Pandrug-resistant Infections

Introduction

The research paper by Yadav et al. ¹ reporting that pan-resistant infections (PDR) by Enterobacteriaceae and Proteus are susceptible to the combination of ceftriaxone + sulbactam + EDTA, makes interesting reading.

In this context, I wish to share the following observations for the benefit of your readers.

First, undoubtedly further in vitro studies with special reference to minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in different centers are warranted to confirm the findings of the aforesaid study. Moreover, in vivo studies involving actual patients in healthcare centers too are needed. This is a fact that the in vitro sensitivity observations do not necessarily get reflected in actual clinical effectiveness and efficacy. Mercifully, in the recent past, integration of the pharmacodynamic and pharmacokinetic indices has considerably enhanced the correlation between in vitro susceptibility testing and in vivo clinical effectiveness. As a result, now more realistic breakpoints can be allowed.

Second, pandrug resistance (PDR) to gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus, Enterobacteriaceae, and Acinetobacter is on an increase globally. Nonetheless, this is not true that PDR is restricted to only gram-negative bacteria. Staphylococcus aureus, a gram-positive bacteria, may too develop PDR.

Third, PDR infections are a huge challenge in pharma­cotherapeutics. Individuals having health issues or compromised immune systems are often at the highest risk for getting such an infection. The two most common types of bacteria that can become resistant to antibiotics are S. aureus and Enterococcus.

Fourth, there is considerable confusion in the literature about what really constitutes PDR, especially in relation to extensive drug resistance (XDR). ² As clarified in Table 1, XDR is resistance to all classes of antibiotics except 1 or 2. On the other hand, PDR is resistant to all classes of antibiotics. In other words, there is a non-susceptibility of the bacteria to all antimicrobial agents in all antimicrobial categories. The term, PDR, has also been employed for pathogens that are specifically resistant to seven antimicrobial agents (cefepime, ceftazidime, imipenem, meropenem, piperacillin-tazobactam, ciprofloxacin, and levofloxacin).

While efforts at determining a combination of potential antimicrobials with beta-lactamase inhibitors are in progress, research endeavors need to be boosted for the development and introduction into clinical practice of new antimicrobial agents.

Finally, prevention of PDR infections, a public health problem, ³ needs a special emphasis. Judicious use of antibiotics and strict infection control measures are mandatory to reduce the prevalence of drug resistance. The proactive propagation of antimicrobial stewardship program ⁴ in letter and spirit in healthcare facilities may prove a “game changer” in containing the malady.

REFERENCES

1. Yadav S, Mangalesh S, Makkar A, et al. In vitro evaluation of a novel derivative combination antimicrobial ceftriaxone + sulbactam + EDTA against panresistant gram-negative bacteria at a 1,000-bedded tertiary care teaching hospital in northern India. J Med Acad 2020;3(1):11–13. DOI: 10.47008/ajm.2020.3.1.3.

2. Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria. Clin Microb Infect 2011;8(3):268–281.

3. Gupte N. Antimicrobial resistance: time to fight it out. Pediat Infect Dis 2012;1(4):15–17.

4. Gupte N. Antimicrobial stewardship: the crying need of the time. EC Pharama Toxicol (London) 2020;8(8):1–2.