the site of infection is important
.

Lipophilic antibiotics (such as quinolones) can guarantee high concentrations in all tissues
.

Hydrophilic antibiotics (such as aminoglycosides) do not penetrate well into tissues (lungs, etc.
), but stay in the extravascular space, although β-lactams are more permeable than aminoglycosides
.

In the past, patients who used antibiotics were easily colonized by bacteria resistant to these drugs, and traveling to areas with a high incidence of drug-resistant organisms could lead to intestinal colonization of these endemic bacteria
.

In addition, treatment in the ICU with a high local drug resistance rate can also easily lead to drug-resistant pathogen infection
.

Some new antibiotics can be used to treat serious infections caused by resistant Gram-positive and Gram-negative bacteria
.

Cefoloxan-tazobactam is active against multi-drug resistant (MDR) Pseudomonas aeruginosa
.

Other newer drugs, ceftazidime-avibactam, imipenem-ribactam, meropenem-vabobactam, and cefadil can be used in patients with risk factors for drug-resistant pathogens, and these pathogens are resistant to these drugs Especially sensitive
.

For those Enterobacteriaceae that are resistant to carbapenem, ceftazidime-avibactam, imipenem-ribactam, and meropenem-vabobactam may be the most effective
.

For organisms that produce metal-β-lactamases, ceftazidime-avibactam and cefadil are good choices
.

In the future, phage therapy may be a treatment option for sepsis that needs to be studied
.

Pneumonia: initial empirical treatment of CAP, HAP, and VAP for severe community-acquired pneumonia (CAP)
.

For patients with no risk factors for MRSA or Pseudomonas aeruginosa (PSA) infection, the current recommended initial empirical therapy is (a) β-lactams plus cyclic lactones or (b) β-lactams plus breathing With fluoroquinolones (FQ), both therapies are acceptable, but more evidence favors β-lactams/macrolides
.

Although the evidence supporting these recommendations is based on observational studies, a meta-analysis and systematic review found that compared with β-lactams/FQ, the mortality rate of β-lactam/macrolide treatment is Improved, especially for severe CAP
.

There are not enough data to recommend the use of FQ monotherapy or β-lactams plus doxycycline in severe CAP
.

Patients with risk factors for MRSA or PSA may have been characterized as medically associated pneumonia (HCAP) in the past, but this claim has been abandoned
.

A number of studies have shown that HCAP risk factors may not necessarily predict the presence of resistant bacteria, and coverage of these organisms does not improve clinical outcomes
.

The 2019 ATS/IDSA guidelines recommend that CAP patients with risk factors for these pathogens should be covered by empirical MRSA and/or PSA, and if the culture result is negative, then downgraded treatment
.

The best risk factors for MRSA and PSA infections are the previous growth of these pathogens, as well as recent hospitalization and parenteral antibiotic exposure (within 90 days)
.

Facts have proved that it is difficult to develop an effective scoring system to accurately predict the risk of these pathogens, and it is also difficult to develop locally effective risk factors
.

In severe CAP, empirical MRSA and/or PSA coverage and downgrade processing have proven to be a safe strategy
.

However, a recent study found that in the case of negative cultures, the overall rate of degradation is very low, which provides an opportunity to improve the use of antibiotics
.

The recommended empirical treatment for MRSA pneumonia includes vancomycin or linezolid
.

PSA treatment includes piperacillin/tazobactam, cefepime, ceftazidime, aztreonam, meropenem, or imipenem
.

Newer drugs may also have a role
.

Hospital and ventilator-acquired pneumonia (HAP, VAP)
.

It is recommended to use the local antibiotic map to guide the use of empirical antibiotics
.

All patients with VAP should receive empirical treatment of Staphylococcus aureus and PSA/Gram-negative bacteria.
For patients with risk factors, additional consideration should be given to resistant bacteria
.

These factors include antibiotics used within 90 days, septic shock or ARDS, hospitalization for at least 5 days in the past 90 days, and the need for acute renal replacement therapy, although not all studies have validated these risk factors
.

For patients with at least one of the above risk factors, as well as the local MRSA prevalence is unknown or Staphylococcus aureus isolates> 10-20%, it is recommended to use MRSA treatment coverage for VAP
.

For VAP patients with at least one risk factor for resistant organisms, as well as the local resistance to a single anti-pseudomonas drug, the prevalence of gram-negative bacteria resistance is unknown, or the gram-negative bacteria isolates >10 % Of cases, it is recommended to use two different classes of anti-pseudomonas drugs
.

The treatment of HAP is the same as that of VAP
.

The guidelines support empirical treatment of drug-resistant pathogens in high-risk patients, and if the culture result is negative, then downgrading treatment will be followed
.

For all high-risk patients, the initial empirical treatment plan should include methicillin-sensitive Staphylococcus aureus and PSA/gram-negative bacteria (such as piperacillin/tazobactam, cefepime, imipenem , Meropenem, ceftizide/tazobactam)
.

The recommended treatment regimen for MRSA and resistant PSA is similar to the treatment regimen for severe CAP described above
.

Intra-abdominal infection Complex intra-abdominal infection (cIAI)-refers to the spread of the disease beyond the initial focus of infection, such as diffuse peritonitis after diverticulitis-usually diagnosed before entering the ICU, but may also be during ICU hospitalization Occurs, usually after surgery
.

cIAI is usually multi-microbial, with aerobic bacteria and anaerobes
.

Among Gram-negative pathogens, Enterobacter is the most common, and non-fermentative pathogens such as Pseudomonas or Acinetobacter are not as common as respiratory or bloodstream infections
.

Enterococci are particularly prevalent in cIAI in critically ill patients-they account for about half of Gram-positive isolates
.

But the cultivation of anaerobic bacteria may be difficult
.

Although during surgery to control the source of infection (percutaneous drainage or open surgery), the source of infection is only sampled at a later stage, but empiric antibiotic treatment should not be delayed
.

Blood culture should be performed, but the significance of sampling the abdominal drainage tube is limited
.

Empiric treatment should cover a wide range of pathogens, such as a broad-spectrum β-lactam/β-lactamase inhibitor combination or carbapenem drugs to adapt to the local environment
.

However, in the treatment of enterococci, some strains may be insensitive to β-lactam antibiotics, especially after recent exposure to such drugs, empirical treatment with glycopeptides or oxazolidinones should be considered
.

When using empiric carbapenems for treatment, the sensitivity of enterococci must be confirmed
.

Severe patients with cIAI often have a variety of risk factors for aggressive candidiasis.
It is generally recommended that empirical antifungal therapy be given to patients with the most severe disease
.

In a recent global study, 13% of patients involved fungus, and two-thirds of them were isolated from Candida albicans
.

Depending on the severity of the disease, local epidemiology and previous exposure to antifungal drugs, azole or echinocandin drugs can be used empirically
.

Controlling the source of infection is very important and should be implemented as quickly as possible in logistical support
.

If the infection is local and there is no persistent contamination of the abdomen, percutaneous drainage is preferred
.

Empiric treatment of bacteremia: Nearly half of the sepsis patients admitted to the hospital remain culture-negative
.

However, in culture-positive patients, microbiological data from blood provides an important opportunity to modify the treatment
.

In bacterial infections, there are three empirical windows before a clear drug susceptibility result
.

(1) Treatment under the guidance of syndromes, (2) Treatment under the guidance of Gram staining morphology, and (3) Treatment under the guidance of pathogens
.

The hospital’s antibacterial spectrum, for each specific drug-bacteria combination, can help select empirical antibiotic treatment before obtaining drug susceptibility results in pathogen-guided treatment (empirical window 3)
.

Recently, because rapid pathogen identification methods such as matrix absorption laser desorption/ionization time of flight (MALDI-TOF) have surpassed rapid drug susceptibility testing methods, this window has been expanded to an earlier point in time
.

Before window 3, the weighted incidence rate hospital antimicrobial spectrum can provide the overall drug susceptibility rate of all gram-negative bacteria, which can be used to guide the treatment of experience window 2
.

Compiling historical susceptibility information by syndrome is more challenging, but it can provide local guidelines for the empirical treatment of syndromes (window 1), such as central venous catheter-related bloodstream infection (CLBSI) and intra-abdominal/hepatobiliary infections
.

In order to make the antibiotic map operable, we need to know the target coverage threshold of empiric therapy
.

In a physician survey, the preferred threshold for mild sepsis was 80%, and severe sepsis was 90%
.

If the 90% minimum threshold is used, for infections like VAP and CLABSI, we will probably need to recommend toxic (such as aminoglycosides), retention (such as carbapenem), or toxic and retention (such as cola) for almost every patient.
Set) to further promote the emergence of antibiotic resistance
.

The solution is to use the known predictors of antibiotic resistance to individualize empirical antibiotic therapy, so that we can use narrow-spectrum monotherapy when the conditions are met, thereby limiting the broad-spectrum combination therapy to the most People who need it (Figure 2)
.

The decision support model for empiric treatment of gram-negative bacteremia can incorporate risk factors for drug resistance (patient demographics, recent hospital exposure, recent antibiotic use, previous microbiological culture results), and promote antibiotic development Degrade quickly without affecting the time to proper treatment
.

As discussed for pneumonia, the patient’s previous microbiological results provide powerful information for predicting drug resistance in current infections
.

For Staphylococcus aureus bacteremia, if the previous MRSA monitoring swab result is positive, anti-MRSA empirical treatment must be used
.

For Gram-negative bacteremia, if Gram-negative bacteria resistant to a particular drug are found in the past year, the antibiotic should be excluded
.

Treatment of fungal sepsis Invasive fungal infection (IFI) as a cause of ICU sepsis is increasing and is associated with a mortality rate of 40% to 60%
.

Epidemiological data, risk factors, prediction criteria, scores, microbiology data, and biomarkers can help identify patients with fungal sepsis
.

Fungi account for about 5% of all sepsis cases
.

Candida is the main pathogen.
It is the sixth to tenth largest pathogen of bloodstream infections.
It usually manifests as candidiasis or deep candidiasis
.

One-third of candidaemia occurs in the ICU, and 25% to 35% of patients with candidaemia will develop sepsis or septic shock
.

Pneumocysticercosis, cryptococcosis, histoplasmosis, invasive aspergillosis, mucormycosis, fusarium, penicillosis, and sedosporosis occasionally occur disseminated infections and sepsis
.

Candida is a normal component of the microbiota of the skin, gastrointestinal tract, urethra, and vagina.
When isolated from non-sterile body parts, it is difficult to distinguish between settled and infected strains
.

As an opportunistic pathogen, Candida is unlikely to cause infection if there is no significant change in the integrity of the microbiota, skin or mucous membranes, or host defense system
.

In ventilator ICU patients with normal immune function, Candida albicans isolated from lower respiratory tract specimens almost always indicates colonization rather than infection
.

Candida colonization index (the ratio of positive to negative cultures for screening of body parts) of 0.
5 or higher may increase the possibility of invasive candidiasis and may lead to preventive or empirical treatment
.

The risk factors for invasive candidiasis are non-specific and similar to bacterial infections (previous colonization, broad-spectrum antibiotic therapy, intravenous access devices, parenteral nutrition, diabetes, renal insufficiency, hemodialysis, abdominal surgery, pancreatitis , Neutropenia, solid organ transplantation and immunosuppressive therapy)
.

A scoring system based on a combination of risk factors, underlying diseases, and clinical characteristics shows a high (>90%) negative predictive value for IFI, which may help rule out invasive candidiasis
.

The culture-based IFI diagnostic test is not sensitive, and the cycle is long, leading to a delay in the initiation of targeted antifungal therapy
.

30% to 50% of patients with candidiasis and 80% to 90% of patients with primary deep candidiasis have negative blood cultures
.

The sensitivity and specificity of non-culture-based tests, the sensitivity of mannan/anti-mannan antibody, β-D-glucan and polymerase chain reaction is between 75% and 95%, Candida albicans buds The sensitivity and specificity of the tube assay are between 45% and 95%
.

The T2 Candida group looks promising in early clinical trials
.

In view of the high mortality associated with IFI, especially in patients with weakened immunity, timely initiation of preventive or empirical antifungal therapy is essential
.

The clinical situation (main site of infection, host immune status), local epidemiology, microbiology and fungal biomarker data, previous antifungal drugs and potential drug interactions will guide the choice of antifungal therapy
.

Echinocandins are the drugs of choice for the treatment of invasive candidiasis
.

However, the emergence of Candida acanthensis, Candida glabrata and Candida auris is worrying
.

Lipid formulations of triazole drugs or amphotericin B are the first choice for the treatment of fungal infections
.

Downgrading treatment will depend on the response to the initial treatment and the results of the training
.

Proper source control (emptying the collection, removing the catheter or prosthetic device as much as possible) is an important part of management
.

Conclusion The treatment of suspected sepsis requires thoughtful and personalized care
.

For patients who are most likely to develop infections, serious illnesses, and/or shock, initial empirical treatment should be performed immediately
.

When choosing a specific empiric antibiotic treatment, the possible infection sites and common pathogens in these sites should be considered, and modified by considering the patient’s specific drug resistance risk factors and local microbiology knowledge
.

Although timely and appropriate treatment is necessary to reduce mortality, it must be promised at the same time that treatment will be downgraded once we have obtained training and a series of clinical and laboratory data, because indiscriminate use of broad-spectrum empirical treatment is antibiotic resistant.
The driving force of medicine
.

Table 1 summarizes the main management recommendations
.

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