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\title{Prevalence of Beta-Lactamase Producers in ICUs of a Tertiary Care Teaching Hospital of North India}
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             \author[1]{Dr. Poonam  Sharma}

             \author[2]{Dr. Sarbjeet  Sharma}

             \author[3]{Dr. Jasvir  kaur}

             \affil[1]{  GuruRamdas Institute of Medical Sciences And Research, Vallah, Amritsar, Punjab}

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\date{\small \em Received: 9 December 2014 Accepted: 2 January 2015 Published: 15 January 2015}

\maketitle


\begin{abstract}
        


The aim of this study was to identify prevalence rates, sites and types of infection, the most common bacteria, and their antimicrobial resistance patterns, especially betalactamase producers present in Intensive care units (ICUs) of a tertiary care hospital.Methods: Clinical samples obtained over a period of 12months from January 2014 to December 2014 from six ICUs of a tertiary care hospital were analyzed. Identification of micro organisms to species level and their antimicrobial susceptibility testing was performed as per CLSI guidelines. For control, 500 samples each from the environment & staff of ICU were collected & processed in the same way.

\end{abstract}


\keywords{intensive care units, prevalence, betalactamase producers, cross-infection.}

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\let\tabcellsep& 	 	 		 
\section[{I. Introduction}]{I. Introduction}\par
ntensive care units (ICUs) are of great value in the control and treatment of the severe illnesses that affect the human body. In spite of their invaluable and well-established role, ICUs lead to some degree of morbidity to patients, and nosocomial infection is clearly related to that.\par
Exposure to life-saving invasive procedures, serious underlying disease of patients and increased patient contact with healthcare personnel put patients admitted to the ICU at higher risk of acquiring nosocomial infections. ICU staff and the equipment used for patient care during the hospitalisation are the primary sources of cross-transmission of nosocomial pathogens.\par
Nosocomial infections increase patient morbidity, length of hospital stay, hospital costs, and may also increase mortality rates. When serious infections are suspected, treatment must be commenced immediately to increase the likelihood of a satisfactory outcome for the patient. Empirical knowledge, to select appropriate antibiotics, must be used so that the most likely infecting organisms are treated.\par
The prevalence of ICU-acquired infections varies between 4.4\% and 88.9\% being significantly higher in developing countries than in developed countries \hyperref[b0]{(1)}. Furthermore, device-associated infection rates in developing countries, especially ventilatorassociated pneumonia (VAP) followed by central venous catheter-related bloodstream infections (CRBSIs), occur at a higher frequency than in European countries and USA \hyperref[b1]{(2,}\hyperref[b2]{3)}.\par
The aim of this study was to identify the prevalence rates, sites and types of infection, the most prevalent microorganisms, and the antimicrobial resistance patterns especially the beta-lactamase producers present in ICUs of a tertiary care hospital. 
\section[{II. Materials and Methods}]{II. Materials and Methods}\par
The present study was conducted in 6 intensive care units of a tertiary care teaching hospital .We retrospectively analyzed consecutive culture-positive isolates and studied the antimicrobial susceptibility patterns of micro-organisms during the period from January 2014 to December 2014. The BacT/Alert (bioMerieux) was used for blood culture. Identification of micro organisms to species level and antimicrobial susceptibility testing was performed by the Vitek method. The interpretation of antimicrobial susceptibility results was done as per Clinical and Laboratory Standard Institute (CLSI) guidelines (4). For control, 500 samples each from the environment \& staff of ICU were collected \& processed in the same way. Informed consent was taken from staff before collecting samples. This study was conducted on hospitalised patients from whom samples were received in microbiology department so the article didn't need an approval from ethical committee. 
\section[{a) Statistical Analysis}]{a) Statistical Analysis}\par
Statistical analysis was conducted. The chisquare test and odds ratio was applied for the comparison of categorical variables. P values less than 0.05 were considered as statistically significant. 
\section[{III. Results}]{III. Results}\par
Total number of clinical samples collected during one year period were 1545. Out of which, 522 were culture positive as shown in Table1. The prevalence of Gram positive and Gram negative isolates in environmental \& staff samples is shown in Table \hyperref[tab_2]{3}. The prevalence of ?-lactamase producing Gram negative and Gram positive isolates in clinical, environmental \& staff samples is shown in Table \hyperref[tab_3]{4} \& 5 respectively.  ( D D D D ) C 9.\par
Beta lactamase producers were maximum in clinical samples followed by environmental and staff samples as shown in Table \hyperref[tab_5]{6}. 10. By calculating the odds ratio, isolates from clinical samples were twice more likely to be beta lactamase producers than the ones from environmental samples (odds ratio=2.98) and isolates from clinical samples were four times (odds ratio=3.94) more likely to be betalactamase producers than from staff samples. 11. By using chi-square test no significant (p=0.2) association was found between isolates from environmental and staff samples. 
\section[{V. Discussion}]{V. Discussion}\par
In this study, Gram-negative bacteria were more common than Gram-positive bacteria, which is in accordance with the other studies \hyperref[b4]{(5,}\hyperref[b5]{6,}\hyperref[b6]{7)}. Treatment becomes challenging in gram-negative organisms causing serious infections in ICUs including pneumonia, bloodstream infections, wound or surgical site infections and meningitis. These organisms also exhibit multidrug resistance, and therapeutic alternatives have declined due to stagnation in novel antimicrobial agents \hyperref[b6]{(7,}\hyperref[b7]{8)}.\par
In the present study, blood stream infections were most common, followed by urinary tract, wound and respiratory infections. However in the study by Boyles S (9) respiratory infections were more common in ICU followed by wound, blood stream and urinary tract infections. The probable reason could be that the sample size in their study was much larger (14000 patients) than ours.\par
Acinetobacter species was the most common pathogen isolated which is in accordance with the study by Datta P et al \hyperref[b5]{(6,}\hyperref[b6]{7)}. The prevalence of MRSA among clinical, environmental and staff samples was more than 50\% which shows that more stress should be laid on hand hygiene in our ICUs as improved hand hygiene can reduce acquisition of antimicrobial resistant bacteria, particularly MRSA \hyperref[b9]{(10)}.\par
There has been increase in incidence of beta lactam resistant organisms in ICUs of our hospital which is in accordance with a study conducted by Shaikh S et al \hyperref[b10]{(11)}. Among the clinical isolates, 50.8\% of Gram negative isolates and 56.4\% of Gram positive isolates were beta lactamase producers. This data confirms that in the intensive care medical environment, the most virulent in general are the most resistant and are the most frequently found organisms \hyperref[b11]{(12,}\hyperref[b12]{13)}.\par
Prevalence of beta-lactamase producers in environmental and staff samples apart from clinical samples indicates towards the possibility of cross infection by these organisms from the environment and staff to the patients. Infection control strategies such as hand hygiene, rational antibiotic use, training and performance feedback can lead to significant reduction in the cross infection rates. In addition patients colonized or infected with beta lactamase-producing organism should be placed under contact precautions to avoid hospital transmission \hyperref[b13]{(14)}.\par
Hand hygiene is the most important way of decreasing the spread of infections in ICUs especially in developing countries like ours. Initial empirical therapy with broad-spectrum antibiotics is a life-saving strategy, which improves clinical outcome and reduces selection of resistant organisms. However, it is imperative to deescalate these antibiotics according to culture and antibiotic susceptibility results. Antibiotic cycling can be used as an effective approach to control antibiotic resistance. Strict antibiotic policies in ICUs can prevent the use of long term antibiotics and shorten the duration of the antimicrobial therapy \hyperref[b14]{(15)}.\par
Conducting infection surveillance and control activities in ICUs and rational antibiotic utilisation policies are valuable measures for infection control. These measures provide current knowledge about antibiotic resistance patterns, early recognition and management of outbreaks, which is essential for infection control \hyperref[b15]{(16)}.\par
Increasing drug resistance and spreading of multidrug-resistant (MDR) pathogens in the ICU environment results in limited therapeutic options and prolonged hospitalisations.\par
Consequently, the prevalence of ICU-acquired infection, healthcare costs and mortality rates are higher in developing countries due to limited resources associated with the quality of care \hyperref[b16]{(17)}.\par
In conclusion, our study shows that multidrug resistant bacteria are on rise in our hospital. The rise in beta-lactamase producers emphasizes the importance of stringent infection control practices, rational prescribing policies and need for development of new drugs and vaccines. Also, there is a need for the continuous evaluation of the local antibiotic resistance patterns for the formulation of a rational antibiotic policy. Limiting use of antibiotics to patients with clear evidence of infection rather than colonization is essential \& discontinuation of antibiotics when their possible benefits have been obtained is also critical. Further, new drugs are required to replace the increasingly obsolete classes of antibiotics that currently exist and there is need for strict compliance with infection control practices.  
\section[{Volume XV Issue III Version I}]{Volume XV Issue III Version I}\begin{figure}[htbp]
\noindent\textbf{1} \par 
\begin{longtable}{P{0.3275609756097561\textwidth}P{0.13682926829268294\textwidth}P{0.18451219512195122\textwidth}P{0.20109756097560974\textwidth}}
S.no.\tabcellsep Samples\tabcellsep Total no.\tabcellsep Positive\\
1\tabcellsep Blood\tabcellsep 704\tabcellsep 158 (22.4\%)\\
2\tabcellsep Urine\tabcellsep 498\tabcellsep 118 (23.7\%)\\
3\tabcellsep Pus\tabcellsep 160\tabcellsep 124 (77.5\%)\\
4\tabcellsep Suction tip\tabcellsep 100\tabcellsep 83 (83\%)\\
5\tabcellsep Respiratory\tabcellsep 47\tabcellsep 33 (70.2\%)\\
6\tabcellsep Body fluids\tabcellsep 27\tabcellsep 02 (7.4\%)\\
7\tabcellsep Central lines\tabcellsep 09\tabcellsep 04 (44.4\%)\\
\tabcellsep \tabcellsep 1545\tabcellsep 522 (33.8\%)\\
\multicolumn{2}{l}{The percentage of Gram negative organisms}\tabcellsep \multicolumn{2}{l}{(101/522) \& that of Candida was 0.76\% (4/522) as}\\
\multicolumn{2}{l}{isolated from clinical samples was79.88\% (417/522), the}\tabcellsep shown in\tabcellsep \\
\multicolumn{2}{l}{percentage of gram positive organisms was 19.37\%}\tabcellsep \tabcellsep \end{longtable} \par
 
\caption{\label{tab_0}Table 1 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{22} \par 
\begin{longtable}{P{0.22067307692307694\textwidth}P{0.4822115384615384\textwidth}P{0.14711538461538462\textwidth}}
S.No.\tabcellsep ORGANISM\tabcellsep TOTAL No.\\
1\tabcellsep ACINETOBACTER\tabcellsep 151\\
2\tabcellsep E.COLI\tabcellsep 105\\
3\tabcellsep S. AUREUS\tabcellsep 93\\
4\tabcellsep ENTEROBACTER\tabcellsep 89\\
5\tabcellsep PSEUDOMONAS\tabcellsep 29\\
6\tabcellsep KLEBSIELLA\tabcellsep 21\\
7\tabcellsep CITROBACTER\tabcellsep 16\\
8\tabcellsep ENTEROCOCCUS\tabcellsep 06\\
9\tabcellsep PROTEUS\tabcellsep 06\\
10\tabcellsep CANDIDA\tabcellsep 04\\
11\tabcellsep CONS???\tabcellsep 02\\
\tabcellsep Total\tabcellsep 522\\
\multicolumn{2}{l}{???Coagulase Negative Staphylococcus}\tabcellsep \end{longtable} \par
 
\caption{\label{tab_1}Table 2 .Table 2 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{3} \par 
\begin{longtable}{P{0.2056451612903226\textwidth}P{0.26733870967741935\textwidth}P{0.19193548387096773\textwidth}P{0.18508064516129033\textwidth}}
Year 2 015\tabcellsep \tabcellsep \tabcellsep \\
Volume XV Issue III Version I\tabcellsep \tabcellsep \tabcellsep \\
D D D D ) C\tabcellsep \tabcellsep \tabcellsep \\
(\tabcellsep \tabcellsep \tabcellsep \\
S.No.\tabcellsep ISOLATES\tabcellsep Environment\tabcellsep Staff\\
1\tabcellsep Gram positive\tabcellsep 50(10\%)\tabcellsep 34 (6.8\%)\\
2\tabcellsep Gram negative\tabcellsep 78(15.6\%)\tabcellsep 208 (41.6\%)\\
3\tabcellsep Positive samples\tabcellsep 128 (25.6\%)\tabcellsep 242 (48.4\%)\\
4\tabcellsep Sterile samples\tabcellsep 372 (74.4\%)\tabcellsep 258 (51.6\%)\\
\tabcellsep Total samples\tabcellsep 500\tabcellsep 500\end{longtable} \par
 
\caption{\label{tab_2}Table 3 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{4} \par 
\begin{longtable}{P{0.019725738396624472\textwidth}P{0.15063291139240506\textwidth}P{0.15063291139240506\textwidth}P{0.1882911392405063\textwidth}P{0.034071729957805906\textwidth}P{0.13090717299578059\textwidth}P{0.039451476793248945\textwidth}P{0.13628691983122362\textwidth}}
SNo.\tabcellsep ORGANISMS\tabcellsep \multicolumn{6}{l}{CLINICAL ISOLATES ENVIRONMENTAL ISOLATES ISOLATES FROM STAFF}\\
\tabcellsep \tabcellsep TOTAL\tabcellsep BETA\tabcellsep TOTAL\tabcellsep BETA\tabcellsep TOTAL\tabcellsep BETA\\
\tabcellsep \tabcellsep \tabcellsep LACTAMASES\tabcellsep \tabcellsep LACTAMASES\tabcellsep \tabcellsep LACTAMASES\\
\tabcellsep \tabcellsep \tabcellsep PRODUCING\tabcellsep \tabcellsep PRODUCING\tabcellsep \tabcellsep PRODUCING\\
1\tabcellsep ACINETOBACTER\tabcellsep 151\tabcellsep 88 (58.3\%)\tabcellsep 12\tabcellsep 0\tabcellsep 20\tabcellsep 2 (10\%)\\
2\tabcellsep E.COLI\tabcellsep 105\tabcellsep 56 (53.3\%)\tabcellsep 22\tabcellsep 08 (36.3\%)\tabcellsep 52\tabcellsep 10 (19.2\%)\\
3\tabcellsep ENTEROBACTER\tabcellsep 89\tabcellsep 31 (34.8\%)\tabcellsep 14\tabcellsep 02\tabcellsep 10\tabcellsep 0\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep (14.3\%)\tabcellsep \tabcellsep \\
4\tabcellsep PSEUDOMONAS\tabcellsep 29\tabcellsep 15\tabcellsep 10\tabcellsep 02\tabcellsep 46\tabcellsep 10(21.7\%)\\
\tabcellsep \tabcellsep \tabcellsep (51.7\%)\tabcellsep \tabcellsep (20\%)\tabcellsep \tabcellsep \\
5\tabcellsep KLEBSIELLA\tabcellsep 21\tabcellsep 13\tabcellsep 20\tabcellsep 10\tabcellsep 70\tabcellsep 22 (31.4\%)\\
\tabcellsep \tabcellsep \tabcellsep (61.9\%)\tabcellsep \tabcellsep (50\%)\tabcellsep \tabcellsep \\
6\tabcellsep CITROBACTER\tabcellsep 16\tabcellsep 09\tabcellsep 0\tabcellsep 0\tabcellsep 06\tabcellsep 0\\
\tabcellsep \tabcellsep \tabcellsep (56.3\%)\tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
7\tabcellsep PROTEUS\tabcellsep 06\tabcellsep 0 (0\%)\tabcellsep 0\tabcellsep 0\tabcellsep 04\tabcellsep 0\\
\tabcellsep Total\tabcellsep 417\tabcellsep 212 (50.8\%)\tabcellsep 78\tabcellsep 22\tabcellsep 208\tabcellsep 44\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep (28.2\%)\tabcellsep \tabcellsep (21.2\%)\end{longtable} \par
 
\caption{\label{tab_3}Table 4 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{5} \par 
\begin{longtable}{P{0.35182783018867925\textwidth}P{0.022051886792452832\textwidth}P{0.03758844339622641\textwidth}P{0.022051886792452832\textwidth}P{0.0070165094339622635\textwidth}P{0.3643573113207547\textwidth}P{0.01653891509433962\textwidth}P{0.028567216981132074\textwidth}}
\multicolumn{2}{l}{S.No. ORGANISMS}\tabcellsep \multicolumn{4}{l}{CLINICAL ISOLATES ENVIRONMENTAL ISOLATES}\tabcellsep \multicolumn{2}{l}{ISOLATES FROM STAFF}\\
\tabcellsep \tabcellsep TOTAL\tabcellsep BETA\tabcellsep TOTAL\tabcellsep BETA\tabcellsep TOTAL\tabcellsep BETA\\
\tabcellsep \tabcellsep \multicolumn{2}{l}{LACTAMASES}\tabcellsep \tabcellsep LACTAMASES\tabcellsep \tabcellsep LACTAMASES\\
\tabcellsep \tabcellsep \multicolumn{2}{l}{PRODUCING}\tabcellsep \tabcellsep PRODUCING\tabcellsep \tabcellsep PRODUCING\\
1\tabcellsep MSSA\tabcellsep 36\tabcellsep 17(47\%)\tabcellsep 18\tabcellsep 08 (44.4\%)\tabcellsep 14\tabcellsep 04 (28.6\%)\\
2\tabcellsep MRSA\tabcellsep 57\tabcellsep 40 (70\%)\tabcellsep 06\tabcellsep 04 (66.7\%)\tabcellsep 08\tabcellsep 04 (50\%)\\
3\tabcellsep CONS\tabcellsep 02\tabcellsep 0\tabcellsep 26\tabcellsep 0\tabcellsep 12\tabcellsep 00\\
4\tabcellsep ENTEROCOCCI\tabcellsep 06\tabcellsep 01 (16.7\%)\tabcellsep 0\tabcellsep 0\tabcellsep 0\tabcellsep 0\\
\tabcellsep Total\tabcellsep 101\tabcellsep 57 (56.4\%)\tabcellsep 50\tabcellsep 12 (24\%)\tabcellsep 34\tabcellsep 08 (23.5\%)\\
\tabcellsep \multicolumn{2}{l}{IV. Observations}\tabcellsep \tabcellsep \tabcellsep \multicolumn{3}{l}{5. Among the clinical isolates, 50.8 \%( 212/417) of}\\
\multicolumn{5}{l}{1. Maximum number of infections in ICU were Blood stream infections followed by Urinary tract, wound and respiratory tract infections. 2. Among the clinical isolates, the most prevalent bacterial agent was Acinetobacter 28.9\% (151/522), followed by organisms of family Enterobacteriaceae and Staphylococcus aureus, 3. Concerning resistance patterns for S. aureus, 61.3\% were resistant to methicillin and 100\% had sensitivity to vancomycin. 4. Isolates obtained from staff samples were more than the ones obtained from clinical samples. More than 50\% S.aureus obtained from staff \& environmental samples were Methicillin resistant (MRSA) however all were sensitive to Vancomycin.}\tabcellsep \multicolumn{3}{l}{Gram negative isolates and 56.4 \%( 57/101) of Gram positive isolates were beta latamase producers. 6. The most frequently used antimicrobials in ICUs were cephalosporins, imipenem, levofloxacin, piperacillin-tazobactum and metronidazole. Actually, empirical treatment schemes are based on knowledge of local microbiota 7. E.coli \& Klebsiella sp were the most common isolates recovered from environment \& staff of ICU. Acinetobacter followed by E. coli were the more prevalent isolates from clinical samples 8. Prevalence of Gram negative organisms was more than gram positive in all the 3 groups as shown in Table 6.}\end{longtable} \par
 
\caption{\label{tab_4}Table 5 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{6} \par 
\begin{longtable}{P{0.1913907284768212\textwidth}P{0.1576158940397351\textwidth}P{0.13509933774834437\textwidth}P{0.1576158940397351\textwidth}P{0.20827814569536424\textwidth}}
ISOLATES\tabcellsep TOTAL PERCENTAGE\tabcellsep GRAM POSITIVE\%\tabcellsep GRAM NEGATIVE \%\tabcellsep BETA\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep LACTAMASES\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep PRODUCERS\\
CLINICAL\tabcellsep 33.8\tabcellsep 19.4\tabcellsep 79.8\tabcellsep 51.9\\
ENVIRONMENTAL\tabcellsep 25.6\tabcellsep 10\tabcellsep 15.6\tabcellsep 26.56\\
STAFF\tabcellsep 48.4\tabcellsep 6.8\tabcellsep 41.6\tabcellsep 21.48\end{longtable} \par
 
\caption{\label{tab_5}Table 6 :}\end{figure}
 			\footnote{© 2015 Global Journals Inc. (US)} 		 		\backmatter  			 
\subsection[{Conflict of Interest Statement}]{Conflict of Interest Statement}\par
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