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Guidelines for the treatment of severe sepsis and septic shock: management of the infectious agent - diagnosis

Abstracts

Sepsis is a common and lethal condition that carries a substantial financial burden and is the primary cause of death in intensive care units. Early diagnosis and treatment of patients has been clearly shown to improve prognosis. Therefore, early diagnosis of infections and control of the primary infection site are fundamental to improving patients' prognosis. This guideline reviews the available evidence concerning the primary strategies for the diagnosis of infection


A sepse tem alta incidência, alta letalidade e custos elevados, sendo a principal causa de mortalidade em unidades de terapia intensiva. Está claramente demonstrado que pacientes reconhecidos e tratados precocemente tem melhor prognóstico. Nesse sentido, a abordagem precoce do agente infeccioso, tanto no sentido do diagnóstico como no controle do foco infeccioso são fundamentais para a boa evolução do paciente. A presente diretriz aborda as evidências disponíveis na literatura em relação às principais estratégias para esse diagnóstico.


SPECIAL ARTICLE

Guidelines for the treatment of severe sepsis and septic shock – management of the infectious agent - diagnosis

Décio DiamentI; Reinaldo SalomãoI; Otelo RigattoI; Brenda GomesI; Eliezer SilvaII; Noêmia Barbosa CarvalhoIII; Flavia Ribeiro MachadoIV

ISociedade Brasileira de Infectologia – SBI – Brazil

IIAssociação de Medicina Intensiva Brasileira – AMIB – Brazil

IIIAssociação Médica Brasileira – AMB – Brazil

IVInstituto Latino Americano de Sepse – ILAS – Brazil

Corresponding author

ABSTRACT

Sepsis is a common and lethal condition that carries a substantial financial burden and is the primary cause of death in intensive care units. Early diagnosis and treatment of patients has been clearly shown to improve prognosis. Therefore, early diagnosis of infections and control of the primary infection site are fundamental to improving patients' prognosis. This guideline reviews the available evidence concerning the primary strategies for the diagnosis of infection.

INTRODUCTION

Diagnosis of infection in septic patients is critical. Although the primary infection site is not always easily identified, it's, determination should be a primary concern in severe sepsis. Appropriate identification of the primary infection site allows the clinician to conduct specific tests, which can identify the causative organism.

Therapeutic management, including antimicrobial therapy, may be substantially different depending on the primary infection site. Thus, when the site is not identified, there is an increased risk of therapeutic error. Several studies have shown that inappropriate initial antibiotic regimen choices can lead to significantly increased mortality rates in septic patients.

In light of the available evidence in the literature, we will discuss approaches to the diagnosis of infection in those with severe infections and the measures to be adopted for site management. The most common severe infections will be discussed individually, as well as the scientifically validated therapeutic procedures for each.

OBJECTIVES

• To identify the best strategies for identifying infectious agents and to establish appropriate collection techniques;

• To evaluate the effectiveness and safety of infection site management in patients with severe sepsis and septic shock, such as removing catheters, early surgical resection and pleural effusion drainage;

• To review antimicrobial therapy recommendations for patients with sepsis, with respect to indication, early administration, dose adjustments, time of use, role of combined antibiotic therapy and de-escalation.

Description of the evidence collecting method

The Medline database (www.ncbi.nlm.nih.gov/pubmed) was searched using the following key words: inappropriate antimicrobial therapy; deescalating antimicrobial therapy; blood culture and sepsis or septic shock; blood culture and collection technique; skin antiseptics and blood cultures; blood culture contamination; skin preparation or skin or venipuncture site disinfection; changing needles and blood cultures; community acquired pneumonia and sputum culture; nosocomial or ventilator-associated pneumonia and sputum culture; lung biopsy or thoracoscopy and pneumonia or pneumonitis; catheter related bloodstream infection; urine culture and bacteriuria and catheter-associated urinary tract infections. This search provided 8,846 articles, of which 115 were selected.

Quality of evidence and recommendation

A: More consistent experimental or observational trials

B: Less consistent experimental or observational trials

C: Case reports (non-controlled trials)

D: Expert statement lacking critical evaluation based on consensus, physiology studies or animal models.

1. Is the causative agent identification relevant?

It is apparently obvious that the identification of the causative agent in sepsis is relevant. However, what is the available evidence that microbiological diagnosis methods have any impact on mortality from sepsis?

There is evidence that patients with sepsis treated with antibiotics appropriate to the culture-identified infective agent sensitivity data had lower mortality as compared to patients with inappropriate therapy (B).(1) Additionally, patients receiving inappropriate antibiotics who, when the culture results became available, had their antibiotic therapy tailored to the cultured agent sensitivity, had improved survival rates, although their outcomes were worse than the outcomes of patients who were initially treated appropriately. The earlier appropriate therapy is started, the better the patient's prognosis will be (B).(1-16)

Appropriate antibiotic therapy allows for de-escalation from empirical therapy to a more specific antibiotic regimen, which is suitable for organism sensitivity and may prevent the risk of selecting resistant bacteria (D).(17-20) Antibiotic de-escalation to more specific and less numerous antibiotic regimens reduces the overall cost of therapy (B).(21-26)

Recommendation

• Identification of the causative infectious agent should always be attempted, either using microbiological, immunological or molecular methods. This is fundamental for tailoring the antibiotic therapy to either cover organisms not covered by the initial empirical drug regimen or to reduce the spectrum of empirical antimicrobial therapy (de-escalation), therefore reducing cost and selective pressure.

2. Should blood cultures be collected for all severe sepsis patients, independent of the primary infectious site identification?

Cultures are the most important etiologic diagnostic tool available in clinical practice. Of the cultures to be collected, blood cultures play a primary role, as sepsis organisms may circulate continuously or intermittently. The organisms enter the blood stream from one or more infective foci, independent of their location, and may settle in other tissues forming secondary foci. Between 30 and 50% of severe sepsis patients have positive blood cultures. Pneumonia and intra-abdominal infections are those more frequently associated with secondary bacteremia (B).(27,28) Many cases of sepsis have no identified focus (D).(29) When a patient has an identified focus and this can be microbiologically analyzed (e.g., urine, sputum, cavity fluids, cerebrospinal fluid), these materials should be cultured concomitantly with blood cultures.

Although patients with severe sepsis and septic shock either with positive or negative blood cultures share the same risk factors and quite the same mortality (B),(30) the identification of the causative agent in the initial episode of sepsis, even in a later phase, has relevant implications for therapy. For example, the identification of the causative agent may result in de-escalation of antimicrobial therapy (i.e., the use of antibiotic therapy tailored to a more specific microbial spectrum) with a consequently reduced ecologic pressure over the hospital environment, thus reducing the possible selection of resistant bacteria and therapeutic costs.

Additionally, tailoring antibiotic therapy to the organism sensitivity data results in lower mortality (B)(1-16,21,22,24-26)(D).(17-20) Some studies have shown that running blood cultures in patients without risk factors hospitalized for community-acquired pneumonia may not be costeffective given the low rate of positive results (B)(31)(C)(32). However, in most severe cases of bacteremia, severe sepsis or septic shock, blood cultures could help with the identification of the causative agent and may consequently guide antibiotic therapy; despite this, the blood culture-identified agent may not be the agent causing pneumonia, especially if the patient has other sites of infection in addition to the lung foci (B).(33)

Recommendation

• Blood cultures and other suspected sites cultures are always recommended in patients with sepsis.

3. Does the technique for obtaining the blood culture impact its sensitivity and specificity?

The blood sample technique may affect blood culture sensitivity and specificity, providing either false-positive or false-negative results. Skin cleaning is relevant. In busy workplaces, such as intensive care units or emergency departments, the critical patient's condition may increase pressure to obtain a quick draw, causing inadequate use of aseptic techniques, thus resulting in blood culture contamination. Slow-acting antiseptics, such as Povidine or 70% alcohol, are only indicated if their effects can be allowed for two minutes. Faster acting antiseptics, such as chlorhexidine and iodine, which act within ten seconds, are more appropriate (A)(34-36)(B)(37)(C)(38)(D).(39) Specimens appropriately obtained by trained personnel provide better results with lower contamination rates (B).(40,41) After the blood is drawn, needles do not have to be replaced prior to blood culture bottle inoculation, both because this will not reduce contamination rates and because it increases the risks of accidental contamination, thus increasing costs to the hospital. Before the blood is inoculated into the blood culture bottle, the inoculation site (usually a rubber stopper) should be cleaned with antiseptics (B).(42-43)

Blood cultures should be preferably drawn from peripheral veins. Blood cultures drawn from catheters frequently result in contamination and are only suitable for diagnosing catheter-related bloodstream infections (CRBI). In such cases, blood is concomitantly drawn from both a peripheral vein and catheter, with the aim of checking whether the cultured organism is the same for both sites (B).(44-46) Blood cultures should be preferably drawn before antibiotic therapy is started, preventing the influence of antibiotics on the bacterial growth (false-negative). However, the dilution of antimicrobials in the culture medium may result in lower than the inhibitory concentrations, allowing for bacterial growth; therefore, blood cultures should be obtained even if the patient is already on antibiotics (B).(47) More than one sample should be obtained, up to three samples, with time intervals allowed between the drawings. The recommended volumes to be drawn depend on the blood culture method. Overall a 1:5 to 1:10 mL blood to culture medium ratio is recommended in adults. Bacteremia is generally intermittent, and the chance of culturing the organism increases with the number of samples drawn at given intervals. However, drawing more than three samples may be economically unfeasible and delay the initiation of empirical antibiotic therapy.

The time until drawing blood should be kept as short as possible, with the goal of starting empirical antibiotic therapy as soon as possible. Additionally, one study has shown that there is no benefit from using a drawing interval (B).(48) Given that the benefit of a time interval between sample draws has not been clearly shown and that this interval results in delayed initiation of antimicrobials, a time interval between the collection of samples is not recommended in the context of patients with severe sepsis. The blood to culture media ratio should comply with the blood culture system used, bearing in mind that different commercially available blood culture systems have different sensitivity and specificity levels (B).(49-54) The amount of blood to be drawn may impact the result: larger volumes improve the likelihood of pathogen detection, especially when bacteremia is intermittent or when there are lower numbers of circulating bacteria (B).(47,55-57)

With respect to interpreting culture results, the presence of skin flora bacteria (e.g., Staphylococcus epidermidis, Corynebacterium sp, Propionobacterium acnes, Bacillus sp, except B. anthracis) in a single sample suggest the presence of contaminants. The overall contamination risk is estimated to be 3% for one single sample. If these bacteria grow in one or more samples, the contamination likelihood drops to less than 1 out 1,000 (0.03 x 0.03 = 0.0009). Therefore, caution is advised in interpreting these blood culture results as a false positive. However, when growth of organisms as S. aureus, S. pyogenes, S. agalactiae, S. pneumoniae, E. coli and other enterobacteria, P. aeruginosa, B. fragilis and Candida sp are detected, these results are more likely to reflect bloodstream infection (B)(58-61)(D).(62-64)

Recommendation

• In patients with severe sepsis or septic shock, drawing three blood culture samples, adjusting the blood amount to the specified amount for each bottle, and preventing delayed antibiotic therapy are recommended. Appropriate skin antisepsis is recommended before the obtaining of the specimens; collection from catheters is discouraged, except for suspected catheter-associated bacteremia.

4. Do the respiratory specimens collecting techniques impact the diagnosis of community-acquired pneumonia?

Sputum collection for community-acquired pneumonia (CAP) diagnosis is a challenge due to the technical difficulties encountered in obtaining appropriate material. Generally, sputum from regular expectoration is contaminated by saliva or upper airways secretions, resulting in false-negative or false-positive results. Sputum analysis should be performed on purulent portions with at least ten or more epithelial cells and more than 25 polymorphonuclear leukocytes on low-power field (x100) microscopy (B)(65)(D).(66) Finding Gram-positive diplococci is specific (85 to 100%) for Pneumococcus but with variable sensitivity (15 to 100%) (A)(67)(B).(68,69)

There are many limitations to using sputum for the diagnosis of CAP. Many patients do not produce sputum, particularly during the initial phases. Even supervised by trained personnel, sputum collection is often inappropriate and frequently contaminated by either pathogenic or non-pathogenic upper airway bacteria, which may lead to interpretative errors. This is especially true in patients with chronic disease. Additional interpretation difficulties appear when results yealds Gram-negative bacteria. In addition, previous antibiotic therapy also impacts the results (D).(70)

Induced sputum has been used and mostly studied in acquired immunodeficiency syndrome (AIDS) patients with interstitial pneumonitis. Its diagnostic performance is perhaps more effective than non-induced sputum, although it is certainly less effective than bronchial lavage with or without bronchoscopy. In AIDS patients, this technique has a 13% to 55.5% sensitivity and a 98.6% specificity; these figures could be improved if stained P. jiroveci detection was replaced with immunofluorescence (B).(71,72) In patients who are HIV-positive or have AIDS, non-induced sputum for the diagnosis of CAP is as effective as in HIV-negative patients (B).(73)

In severe CAP patients with acute respiratory failure requiring intubation and mechanical ventilation, secretions collected via bronchial lavage without bronchoscopy and associated with semi-quantitative culture with a 10,000 colony forming units per milliliter threshold (104 CFU/mL) has good sensitivity, ranging from 58% to 83%, and is better than bronchoscopy lavage; additionally, it has the advantage of being non-invasive and easy to perform. This technique allows for the identification of the causative agent for the pneumonia in many cases, if it is performed early.

After identification of the causative agent, the antimicrobial therapy regimen may be tailored. Also, material from tracheal suction can be used for intubated patients with a 105-106 CFU/mL threshold.

Recommendation

• In severely ill patients, quantitative culture is recommended either from sputum, tracheal suction material or with/without bronchoscopy bronchial lavage fluid.

5. Do the respiratory specimens collecting techniques impact the ability to provide an etiological diagnosis for nosocomial mechanical ventilator associated pneumonia?

Nosocomial pneumonia diagnosis initially depends on judicious surveillance. The presence of infiltrates on chest radiography along with at least two of the following symptoms: fever or hypothermia, purulent expectoration and leukocytosis or leukopenia, has high sensitivity but low specificity for diagnosing ventilator-associated pneumonia (VAP) (B)(74)(D).(75)

Collecting specimens for VAP diagnosis may occur either by means of invasive techniques, such as bronchoscopy and bronchoalveolar lavage, or non-invasive techniques, such as tracheal suction. Studies have shown that both approaches have similar results with respect to mortality, hospital length of stay, antibiotic use and antibiotics regimen changes (A)(76-79)(B).(80) Both techniques should be semiquantitative to determine the number of colony forming units (CFU) in each sample. As tracheal sample specimens have an increased contamination risk, the cutoff point for a significant result should be above 105 or 106 CFU for tracheal suction, 104 CFU for bronchoalveolar lavage fluid or 103 CFU forprotected brushing.

Bilateral bronchoalveolar fluid sampling, either conducted with bronchoscopy or special probes, increases the diagnostic sensitivity if both lung samples show similar results. It should be noted that VAP is usually bilateral, and collecting specimens from both lungs increases the chance of diagnosing the involved organism. However, in unilateral cases, bilateral sampling can inoculate pathogenic organisms into the healthy lung (B).(81)

One should bear in mind that blood cultures have low sensitivity to detect the same organism isolated from sputum or bronchoalveolar lavage fluid cultures. Bacteremia is not able to predict complications, is not related to the length of hospital stay and is unable to detect patients with more severe disease. The isolation of an organism from blood culture does not necessarily mean that this is the VAP causative agent (B).(33)

Recommendation

• Where bronchoscopy is not available all of the time, tracheal suction for sputum collection is appropriate and has the same microbiological accuracy as bronchoscopic bronchoalveolar lavage fluid (B).(82-84) Semiquantitative tracheal suction material or bronchoscopic bronchial lavage fluid cultures are recommended, using different cutoff points.

6. Performing pulmonary biopsy is relevant to make the diagnosis of pneumonia and to determine the causative agent in terms of prognosis in both immunocompetent and immunocompromised patients?

Lung biopsy has been used to support the diagnosis of interstitial pneumonitis in immunocompromised patients who have an increased incidence of unusual pathogens, such as cytomegalovirus and Pneumocystis jiroveci. Interstitial infiltrates on chest radiography are a diagnostic challenge both in AIDS and cancer patients. The urgency represented by the acute respiratory failure, in connection with the deficient immune system, requires prompt diagnostic procedures and the initiation of empiric antibiotics. Infection with pathogens that usually do not grow in routine cultural media, in addition to the technical challenges of the not always available or feasible antigens, antibodies and nucleic acid detection methods, makes lung biopsy necessary to support the etiologic diagnosis of interstitial pneumonitis, with the goal being timely initiation of therapy. The identification of the causative organism allows for the selection of a more focused antimicrobial therapy regimen, avoiding adverse effects from multiple medications, decreasing costs and reducing mortality. The use of immunohistochemistry for anatomopathologic evaluation is very helpful for the early diagnosis of viral, fungal and parasitic diseases (B).(85) However, one study has compared the mortality of cancer patients undergoing pulmonary biopsy versus empirical antimicrobial therapy with broad spectrum antibiotics associated with erythromycin and sulfamethoxazole-trimethoprim. The mortality for both groups was the same but the biopsy group had more complications. Patients in the non-biopsy empiric therapy group and showing clinical deterioration underwent biopsy after a few days. The authors concluded that in cancer patients, especially those without neutropenia, lung biopsy may be reserved for cases not responding to broad spectrum antimicrobial therapy (A).(86)

In cases of interstitial lung disease, lung biopsy may be very helpful in patients showing no clinical improvement with the use of empirical antimicrobial therapy alone and in cases where is impossible to diagnose the causative agent by means of non-invasive methods. It is also fundamental for the diagnosis of lung neoplasms, for which clinical and radiological features resembling an infectious process are often seen, as in the case of lymphomas and carcinomatous lymphangitis (A).(87)

Pulmonary biopsy may be done via bronchoscopy (transbronchial), thoracoscopy or thoracotomy (“open-sky”). The indication for each approach is beyond the scope of these guidelines; however, it should be noted that transbronchial biopsy may entail more complications, including bleeding and pneumothorax. More recently, video-supported thoracoscopy has allowed for the use of an even less invasive procedure than thoracotomy (A)(88)(D).(89-92)

Recommendation

• Routine lung biopsy is not recommended for diagnosing infections of the lung parenchyma and should be reserved for cases where other diagnostic testing results were negative or when the patient clinically deteriorates despite broad spectrum antibiotic therapy. Cases of severe interstitial pneumonitis with acute respiratory failure are where biopsy is better indicated.

7. Do the different forms of diagnosing catheter related associated bloodstream infection have different sensitivity and specificity?

The diagnosis of catheter-related bloodstream infection (CRBI) is difficult to make due to the lack of correlation with the clinical picture, which is insufficient for diagnosis. CRBI can be defined in different ways. One definition would be that CRBI is the presence of bacteremia or fungemia in patients with an indwelling catheter, at least one positive peripheral blood culture with a clinical presentation of infection (i.e., fever, shivering, hypotension), with the absence of another source of infection but the catheter. This diagnosis would be confirmed by positive catheter tip culture with more than 15 colony forming units (CFU) on semiquantitative culture or more than 103 CFU on quantitative culture, and the same organism (both species and antibiogram) isolated from the catheter tip and peripheral blood. Another suggestive finding would be quantitative cultures simultaneously obtained from peripheral blood and catheter in a 5:1 CFU rate, respectively, or above two hours' differential time for organisms' growth between peripheral blood and catheter.

It should be noted that the first criterion implies that the catheter is removed and provides a retrospective diagnosis, which is not useful for the decision making process that must occur beforehand concerning whether to remove the catheter. These definitions are likely not applicable for antiseptics or antibiotics eluting catheters.

Fever and shivering, with or without hypotension, is very sensitive for detecting an infective process; however, it is not specific. Signs of infection at the catheter insertion site and signs of inflammation, pus and bacteremia are more specific. Isolation of skin flora organisms, such as S. aureus, S. epidermidis (coagulase negative), and Candida sp, support the CRBI diagnosis (D).(93,94)

As mentioned above, techniques for diagnosing CRBI include methods that involve either leaving the catheter in place or removing it. The classic method requires the catheter to be removed and an approximately 5 cm segment of the tip sent for semiquantitative culture using the Maki technique, which involves rolling the catheter segment over the culture media, or the quantitative technique, using the catheter sonication or vortex in fluid media. The Maki technique is sensitive for the detection of organisms colonizing the outer catheter surface, while the quantitative technique detects organisms colonizing both the outer and inner catheter surfaces. In short-term catheters, the semiquantitative technique has good sensitivity and specificity, as the organisms most frequently colonize the outer catheter surface. For long-term catheters, where the inner surface colonization is more important, the quantitative technique is better (B)(95,96)(D).(94)

Drawing small blood volumes from the catheter, followed by staining with Gram or acridine orange, are simple and promising methods. Their sensitivity ranges between 87 and 91%, while their specificity is between 94 and 97%, respectively. Intraluminal catheter brushing increases sensitivity and may result in more false-positive results; it may also cause higher embolization and bacteremia risks. Intraluminal catheter brushing was used in a CRBI diagnosis study; in the study, blood cultures were obtained pre- and post-brushing from the blood stream and the catheter. The catheter was then removed and cultured using the semiquantitative Maki technique. This technique was proven safe, provided the brush tip does not extend beyond the catheter tip. Bacteria counts from both peripheral blood culture and catheter were reduced after brushing perhaps due to removal of intraluminal biomass (B).(97)

There are limitations to the use of simultaneous peripheral blood and catheter cultures without quantification. Most catheters are colonized on their connections and in their lumen. Therefore, most positive cultures obtained from catheters reflect colonization rather than infection, especially when skin flora organisms are isolated, such as coagulase-negative staphylococci. However, this method has a high predictive value (98%).

Increased sensitivity and specificity for CRBI are achieved with simultaneous quantitative cultures obtained from the catheter and peripheral blood. Growth of at least 1,000 CFU on the culture from catheter specimens is highly specific (99%) for CRBI diagnosis; however, it has low sensitivity (20%). When associated with the same organism cultured on peripheral blood, its sensitivity is increased. Growth of organisms on the culture obtained from the catheter with a 5- to 10-fold CFU ratio in comparison with the peripheral blood culture is highly predictive of CRBI. Although being the most accurate method, simultaneous catheter and peripheral blood quantitative cultures are more expensive and complex (B)(95)(D).(93,94)

With automated blood culture techniques, the time it takes for the organism to grow can be monitored. Higher amounts of organisms in the blood lead to faster achievement of growth detection thresholds. When the differential growth time for catheter and peripheral bloods is above two hours, CRBI diagnosis sensitivity and specificity are high, 94 and 91%, respectively. However, these values are true only for long-term catheters, where intraluminal colonization is more frequent. For short-term catheters, results are poorer (B).(98-100)

Recommendation

• Catheter removal is recommended when it is suspected to be the primary source of infection in severe sepsis or septic shock patients. The tip should be sent for semiquantitative or quantitative culture. Techniques where the catheter is kept in place are not recommended in these cases given the risk of lacking the infectious site control. In other conditions, simultaneous peripheral and catheter bloods cultures, either quantitative or with differential growth time detection, may be used.

8. Should quantitative urine culture be used in the diagnosis of urinary tract infections?

The mere presence of bacteria detected in urine is not indicative of urinary tract infection and may reflect sample contamination from the genital flora. The use of quantitative urine culture in the diagnostic criteria for urinary tract infection was established based on pioneer trials (C).(101-103) In these trials, bacteriuria and urinary tract symptoms and signs in women were compared, with 100,000 colony forming units per milliliter of urine (CFU/mL) or greater being considered the infection threshold. Lower counts were considered contamination. However, symptomatic patients may have lower counts, and the value of urine culture results of less than 100,000 CFU/mL in diagnosing urinary tract infection depends on the patient's clinical features. For young and sexually active women with dysuria, pollakiuria and urinary urgency, 100 CFU/mL is significant (B)(104)(D).(105,106) Other conditions where urinary tract infection defining thresholds are lower than 100,000 CFU/mL include the following: young children, male patients, patients with urinary bladder catheters, recent antimicrobial use, diluted urine due to excessive fluid intake, urinary obstruction, pyuria and hematogenic pyelonephritis due to S. aureus or Candida sp. (D).(106,107)

In patients with vesical catheterization, the usual criterion is 100,000 CFU/mL. However, a lower threshold is suggested to be more appropriate especially in short-term catheterization where bacterial counts increase quickly. The incidence of vesical catheterization bacteriuria is between 3% and 10% per catheter day. As mean catheterization time is between 2 and 4 days, by the end of this time, 10 to 30% of the patients showed significant bacteriuria. After one month, i.e., long-term catheterization, more than 90% of the patients had bacteriuria. Approximately 15 to 20% of hospitalized patients undergo short periods of urinary bladder catheterization (B)(108)(D).(109)

The main complications are infection, urethritis and trauma. Most urinary catheterization-related infections are endogenous, arising from contamination with the patient's flora. Vesical catheters predispose patients to infection for several reasons, which are as follows: inner and outer catheter surface colonization (B),(110) biofilm formation (C),(111,112) increased bacterial adhesion to urethral epithelial cells (B),(113) inhibition of the antibacterial activity of polymorphonuclear leukocytes and promotion of urinary bladder residue (D).(114)

Independent risk factors for vesical catheterization-related bacteriuria are as follows: duration of the catheterization, urethral colonization with pathogenic bacteria, colonization of the collection bag connected to the urinary catheter, lack of antibiotic therapy, diabetes mellitus, female gender, abnormal serum creatinine, other uses in addition to urine volume measurement and manipulation errors (D)(109)(B).(115)

Recommendation

• Patients who are catheterized and asymptomatic should not undergo urine culture nor should prophylactic antibiotics or vesical wash be used to prevent catheter-related urinary infection. Signs and symptoms combined with risk factors for bacteriuria are crucial for reading quantitative urine culture results to make a diagnosis of urinary tract infection. In patients without vesical catheterization, it is recommend that urine collection be preceded by external genitalia cleaning, and women should be especially careful to separate the labia minora when voiding. The culture should be quantitative, although the positivity threshold is variable based on gender, symptoms and leukocyturia. For patients with indwelling vesical catheters, samples should be obtained using an aseptic technique, aspirating the urine from the catheter rather than from the collecting bag.

REFERENCES

  • 1. Harbarth S, Garbino J, Pugin J, Romand JA, Lew D, Pittet D. Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med. 2003;115(7):529-35.
  • 2. Vallés J, Rello J, Ochagavía A, Garnacho J, Alcalá MA. Community-acquired bloodstream infection in critically ill adult patients: impact of shock and inappropriate antibiotic therapy on survival. Chest. 2003;123(5):1615-24.
  • 3. Lodise TP Jr, Patel N, Kwa A, Graves J, Furuno JP, Graffunder E, et al. Predictors of 30-day mortality among patients with Pseudomonas aeruginosa bloodstream infections: impact of delayed appropriate antibiotic selection. Antimicrob Agents Chemother. 2007;51(10):3510-5.
  • 4. Tellado JM, Sen SS, Caloto MT, Kumar RN, Nocea G. Consequences of inappropriate initial empiric parenteral antibiotic therapy among patients with community-acquired intra-abdominal infections in Spain. Scand J Infect Dis. 2007;39(11-12):947-55.
  • 5. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589-96.
  • 6. Kang CI, Kim SH, Park WB, Lee KD, Kim HB, Kim EC, et al. Bloodstream infections caused by antibiotic-resistant gram-negative bacilli: risk factors for mortality and impact of inappropriate initial antimicrobial therapy on outcome. Antimicrob Agents Chemother. 2005;49(2):760-6.
  • 7. Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodovar A, Jimenez-Jimenez FJ, Perez-Paredes C, Ortiz-Leyba C. Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med. 2003;31(12):2742-51.
  • 8. Zaragoza R, Artero A, Camarena JJ, Sancho S, González R, Nogueira JM. The influence of inadequate empirical antimicrobial treatment on patients with bloodstream infections in an intensive care unit. Clin Microbiol Infect. 2003;9(5):412-8.
  • 9. Leone M, Bourgoin A, Cambon S, Dubuc M, Albanèse J, Martin C. Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome. Crit Care Med. 2003;31(2):462-7
  • 10. Zaidi M, Sifuentes-Osornio J, Rolón AL, Vázquez G, Rosado R, Sánchez M, et al. Inadequate therapy and antibiotic resistance. Risk factors for mortality in the intensive care unit. Arch Med Res. 2002;33(3):290-4.
  • 11. Hanon FX, Monnet DL, Sřrensen TL, Mřlbak K, Pedersen G, Schřnheyder H. Survival of patients with bacteraemia in relation to initial empirical antimicrobial treatment. Scand J Infect Dis. 2002;34(7):520-8.
  • 12. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest. 2000;118(1):146-55.
  • 13. Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115(2):462-74.
  • 14. Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik SD. The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med. 1998;244(5):379-86.
  • 15. Behrendt G, Schneider S, Brodt HR, Just-Nübling G, Shah PM. Influence of antimicrobial treatment on mortality in septicemia. J Chemother. 1999;11(3):179-86.
  • 16. Weinstein MP, Murphy JR, Reller LB, Lichtenstein KA. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. II. Clinical observations, with special reference to factors influencing prognosis. Rev Infect Dis. 1983;5(1):54-70.
  • 17. Niederman MS. The importance of de-escalating antimicrobial therapy in patients with ventilator-associated pneumonia. Semin Respir Crit Care Med. 2006;27(1):45-50.
  • 18. Turnidge J. Impact of antibiotic resistance on the treatment of sepsis. Scand J Infect Dis. 2003;35(9):677-82.
  • 19. Höffken G, Niederman MS. Nosocomial pneumonia: the importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU. Chest. 2002;122(6):2183-96.
  • 20. Alvarez-Lerma F, Grau S, Gracia-Arnillas MP. Gram-positive cocci infections in intensive care: guide to antibacterial selection. Drugs. 2006;66(6):751-68.
  • 21. Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis. 2006;42 Suppl 2:S82-9.
  • 22. Lemmen SW, Becker G, Frank U, Daschner FD. Influence of an infectious disease consulting service on quality and costs of antibiotic prescriptions in a university hospital. Scand J Infect Dis. 2001;33(3):219-21.
  • 23. Rosenthal VD, Guzman S, Migone O, Crnich CJ. The attributable cost, length of hospital stay, and mortality of central line-associated bloodstream infection in intensive care departments in Argentina: A prospective, matched analysis. Am J Infect Control. 2003;31(8):475-80.
  • 24. Teres D, Rapoport J, Lemeshow S, Kim S, Akhras K. Effects of severity of illness on resource use by survivors and nonsurvivors of severe sepsis at intensive care unit admission. Crit Care Med. 2002;30(11):2413-9.
  • 25. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303-10.
  • 26. Gutiérrez Zufiaurre MN, García-Rodríguez JA. [National multicenter survey: the use of intravenous antimicrobial agents]. Rev Esp Quimioter. 2006;19(4):349-56. Spanish.
  • 27. Opal SM, Garber GE, LaRosa SP, Maki DG, Freebairn RC, Kinasewitz GT, et al. Systemic host responses in severe sepsis analyzed by causative microorganism and treatment effects of drotrecogin alfa (activated). Clin Infect Dis. 2003;37(1):50-8.
  • 28. Brun-Buisson C, Doyon F, Carlet J. Bacteremia and severe sepsis in adults: a multicenter prospective survey in ICUs and wards of 24 hospitals. French Bacteremia-Sepsis Study Group. Am J Respir Crit Care Med. 1996;154(3 Pt 1):617-24.
  • 29. Russell JA. Management of sepsis. N Engl J Med. 2006;355(16):1699-713. Erratum in N Engl J Med. 2006;355(21):2267.
  • 30. Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, et al. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA. 1995;274(12):968-74.
  • 31. Campbell SG, Marrie TJ, Anstey R, Dickinson G, Ackroyd-Stolarz S. The contribution of blood cultures to the clinical management of adult patients admitted to the hospital with community-acquired pneumonia: a prospective observational study. Chest. 2003;123(4):1142-50.
  • 32. Chalasani NP, Valdecanas MA, Gopal AK, McGowan JE Jr, Jurado RL. Clinical utility of blood cultures in adult patients with community-acquired pneumonia without defined underlying risks. Chest. 1995;108(4):932-6.
  • 33. Luna CM, Videla A, Mattera J, Vay C, Famiglietti A, Vujacich P, Niederman MS. Blood cultures have limited value in predicting severity of illness and as a diagnostic tool in ventilator-associated pneumonia. Chest. 1999;116(4):1075-84.
  • 34. Schifman RB, Pindur A. The effect of skin disinfection materials on reducing blood culture contamination. Am J Clin Pathol. 1993;99(5):536-8.
  • 35. Little JR, Murray PR, Traynor PS, Spitznagel E. A randomized trial of povidone-iodine compared with iodine tincture for venipuncture site disinfection: effects on rates of blood culture contamination. Am J Med. 1999;107(2):119-25.
  • 36. Mimoz O, Karim A, Mercat A, Cosseron M, Falissard B, Parker F, et al. Chlorhexidine compared with povidone-iodine as skin preparation before blood culture. A randomized, controlled trial. Ann Intern Med. 1999;131(11):834-7.
  • 37. Strand CL, Wajsbort RR, Sturmann K. Effect of iodophor vs. iodine tincture skin preparation on blood culture contamination rate. JAMA. 1993;269(8):1004-6.
  • 38. King TC, Price PB. An evaluation of iodophors as skin antiseptics. Surg Gynecol Obstet. 1963;116:361-5.
  • 39. Malani A, Trimble K, Parekh V, Chenoweth C, Kaufman S, Saint S. Review of clinical trials of skin antiseptic agents used to reduce blood culture contamination. Infect Control Hosp Epidemiol. 2007;28(7):892-5.
  • 40. Surdulescu S, Utamsingh D, Shekar R. Phlebotomy teams reduce blood-culture contamination rate and save money. Clin Perform Qual Health Care. 1998;6(2):60-2.
  • 41. Weinbaum FI, Lavie S, Danek M, Sixsmith D, Heinrich GF, Mills SS. Doing it right the first time: quality improvement and the contaminant blood culture. J Clin Microbiol. 1997;35(3):563-5.
  • 42. Spitalnic SJ, Woolard RH, Mermel LA. The significance of changing needles when inoculating blood cultures: a meta-analysis. Clin Infect Dis. 1995;21(5):1103-6.
  • 43. Schifman RB, Strand CL, Meier FA, Howanitz PJ. Blood culture contamination: a College of American Pathologists Q-Probes study involving 640 institutions and 497134 specimens from adult patients. Arch Pathol Lab Med. 1998;122(3):216-21.
  • 44. Bryant JK, Strand CL. Reliability of blood cultures collected from intravascular catheter versus venipuncture. Am J Clin Pathol. 1987;88(1):113-6.
  • 45. DesJardin JA, Falagas ME, Ruthazer R, Griffith J, Wawrose D, Schenkein D, et al. Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer. Ann Intern Med. 1999;131(9):641-7.
  • 46. Everts RJ, Vinson EN, Adholla PO, Reller LB. Contamination of catheter-drawn blood cultures. J Clin Microbiol. 2001;39(9):3393-4.
  • 47. Schermer CR, Sanchez DP, Qualls CR, Demarest GB, Albrecht RM, Fry DE. Blood culturing practices in a trauma intensive care unit: does concurrent antibiotic use make a difference? J Trauma. 2002;52(3):463-8.
  • 48. Li J, Plorde JJ, Carlson LG. Effects of volume and periodicity on blood cultures. J Clin Microbiol. 1994;32(11):2829-31.
  • 49. Frank U, Malkotsis D, Mlangeni D, Daschner FD. Controlled clinical comparison of three commercial blood culture systems. Eur J Clin Microbiol Infect Dis. 1999;18(4):248-55.
  • 50. Murray PR, Hollick GE, Jerris RC, Wilson ML. Multicenter comparison of BACTEC 9050 and BACTEC 9240 blood culture systems. J Clin Microbiol. 1998;36(6):1601-3.
  • 51. Pohlman JK, Kirkley BA, Easley KA, Washington JA. Controlled clinical comparison of Isolator and BACTEC 9240 Aerobic/F resin bottle for detection of bloodstream infections. J Clin Microbiol. 1995;33(10):2525-9.
  • 52. Morello JA, Leitch C, Nitz S, Dyke JW, Andruszewski M, Maier G, et al. Detection of bacteremia by Difco ESP blood culture system. J Clin Microbiol. 1994;32(3):811-8.
  • 53. Wilson ML, Weinstein MP, Reimer LG, Mirrett S, Reller LB. Controlled comparison of the BacT/Alert and BACTEC 660/730 nonradiometric blood culture systems. J Clin Microbiol. 1992;30(2):323-9.
  • 54. Washington JA. An international multicenter study of blood culture practices. The International Collaborative Blood Culture Study Group. Eur J Clin Microbiol Infect Dis. 1992;11(12):1115-28.
  • 55. Weinstein MP, Mirrett S, Wilson ML, Reimer LG, Reller LB. Controlled evaluation of 5 versus 10 milliliters of blood cultured in aerobic BacT/Alert blood culture bottles. J Clin Microbiol. 1994;32(9):2103-6.
  • 56. Isaacman DJ, Karasic RB, Reynolds EA, Kost SI. Effect of number of blood cultures and volume of blood on detection of bacteremia in children. J Pediatr. 1996;128(2):190-5.
  • 57. Kellogg JA, Manzella JP, Bankert DA. Frequency of low-level bacteremia in children from birth to fifteen years of age. J Clin Microbiol. 2000;38(6):2181-5.
  • 58. Weinstein MP, Towns ML, Quartey SM, Mirrett S, Reimer LG, Parmigiani G, Reller LB. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis. 1997;24(4):584-602.
  • 59. Weinstein MP, Reller LB, Murphy JR, Lichtenstein KA. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev Infect Dis. 1983;5(1):35-53.
  • 60. Bates DW, Lee TH. Rapid classification of positive blood cultures. Prospective validation of a multivariate algorithm. JAMA. 1992;267(14):1962-6.
  • 61. Bates DW, Goldman L, Lee TH. Contaminant blood cultures and resource utilization. The true consequences of false-positive results. JAMA. 1991;265(3):365-9.
  • 62. MacGregor RR, Beaty HN. Evaluation of positive blood cultures. Guidelines for early differentiation of contaminated from valid positive cultures. Arch Intern Med. 1972;130(1):84-7.
  • 63. Rupp ME, Archer GL. Coagulase-negative staphylococci: pathogens associated with medical progress. Clin Infect Dis. 1994;19(2):231-43; quiz 244-5. Review.
  • 64. Weinstein MP. Blood culture contamination: persisting problems and partial progress. J Clin Microbiol. 2003;41(6):2275-8.
  • 65. Murray PR, Washington JA. Microscopic and bacteriologic analysis of expectorated sputum. Mayo Clin Proc. 1975;50(6):339-44.
  • 66. Mandell LA, Marrie TJ, Grossman RF, Chow AW, Hyland RH. Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society. The Canadian Community-Acquired Pneumonia Working Group. Clin Infect Dis. 2000;31(2):383-421.
  • 67. Reed WW, Byrd GS, Gates RH Jr, Howard RS, Weaver MJ. Sputum gram's stain in community-acquired pneumococcal pneumonia. A meta-analysis. West J Med. 1996;165(4):197-204.
  • 68. Rein MF, Gwaltney JM Jr, O'Brien WM, Jennings RH, Mandell GL. Accuracy of Gram's stain in identifying pneumococci in sputum. JAMA. 1978;239(25):2671-3.
  • 69. Aderaye G. The value of sputum gram stain in the diagnosis of pneumococcal pneumonia. Ethiop Med J. 1994;32(3):167-71.
  • 70. San Pedro GS, Campbel GD Jr. Limitations of diagnostic testing in the initial management of patients with community-acquired pneumonia. Semin Respir Infect. 1997;12(4):300-7. Review.
  • 71. Cruciani M, Marcati P, Malena M, Bosco O, Serpelloni G, Mengoli C. Meta-analysis of diagnostic procedures for Pneumocystis carinii pneumonia in HIV-1-infected patients. Eur Respir J. 2002;20(4):982-9.
  • 72. Miller RF, Kocjan G, Buckland J, Holton J, Malin A, Semple SJ. Sputum induction for the diagnosis of pulmonary disease in HIV positive patients. J Infect. 1991;23(1):5-15.
  • 73. Cordero E, Pachón J, Rivero A, Girón-González JA, Gómez-Mateos J, Merino MD, et al. Usefulness of sputum culture for diagnosis of bacterial pneumonia in HIV-infected patients. Eur J Clin Microbiol Infect Dis. 2002;21(5):362-7.
  • 74. Fàbregas N, Ewig S, Torres A, El-Ebiary M, Ramirez J, de La Bellacasa JP, et al. Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies. Thorax. 1999;54(10):867-73.
  • 75. Valencia M, Torres A. Ventilator-associated pneumonia. Curr Opin Crit Care. 2009;15(1):30-5. Review.
  • 76
    Canadian Critical Care Trials Group. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med. 2006;355(25):2619-30.
  • 77. Ruiz M, Torres A, Ewig S, Marcos MA, Alcón A, Lledó R, et al. Noninvasive versus invasive microbial investigation in ventilator-associated pneumonia: evaluation of outcome. Am J Respir Crit Care Med. 2000;162(1):119-25.
  • 78. Sanchez-Nieto JM, Torres A, Garcia-Cordoba F, El-Ebiary M, Carrillo A, Ruiz J, et. al. Impact of invasive and noninvasive quantitative culture sampling on outcome of ventilator-associated pneumonia: a pilot study. Am J Respir Crit Care Med. 1998;157(2):371-6. Erratum in Am J Respir Crit Care Med 1998;157(3 Pt 1):1005.
  • 79. de Jaeger A, Litalien C, Lacroix J, Guertin MC, Infante-Rivard C. Protected specimen brush or bronchoalveolar lavage to diagnose bacterial nosocomial pneumonia in ventilated adults: a meta-analysis. Crit Care Med. 1999;27(11):2548-60.
  • 80. Wood AY, Davit AJ 2nd, Ciraulo DL, Arp NW, Richart CM, Maxwell RA, Barker DE. A prospective assessment of diagnostic efficacy of blind protective bronchial brushings compared to bronchoscope-assisted lavage, bronchoscope-directed brushings, and blind endotracheal aspirates in ventilator-associated pneumonia. J Trauma. 2003;55(5):825-34.
  • 81. Jackson SR, Ernst NE, Mueller EW, Butler KL. Utility of bilateral bronchoalveolar lavage for the diagnosis of ventilator-associated pneumonia in critically ill surgical patients. Am J Surg. 2008;195(2):159-63.
  • 82. Mentec H, May-Michelangeli L, Rabbat A, Varon E, Le Turdu F, Bleichner G. Blind and bronchoscopic sampling methods in suspected ventilator-associated pneumonia. A multicentre prospective study. Intensive Care Med. 2004;30(7):1319-26.
  • 83. Leo A, Galindo-Galindo J, Folch E, Guerrero A, Bosques F, Mercado R, Arroliga AC. Comparison of bronchoscopic bronchoalveolar lavage vs blind lavage with a modified nasogastric tube in the etiologic diagnosis of ventilator-associated pneumonia. Med Intensiva. 2008;32(3):115-20.
  • 84. Flanagan PG, Findlay GP, Magee JT, Ionescu A, Barnes RA, Smithies M. The diagnosis of ventilator-associated pneumonia using non-bronchoscopic, non-directed lung lavages. Int Care Med. 2000;26(1):20-30.
  • 85. Solans EP, Garrity ER Jr, McCabe M, Martinez R, Husain AN. Early diagnosis of cytomegalovirus pneumonitis in lung transplant patients. Arch Pathol Lab Med. 1995;119(1):33-5.
  • 86. Browne MJ, Potter D, Gress J, Cotton D, Hiemenz J, Thaler M, et. al. A randomized trial of open lung biopsy versus empiric antimicrobial therapy in cancer patients with diffuse pulmonary infiltrates. J Clin Oncol. 1990;8(2):222-9.
  • 87. Potter D, Pass HI, Brower S, Macher A, Browne M, Thaler M, et. al. Prospective randomized study of open lung biopsy versus empirical antibiotic therapy for acute pneumonitis in nonneutropenic cancer patients. Ann Thorac Surg. 1985;40(5):422-8.
  • 88. Ayed AK, Raghunathan R. Thoracoscopy versus open lung biopsy in the diagnosis of interstitial lung disease: a randomised controlled trial. J R Coll Surg Edinb. 2000;45(3):159-63.
  • 89. Luh SP, Liu HP. Video-assisted thoracic surgery--the past, present status and the future. J Zhejiang Univ Sci B. 2006;7(2):118-28.
  • 90. Boutin C, Loddenkemper R, Astoul P. Diagnostic and therapeutic thoracoscopy: techniques and indications in pulmonary medicine. Tuber Lung Dis. 1993;74(4):225-39.
  • 91. Loddenkemper R. Thoracoscopy--state of the art. Eur Respir J. 1998;11(1):213-21.
  • 92. Tassi GF, Davies RJ, Noppen M. Advanced techniques in medical thoracoscopy. Eur Respir J. 2006;28(5):1051-9.
  • 93. O'Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG, et al. Guidelines for the prevention of intravascular catheter-related infections. Centers for Disease Control and Prevention. MMWR Recomm Rep. 2002;51(RR10):1-29.
  • 94. Nicoletti C, Carrara D, Richtmann R, organizadores. Infecção relacionada ao uso de cateteres vasculares. 3Ş ed. São Paulo: Associação Paulista de Estudos e Controle de Infecção Hospitalar; 2005.
  • 95. Safdar N, Fine JP, Maki DG. Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection. Ann Intern Med. 2005;142(6):451-66.
  • 96. Siegman-Igra Y, Anglim AM, Shapiro DE, Adal KA, Strain BA, Farr BM. Diagnosis of vascular catheter-related bloodstream infection: a meta-analysis. J Clin Microbiol. 1997;35(4):928-36.
  • 97. Dobbins BM, Kite P, Catton JA, Wilcox MH, McMahon MJ. In situ endoluminal brushing: a safe technique for the diagnosis of catheter-related bloodstream infection. J Hosp Infect. 2004;58(3):233-7.
  • 98. Blot F, Nitenberg G, Chachaty E, Raynard B, Germann N, Antoun S, et. al. Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet. 1999;354(9184):1071-7.
  • 99. Gaur AH, Flynn PM, Giannini MA, Shenep JL, Hayden RT. Difference in time to detection: a simple method to differentiate catheter-related from non-catheter-related bloodstream infection in immunocompromised pediatric patients. Clin Infect Dis. 2003;37(4):469-75.
  • 100. Quilici N, Audibert G, Conroy MC, Bollaert PE, Guillemin F, Welfringer P, et al. Differential quantitative blood cultures in the diagnosis of catheter-related sepsis in intensive care units. Clin Infect Dis. 1997;25(5):1066-70.
  • 101. Marple CD. The frequency and character of urinary tract infections in an unselected group of women. Ann Intern Med. 1941;14(12):2220-39.
  • 102. Kass EH. Asymptomatic infections of the urinary tract. Trans Assoc Am Physicians. 1956;69:56-64.
  • 103. Merritt AD, Sanford JP. Sterile-voided urine culture; an evaluation in 100 consecutive hospitalized women. J Lab Clin Med. 1958;52(3):463-70.
  • 104. Hooton TM, Scholes D, Stapleton AE, Roberts PL, Winter C, Gupta K, et al. A prospective study of asymptomatic bacteriuria in sexually active young woman. N Engl J Med. 2000;343(14):992-7.
  • 105. Stamm WE. Protocol for diagnosis of urinary tract infection: reconsidering the criterion for significant bacteriuria. Urology. 1988;32(2 Suppl):6-12.
  • 106. Woods GL. Specimen collection and handling for diagnosis of infectious diseases. In: Henry JB, editor. Clinical diagnosis and management by laboratory methods.19th ed. Philadelphia: Saunders; c1996 p. 1311-31.
  • 107. Platt R. Quantitative definition of bacteriuria. Am J Med. 1983;75(1B):44-52.
  • 108. Garibaldi RA, Burke JP, Dickman ML, Smith CB. Factors predisposing to bacteriuria during indwelling urethral catheterization. N Engl J Med. 1974;291(5):215-9.
  • 109. Warren JW. Catheter-associated urinary tract infections. Infect Dis Clin North Am. 1997;11(3):609-22.
  • 110. Garibaldi RA, Burke JP, Britt MR, Miller MA, Smith CB. Meatal colonization and catheter-associated bacteriuria. N Engl J Med. 1980;303(6):316-8.
  • 111. Cox AJ, Hukins DW, Sutton TM. Infection of catheterised patients: Bacterial colonisation of encrusted Foley catheters shown by scanning electron microscopy. Urol Res. 1989;17(6):349-52.
  • 112. Nickel JC, Gristina AG, Costerton JW. Electron microscopy study of an infected Foley catheter. Can J Surg. 1985;28(1):50-1, 54.
  • 113. Daifuku R, Stamm WE. Bacterial adherence to bladder uroepithelial cells in catheter-associated urinary tract infection. N Engl J Med. 1986;314(19):1208-13.
  • 114. Zimmerli W, Lew PD, Waldvogel FA. Pathogenesis of foreing body infection. Evidence for a local granulocyte defect. J Clin Invest. 1984;73(4):1191-200.
  • 115. Platt R, Polk BF, Murdock B, Rosner B. Risk factors for nosocomial urinary tract infections. Am J Epidemiol. 1986;124(6):977-85.
  • Autor correspondente:
    Flavia Ribeiro Machado
    R. Napoleão de Barros 75 – 5º andar
    CEP: 04024-900- São Paulo (SP), Brasil.
    Fone: (11) 5576-4069
    E-mail:
  • Publication Dates

    • Publication in this collection
      01 Aug 2011
    • Date of issue
      June 2011

    History

    • Reviewed
      Dec 2010
    • Received
      July 2009
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