When are combinations of antibiotics clinically useful?

Antimicrobial resistance is a global crisis. Prescribing antibacterial combinations may be one way of reducing the development of resistance in target pathogens, as in the treatment of tuberculosis. Combinations may be useful for ascertaining synergy, broadening antimicrobial cover to reduce the risk of non-susceptibility, antimicrobial stewardship reasons, and immune modulation. The current research literature and/or prevailing global standards of clinical care suggest that combination therapy may be advantageous in: severe community-acquired pneumonia; severe hospital-acquired or ventilator-associated pneumonia or when there is a high risk of resistance in hospital-acquired or ventilator-associated pneumonia; multi-drug or extensively drug-resistant Gram-negative infections; and severe group A streptococcal infections. In other situations, combinations may be harmful. Overall, outside of tuberculosis, combination antibacterial therapy is likely to improve outcomes only in specific circumstances and there is little evidence to suggest that this prevents the development of bacterial resistance. Further high-quality research is essential.

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Effect of hospital-acquired ventilator-associated pneumonia on mortality of severe community-acquired pneumonia

Journal of Critical Care ◽

10.1016/s0883-9441(99)90003-5 ◽

1999 ◽

Vol 14 (1) ◽

pp. 12-19 ◽

Cited By ~ 8

Author(s):

Olivier Leroy ◽

Jérome Guilley ◽

Hughes Georges ◽

Philippe Choisy ◽

Benoit Guery ◽

...

Keyword(s):

Community Acquired Pneumonia ◽

Ventilator Associated Pneumonia ◽

Severe Community Acquired Pneumonia ◽

Hospital Acquired

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Avoiding ventilator-associated pneumonia: Curcumin-functionalized endotracheal tube and photodynamic action

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2006759117 ◽

2020 ◽

Vol 117 (37) ◽

pp. 22967-22973

Author(s):

Amanda C. Zangirolami ◽

Lucas D. Dias ◽

Kate C. Blanco ◽

Carolina S. Vinagreiro ◽

Natalia M. Inada ◽

...

Keyword(s):

Endotracheal Tube ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Ventilator Associated Pneumonia ◽

Hospital Acquired Infection ◽

Hospital Acquired Infections ◽

Hospitalization Costs ◽

Hospital Acquired

Hospital-acquired infections are a global health problem that threatens patients’ treatment in intensive care units, causing thousands of deaths and a considerable increase in hospitalization costs. The endotracheal tube (ETT) is a medical device placed in the patient’s trachea to assist breathing and delivering oxygen into the lungs. However, bacterial biofilms forming at the surface of the ETT and the development of multidrug-resistant bacteria are considered the primary causes of ventilator-associated pneumonia (VAP), a severe hospital-acquired infection for significant mortality. Under these circumstances, there has been a need to administrate antibiotics together. Although necessary, it has led to a rapid increase in bacterial resistance to antibiotics. Therefore, it becomes necessary to develop alternatives to prevent and combat these bacterial infections. One possibility is to turn the ETT itself into a bactericide. Some examples reported in the literature present drawbacks. To overcome those issues, we have designed a photosensitizer-containing ETT to be used in photodynamic inactivation (PDI) to avoid bacteria biofilm formation and prevent VAP occurrence during tracheal intubation. This work describes ETT’s functionalization with curcumin photosensitizer, as well as its evaluation in PDI against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. A significant photoinactivation (up to 95%) against Gram-negative and Gram-positive bacteria was observed when curcumin-functionalized endotracheal (ETT-curc) was used. These remarkable results demonstrate this strategy’s potential to combat hospital-acquired infections and contribute to fighting antimicrobial resistance.

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A Literature Review on Hospital-Acquired Pneumonia (HAP), Community-Acquired Pneumonia (CAP), and Ventilator-Associated Pneumonia (VAP)

Gene Cell and Tissue ◽

10.5812/gct.116869 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Pedram Bolboli Zade ◽

Abbas Farahani ◽

Mohammadreza Riyahi ◽

Ali Laelabadi ◽

Ali Salami Asl ◽

...

Keyword(s):

Risk Factors ◽

Community Acquired Pneumonia ◽

Specific Information ◽

Ventilator Associated Pneumonia ◽

Artificial Airway ◽

Control And Prevention ◽

Hospital Acquired Pneumonia ◽

And Gender ◽

Hospital Acquired ◽

Common Infection

: One of the most dangerous respiratory diseases is pneumonia, one of the ten leading causes of death globally. Hospital-acquired pneumonia (HAP) is a common infection in hospitals, which is the second most common nosocomial infection and causes inflammation parenchyma. In Community-acquired pneumonia (CAP), we have various risk factors, including age and gender, and also some specific risk factors. Ventilator-associated pneumonia (VAP) is one of the deadliest nosocomial infections. According to the Centers for Disease Control and Prevention, VAP is pneumonia that develops about 48 hours of an artificial airway. Bacterial, viral, parasitic, primordial, and other species can cause these diseases. We discuss bacterial factors. Our goal is to gather information about HAP, CAP, and VAP to give people specific information. In this study, these three issues have been examined together, but in similar studies, each of them has been examined separately, and our type of study will be more helpful in diagnosis and treatment.

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Disease Risk and Mortality Prediction in Intensive Care Patients with Pneumonia. Australian and New Zealand Practice in Intensive Care (ANZPIC II)

Anaesthesia and Intensive Care ◽

10.1177/0310057x0503300116 ◽

2005 ◽

Vol 33 (1) ◽

pp. 101-111 ◽

Cited By ~ 17

Author(s):

R. J. Boots ◽

J. Lipman ◽

R. Bellomo ◽

D. Stephens ◽

R. F. Heller

Keyword(s):

Intensive Care ◽

New Zealand ◽

Clinical Signs ◽

Community Acquired Pneumonia ◽

Ventilator Associated Pneumonia ◽

Invasive Ventilation ◽

Non Invasive ◽

Non Invasive Ventilation ◽

Hospital Acquired Pneumonia ◽

Hospital Acquired

This study of ventilated patients investigated pneumonia risk factors and outcome predictors in 476 episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14 intensive care units within Australia and New Zealand. For community acquired pneumonia, mortality increased with immunosuppression (OR 5.32, CI 95% 1.58–17.99, P<0.01), clinical signs of consolidation (OR 2.43, CI 95% 1.09–5.44, P=0.03) and Sepsis-Related Organ Failure Assessment (SOFA) scores (OR 1.19, CI 95% 1.08–1.30, P<0.001) but improved if appropriate antibiotic changes were made within three days of intensive care unit admission (OR 0.42, CI 95% 0.20–0.86, P=0.02). For hospital-acquired pneumonia, immunosuppression (OR 6.98, CI 95% 1.16–42.2, P=0.03) and non-metastatic cancer (OR 3.78, CI 95% 1.20–11.93, P=0.02) were the principal mortality predictors. Alcoholism (OR 7.80, CI 95% 1.20–17.50, P<0.001), high SOFA scores (OR 1.44, CI 95% 1.20–1.75, P=0.001) and the isolation of “high risk” organisms including Pseudomonas aeruginosa, Acinetobacter spp, Stenotrophomonas spp and methicillin resistant Staphylococcus aureus (OR 4.79, CI 95% 1.43–16.03, P=0.01), were associated with increased mortality in ventilator-associated pneumonia. The use of non-invasive ventilation was independently protective against mortality for patients with community-acquired and hospital-acquired pneumonia (OR 0.35, CI 95% 0.18–0.68, P=0.002). Mortality was similar for patients requiring both invasive and non-invasive ventilation and non-invasive ventilation alone (21% compared with 20% respectively, P=0.56). Pneumonia risks and mortality predictors in Australian and New Zealand ICUs vary with pneumonia type. A history of alcoholism is a major risk factor for mortality in ventilator-associated pneumonia, greater in magnitude than the mortality effect of immunosuppression in hospital-acquired pneumonia or community-acquired pneumonia. Non-invasive ventilation is associated with reduced ICU mortality. Clinical signs of consolidation worsen, while rationalising antibiotic therapy within three days of ICU admission improves mortality for community-acquired pneumonia patients.

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The Spectrum of Practice in the Diagnosis and Management of Pneumonia in Patients Requiring Mechanical Ventilation. Australian and New Zealand Practice in Intensive Care (ANZPIC II)

Anaesthesia and Intensive Care ◽

10.1177/0310057x0503300115 ◽

2005 ◽

Vol 33 (1) ◽

pp. 87-100 ◽

Cited By ~ 16

Author(s):

R. J. Boots ◽

J. Lipman ◽

R. Bellomo ◽

D. Stephens ◽

R. F. Heller

Keyword(s):

Intensive Care ◽

New Zealand ◽

Antibiotic Prescription ◽

Antibiotic Use ◽

Community Acquired Pneumonia ◽

Diagnostic Methods ◽

Ventilator Associated Pneumonia ◽

Third Generation ◽

Hospital Acquired Pneumonia ◽

Hospital Acquired

This study of ventilated patients investigated current clinical practice in 476 episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14 intensive care units (ICUs) within Australia and New Zealand. Diagnostic methods and confidence, disease severity, microbiology and antibiotic use were assessed. All pneumonia types had similar mortality (community-acquired pneumonia 33%, hospital-acquired pneumonia 37% and ventilator-associated pneumonia 24%, P=0.15) with no inter-hospital differences (P=0.08–0.91). Bronchoscopy was performed in 26%, its use predicted by admission hospital (one tertiary: OR 9.98, CI 95% 5.11–19.49, P<0.001; one regional: OR 6.29, CI 95% 3.24–12.20, P<0.001), clinical signs of consolidation (OR 3.72, CI 95% 2.09–6.62, P<0.001) and diagnostic confidence (OR 2.19, CI 95% 1.29–3.72, P=0.004). Bronchoscopy did not predict outcome (P=0.11) or appropriate antibiotic selection (P=0.69). Inappropriate antibiotic prescription was similar for all pneumonia types (11–13%, P=0.12) and hospitals (0–16%, P=0.25). Blood cultures were taken in 51% of cases. For community-acquired pneumonia, 70% received a third generation cephalosporin and 65% a macrolide. Third generation cephalosporins were less frequently used for mild infections (OR 0.38, CI 95% 0.16–0.90, P=0.03), hospital-acquired pneumonia (OR 0.40, CI 95% 0.23–0.72, P<0.01), ventilator-associated pneumonia (OR 0.04, CI 95% 0.02–0.13, P<0.001), suspected aspiration (OR 0.20, CI 95% 0.04–0.92, P=0.04), in one regional (OR 0.26, CI 95% 0.07–0.97, P=0.05) and one tertiary hospital (OR 0.14, CI 95% 0.03–0.73, P=0.02) but were more commonly used in older patients (OR 1.02, CI 95% 1.01–1.03, P=0.01). There is practice variability in bronchoscopy and antibiotic use for pneumonia in Australian and New Zealand ICUs without significant impact on patient outcome, as the prevalence of inappropriate antibiotic prescription is low. There are opportunities for improving microbiological diagnostic work-up for isolation of aetiological pathogens.

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