Published online: 2020-05-09

In the Quest of Drugs for clavulanate, and ampicillin-sulbactam; • and ; Bad Bugs: Are Newer • Aminoglycosides (i.e., gentamicin, tobramycin, and Fluoroquinolones Any amikacin);

Editor • Tigecycline; and Better? • Polymyxins (e.g., polymyxin B and colistin). to

The other group proposes that the terms, “pan drug Sir, resistance,” “extensive drug resistance,” and “multi drug The consumption of antimicrobials and the resistance” should designate, respectively, resistance of a development of bacterial resistance go hand in

Letters pathogen to all, resistance to all, but 1 or 2, and resistance hand. This is evident from the fact that soon to ≥ 3 classes of antimicrobial agents, among those that after the discovery of the first antimicrobial are available at the time of use of the definition and in compound, penicillin, reports of bacteria most parts of the world and that are regarded as potentially [1] developing resistance to it started appearing. effective against the respective pathogen.[4] Fluoroquinolones are definitely the most widely used and misused antimicrobial agents in most In this context, we evaluated the efficacy of two newer of the developing and developed nations. Since entrants in the Indian market; one third generation the serendipitous discovery of the first member fluoroquinolone, i.e., pazufloxacin (other members of of the quinolone class of drugs (, the group being levofloxacin, , , which truly is a naphthyridine derivative) as and ), and the second, a fourth generation a by-product during synthesis of antimalarial fluoroquinolone, i.e., (other members of the [2] compound, chloroquine, in 1962, a whole group being , , , and spectrum of newer quinolone compounds have ),[2] for both of which there is paucity of data been discovered which are in clinical use now- regarding their antimicrobial susceptibility profile in the a-days; some of those having been claimed to Indian scenario, but have been claimed to be effective in be effective against multi drug resistant (MDR) case of MDR - GNB and methicillin resistant Staphylococcus organisms. The definition of various classes aureus (MRSA) infections with respect to higher antimicrobial of drug resistance also varies among scientific agents like carbapenem (meropenem) and combination of community. One group proposes the carrying out beta lactam/beta lactamase inhibitor (BL-BLI, piperacillin/ surveillance of organisms on the basis of degree tazobactam). The motive of selection of these antimicrobials of MDR, and define pan drug resistance (PDR) was to evaluate whether these two higher generation and extreme drug resistance (XDR) in gram- fluoroquinolones conferred any significant additional benefit [3] negative bacilli (GNB) in the following manner. over the conventional second generation fluoroquinolones and establish any justification (if any) for their inclusion as PDR gram-negative bacilli are not susceptible a part of empirical treatment regimen in clinical conditions to all of the following : where MDR isolates are anticipated, as their inclusion would • Antipseudomonal cephalosporins significantly raise the treatment costs vis-a-vis conventional (e.g., ceftazidime and cefepime); second generation fluoroquinolones. Three MDR gram- • Antipseudomonal carbapenems negative pathogens, namely Klebsiella pneumoniae, Escherichia (e.g., imipenem and meropenem); coli, and Pseudomonas aeruginosa, in which MDR is common, • Piperacillin/tazobactam; and were included in the study. • Ciprofloxacin and levofloxacin. The susceptibility to various antimicrobial agents was XDR gram-negative bacilli are not susceptible to carried out using the Kirby Bauer disk diffusion technique all of the following antibiotics: employing commercially available antimicrobial disks • Antipseudomonal cephalosporins (HI-MEDIA Laboratories Pvt. Ltd., Mumbai, India) (e.g., ceftazidime and cefepime); following standard protocols. A total of 110 XDR - GNB • Antipseudomonal carbapenems isolates (i.e., resistant to ciprofloxacin, amikacin, cetazidime, (e.g., imipenem and meropenem); and cefepime) were included in the study. Their susceptibility • Piperacillin/tazobactam, ticarcillin- to , , pazufloxacin, prulifloxacin,

130 Journal of Laboratory Physicians / Jul-Dec 2011 / Vol-3 / Issue-2 Letters to Editor

Access this article online Table 1: Antibiogram of multi drug resistant- Quick Response Code: gram-negative bacilli Website: www.jlponline.org Isolate Antimicrobial agents (Percentage susceptibility) Ofl- Gatifl- Pazufl- Prulifl- Mero- Piperacillin/ oxacin oxacin oxacin oxacin penem tazobactam DOI: 10.4103/0974-2727.86851 Klebsiella 01 13 01 00 15 25 pneumoniae (n = 40) Escherichia 00 15 01 00 15 43 coli (n = 40) Pseudomonas 00 00 00 00 13 27 aeruginosa (n = 30) Reactive Thrombocytosis in H1N1 Infection meropenem, and piperacillin/tazobactam was determined. The observations recorded are given as under in Table 1. Sir, In case of Klebsiella pneumoniae, out of 40 isolates of the study, Platelets are acute-phase reactants and their increased 18 (45%) turned out to be PDR. In case of Escherichia coli, production secondary to systemic infections, inflammatory out of 40 isolates of the study, 18 (45%) turned out to be conditions, bleeding, and tumors is termed as reactive PDR. In case of Pseudomonas aeruginosa, out of 30 isolates of thrombocytosis.[1] We present a case series of three patients the study, 18 (60%) turned out to be PDR. with H1N1 infection in which thrombocytosis was detected as an incidental laboratory abnormality and discuss the The data in the table from our study makes it amply clear that the two newer fluoroquinolones, i.e., pazufloxacin and clinical implication and possible mechanism for the high prulifloxacin did not confer any significant additional benefit platelet count. over the conventional second generation fluoroquinolones, Three young patients with no co-morbidities presented with

i.e., ciprofloxacin, ofloxacin, and gatifloxacin. However, flu-like illness of three days duration followed by sudden additional studies on a higher sample size of the isolates onset of shortness of breath. H1N1 infection was confirmed across India will be required to formulate institution based by real-time reverse-transcriptase–polymerase-chain-reaction guidelines to incorporate representative fluoroquinolone compound in the empirical treatment regimen, which is (TaqMan A/H1N1) assay. Intensive care and invasive both rational and cost effective. It may be pointed out that mechanical ventilation was needed for management of acute a still more recent fluoroquinolone to enter Indian market respiratory distress syndrome (ARDS). During their stay is balofloxacin, which also needs to be evaluated. in intensive care unit (ICU), reactive thrombocytosis (RT), defined as platelet count above 450 × 103/mm3 was detected Antariksh Deep, Uma Chaudhary, as an incidental laboratory abnormality. The thrombocytosis Rama Sikka was benign, and so no treatment was initiated for high platelet counts [Figure1]. Onset, peak, and termination of RT were Department of Microbiology, Pt. B.D. Sharma, seen on 10-14-26; 3-9-15; and 8-12-16 day of ICU admission PGIMS, Rohtak, Haryana, India in the three patients, respectively. The maximum platelet counts were 9.15, 9.8 and 7.85 × 105cells/mm3, respectively, Address for correspondence: Dr. Antariksh Deep, in the three patients. This coincided with the resolution E-mail: [email protected] of the systemic inflammatory response (evaluated using systemic inflammatory response syndrome [SIRS] criteria) REFERENCES and the clinical recovery. Erythrocyte sedimentation rate

1. Finland M. Emergence of -resistant bacteria. N Engl J Med (ESR), a non-specific measure ofinflammation was between 1955;253:1019-28. 20-40 mm/hr during the period of RT, but normalized with 2. Andriole VT. The Quinolones: Past, Present, and Future. Clin Infect Dis clinical recovery. C-reactive protein (CRP) levels, however, 2005;41(Suppl 2):S113-9. 3. Paterson DL, Doi Y. A Step closer to extreme drug resistance in Gram could not be done. negative bacilli. Clin Infect Dis 2007;45:1179-81. 4. Falagas ME, Karageorgopoulos DE. Pandrg resistance (PDR), Extensive Secondary thrombocytosis is due to the overproduction drug resistance (XDR), and Multi drug resistance (MDR) among Gram negative bacilli: Need for international harmony in terminology. Clin of proinflammatory cytokines such as interleukin (IL)-1, Infect Dis 2008;46:1121-2. IL-6, and IL-11.[1] A "cytokine storm" is a potentially fatal

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