**8.3. Vancoplus**

While we look for HAP/VAP due to Gram-positive bacteria, methicillin-resistant *S. aureus* is a big concern and empirical antibiotic therapy should cover MRSA whenever factors increase the likelihood of MRSA. Now, MRSA is not confined to western countries only. A network of microbiology laboratories (Indian Network for Surveillance of Antimicrobial Resistance—INSAR) at premier medical colleges and hospitals in India was formed with support from the World Health Organization. In an article published in 2013, INSAR reported that MRSA prevalence in India is to the tune of 40% which shows that MRSA is a significant problem for India too.

Vancoplus is a novel AAE of ceftriaxone and vancomycin along with l-arginine as adjuvant caters to all types of mixed infection especially MRSA, VRSA, VISA, and hGISA [43].

been observed that when two non-compatible drugs are administered due to medical urgency with due precautions, still there exists certain degree of degradation of one of the drug molecules in vivo resulting in lesser efficacy than expected. Vancoplus overcomes this challenge

Advancing in the Direction of Right Solutions: Treating Multidrug-Resistant Pneumonia

http://dx.doi.org/10.5772/intechopen.69979

133

Additionally, one of the biggest challenges in the management of *S. aureus* infection including all resistant versions is the management of virulence factors. Panton Valentine Leukocidin (PVL) and δ-toxin, alpha toxins are responsible for cell lysis including human erythrocytes, neutrophils, as well as various mammalian cells. β-Lactams may even induce the production of cytolysins and other virulence-related exoproteins when inadequately used for treating MRSA, which potentially worsens clinical outcomes. In the treatment of meningitis particularly it becomes added taxing issue to prevent neuronal cell damage which is caused by virulence factors generated by pathogens even if treated. Here, Vancoplus offers additional protection by neutralizing toxins secreted by pathogen and reducing sequelae drastically and

In a nut shell, a number of agencies (Infectious Diseases Society of America/American Thoracic Society, US FDA and SWAB, Asia Pacific Society for Critical Care Medicines, European Society of Intensive Care Medicines, Indian Society of Critical Care Medicines, etc.) have issued guidelines for the treatment of CAP/HAP/HCAP, CUTI/sepsis and the management of other critical ICU infections. The concept of antibiotic adjuvant entity is new and will take time to be a part of these guidelines. The author has tried to share the latest and emerging trends in MDR infection management with proven efficacy and safety in millions of patients across various developing economies. The world has now started talking about adjuvant therapy and soon these therapies will be part of standard critical infection management program. These new antibiotic additions (Elores, Potentox, and Vancoplus) to the current armamentarium to treat MDR infections including pneumonia can help us combat against antimicrobial resistance

**8.4. Adjuvant therapy to treat secondary bacterial superinfections caused by influenza** 

Viral influenza is very common in community and is often mistreated with antibiotics. Antibacterial drugs are not meant for viral infections and misuse leads to creation of resistant bacterial species. Viral-bacterial co-infections in humans are well documented. Viral infections often lead to bacterial superinfections. Bacterial superinfections accompanied by influenza and other respiratory virus infections contribute to the significant morbidity and

Bacterial infection could be concomitant with influenza viral infection as a result of an enhanced pneumonic illness or may happen soon following influenza virus has been widely cleared from the lungs, when the host seems to be more susceptible to bacterial infection [57, 58].

Morbidity and mortality have been recognized to be greater in cases of influenza-associated bacterial infection in all age groups [59]. The increase in influenza infection during winter is often associated with a rise in cases of community-acquired pneumonia. The most common

makes the product highly beneficial for immune-compromised patients [23].

more efficiently due to presence of ARB as adjuvant.

mortality particularly among elderly and young children.

**and other respiratory viruses**

effectively.

#### *8.3.1. Mechanism of action*

The vancomycin plays its bactericidal role primarily through inhibiting cell wall biosynthesis. Specifically, vancomycin forms hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the N-acetylmuramic acid- and N-acetylglucosamine-peptide subunits and thus prevents their incorporation into the peptidoglycan matrix, a major component of Gram-positive cell walls. Additionally, vancomycin is known to alter bacterial-cell-membrane permeability and RNA synthesis. No cross-resistance is known to occur between vancomycin and other antibiotics. The mechanism of action of ceftriaxone is already discussed in Elores drug section.

#### *8.3.2. Activity spectrum*

Earlier, the natural glycopeptide vancomycin was considered the drug of choice to treat MRSA infections. However, the concerns regarding the efficacy of vancomycin against MRSA including poor bactericidal activity and high recurrence rates are increasing [53]. Stevens and Moise Broder have reported in two studies, published in CID 2004 and 2006, respectively, that MRSA treatment failure rate is associated with higher vancomycin minimum inhibitory concentration (MIC). Higher vancomycin MIC is associated with higher mortality in HAP/ VAP due to MRSA. We have started witnessing vancomycin resistance, either in the intermediate range or in the full-resistance range, even in India. Among high-risk MRSA bacteremia patients, Sakoulas et al. [54] documented treatment failure rates of 44% when vancomycin MICs were <0.5 μg/ml and of 90% when vancomycin MICs were 1–2 μg/ml (*p* = 0.01) [54]. Although many other drugs including tigecycline, linezolid, and daptomycin have also been approved and represent alternate antibiotic therapy to vancomycin, no study has reported the superiority in terms of efficacy and safety of these drugs over vancomycin [55]. These clinical challenges necessitate finding alternative effective empirical solutions for the management of MRSA infections and/or mixed infections. It will be prudent to start empirically with an antibiotic which shows MIC in the susceptibility range and works effectively at lower MIC also and that is what Vancoplus offers due to double insult caused by both ceftriaxone and vancomycin. Besides this, Vancoplus effectively helps in preventing and breaking biofilm which is a very frequent problem in intubated nosocomial pneumonia patients [23].

European Antimicrobial Resistance Surveillance Network (EARS-Net) data show that the occurrence of methicillin-resistant *S. aureus* was stabilizing in several European countries; still the percentage of MRSA among all *S. aureus* isolates remained above 25% in seven of the 29 EU/EEA reporting countries. The risk factor in ICU patients increases with an increased length of stay and patients with catheter or other devices. In such cases, Vancoplus is a highly reliable product because it takes care of mixed Gram-negative and Gram-positive infections effectively. Although both these drugs have known incompatibility when given individually and needs infusion line flushing or advised to be given contralaterally, the presence of adjuvant not only potentiates the activity of duo but also makes them compatible [56]. It has been observed that when two non-compatible drugs are administered due to medical urgency with due precautions, still there exists certain degree of degradation of one of the drug molecules in vivo resulting in lesser efficacy than expected. Vancoplus overcomes this challenge effectively.

Vancoplus is a novel AAE of ceftriaxone and vancomycin along with l-arginine as adjuvant

The vancomycin plays its bactericidal role primarily through inhibiting cell wall biosynthesis. Specifically, vancomycin forms hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the N-acetylmuramic acid- and N-acetylglucosamine-peptide subunits and thus prevents their incorporation into the peptidoglycan matrix, a major component of Gram-positive cell walls. Additionally, vancomycin is known to alter bacterial-cell-membrane permeability and RNA synthesis. No cross-resistance is known to occur between vancomycin and other antibiotics. The mechanism of action of ceftriaxone is already discussed in Elores

Earlier, the natural glycopeptide vancomycin was considered the drug of choice to treat MRSA infections. However, the concerns regarding the efficacy of vancomycin against MRSA including poor bactericidal activity and high recurrence rates are increasing [53]. Stevens and Moise Broder have reported in two studies, published in CID 2004 and 2006, respectively, that MRSA treatment failure rate is associated with higher vancomycin minimum inhibitory concentration (MIC). Higher vancomycin MIC is associated with higher mortality in HAP/ VAP due to MRSA. We have started witnessing vancomycin resistance, either in the intermediate range or in the full-resistance range, even in India. Among high-risk MRSA bacteremia patients, Sakoulas et al. [54] documented treatment failure rates of 44% when vancomycin MICs were <0.5 μg/ml and of 90% when vancomycin MICs were 1–2 μg/ml (*p* = 0.01) [54]. Although many other drugs including tigecycline, linezolid, and daptomycin have also been approved and represent alternate antibiotic therapy to vancomycin, no study has reported the superiority in terms of efficacy and safety of these drugs over vancomycin [55]. These clinical challenges necessitate finding alternative effective empirical solutions for the management of MRSA infections and/or mixed infections. It will be prudent to start empirically with an antibiotic which shows MIC in the susceptibility range and works effectively at lower MIC also and that is what Vancoplus offers due to double insult caused by both ceftriaxone and vancomycin. Besides this, Vancoplus effectively helps in preventing and breaking biofilm which is

a very frequent problem in intubated nosocomial pneumonia patients [23].

European Antimicrobial Resistance Surveillance Network (EARS-Net) data show that the occurrence of methicillin-resistant *S. aureus* was stabilizing in several European countries; still the percentage of MRSA among all *S. aureus* isolates remained above 25% in seven of the 29 EU/EEA reporting countries. The risk factor in ICU patients increases with an increased length of stay and patients with catheter or other devices. In such cases, Vancoplus is a highly reliable product because it takes care of mixed Gram-negative and Gram-positive infections effectively. Although both these drugs have known incompatibility when given individually and needs infusion line flushing or advised to be given contralaterally, the presence of adjuvant not only potentiates the activity of duo but also makes them compatible [56]. It has

caters to all types of mixed infection especially MRSA, VRSA, VISA, and hGISA [43].

*8.3.1. Mechanism of action*

132 Contemporary Topics of Pneumonia

drug section.

*8.3.2. Activity spectrum*

Additionally, one of the biggest challenges in the management of *S. aureus* infection including all resistant versions is the management of virulence factors. Panton Valentine Leukocidin (PVL) and δ-toxin, alpha toxins are responsible for cell lysis including human erythrocytes, neutrophils, as well as various mammalian cells. β-Lactams may even induce the production of cytolysins and other virulence-related exoproteins when inadequately used for treating MRSA, which potentially worsens clinical outcomes. In the treatment of meningitis particularly it becomes added taxing issue to prevent neuronal cell damage which is caused by virulence factors generated by pathogens even if treated. Here, Vancoplus offers additional protection by neutralizing toxins secreted by pathogen and reducing sequelae drastically and makes the product highly beneficial for immune-compromised patients [23].

In a nut shell, a number of agencies (Infectious Diseases Society of America/American Thoracic Society, US FDA and SWAB, Asia Pacific Society for Critical Care Medicines, European Society of Intensive Care Medicines, Indian Society of Critical Care Medicines, etc.) have issued guidelines for the treatment of CAP/HAP/HCAP, CUTI/sepsis and the management of other critical ICU infections. The concept of antibiotic adjuvant entity is new and will take time to be a part of these guidelines. The author has tried to share the latest and emerging trends in MDR infection management with proven efficacy and safety in millions of patients across various developing economies. The world has now started talking about adjuvant therapy and soon these therapies will be part of standard critical infection management program. These new antibiotic additions (Elores, Potentox, and Vancoplus) to the current armamentarium to treat MDR infections including pneumonia can help us combat against antimicrobial resistance more efficiently due to presence of ARB as adjuvant.
