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Not to be confused with. Tetralogy of FallotOther namesFallot’s syndrome, Fallot’s tetrad, Steno-Fallot tetralogyDiagram of a healthy heart and one with tetralogy of Fallot,SymptomsEpisodes of, difficulty breathing,Usual onsetFrom birthCausesUnknown, 40, during pregnancyBased on symptoms,TreatmentFrequency1 in 2,000 babiesTetralogy of Fallot ( TOF) is a.

Symptoms at birth may vary from none to severe. Later, there are typically episodes of known as cyanosis. When affected babies cry or have a, they may develop a 'tet spell' where they turn very blue, have difficulty breathing, become limp, and occasionally. Other symptoms may include a, and easy tiring upon.The cause is typically not known. Risk factors include a mother who uses, has, is over the age of 40, or gets during.

It may also be associated with. Classically there are four defects:., narrowing of the exit from the right ventricle. a, a hole between the two., thickening of the right ventricular muscle. an, which allows blood from both ventricles to enter theTOF is typically treated by in the first year of life. Timing of surgery depends on the baby's symptoms and size. The procedure involves increasing the size of the and and repairing the ventricular septal defect.

In babies who are too small, a temporary surgery may be done with plans for a second surgery when the baby is bigger. Most people who are affected live to be adults. Long-term problems may include an and.TOF occurs in about 1 in 2,000 newborns. Males and females are affected equally. It is the most common complex congenital heart defect accounting for about 10 percent of cases. It was initially described in 1671. A further description was published in 1888 by the French physician, after whom it is named.

The first total surgical repair was carried out in 1954. With nail beds in an adult with tetralogy of FallotTetralogy of Fallot results in low of blood. This is due to a mixing of oxygenated and deoxygenated blood in the left ventricle via the (VSD) and preferential flow of the mixed blood from both ventricles through the aorta because of the obstruction to flow through the pulmonary valve.

The latter is known as a.Infants with TOF -a cyanotic heart disease- have low blood oxygen saturation. Blood oxygenation varies greatly from one patient to another depending on the severity of the anatomic defects. Typical ranges vary from 60% to around 90%. Depending on the degree of obstruction, symptoms vary from no cyanosis or mild cyanosis to profound cyanosis at birth.

If the baby is not cyanotic then it is sometimes referred to as a 'pink tet'. Other symptoms include a which may range from almost imperceptible to very loud, difficulty in feeding, failure to gain weight, retarded growth and physical development, labored breathing (dyspnea) on exertion, clubbing of the fingers and toes,. The baby may turn blue with breast feeding or crying. Tet spells Infants and children with unrepaired tetralogy of Fallot may develop 'tet spells'. These are acute hypoxia spells, characterized by shortness of breath, cyanosis, agitation, and loss of consciousness.

This may be initiated by any event -such as anxiety, pain, dehydration, or fever- leading to decreased oxygen saturation or that causes decreased systemic vascular resistance, which in turn leads to increased shunting through the ventricular septal defect.Clinically, tet spells are characterized by a sudden, marked increase in cyanosis followed by.Older children will often instinctively during a tet spell. This increases and allows for a temporary reversal of the. It increases pressure on the left side of the heart, decreasing the right to left shunt thus decreasing the amount of deoxygenated blood entering the systemic circulation. Cause Its cause is thought to be due to environmental or genetic factors or a combination. It is associated with chromosome 22 deletions and.Specific genetic associations include:, and.studies show that it is a result of anterior malalignment of the, resulting in the clinical combination of a VSD, pulmonary stenosis, and an overriding aorta. Right ventricular hypertrophy develops progressively from resistance to blood flow through the right ventricular outflow tract. Pathophysiology.

Video explanationThe main anatomic defect in TOF is the anterior deviation of the pulmonary outflow septum. This defect results in narrowing of the right ventricular outflow tract (RVOT), override of the aorta, and a ventricular septal defect (VSD). Four malformations ' denotes four parts, here implying the syndrome's four anatomic defects. This is not to be confused with the similarly named, a field of medicine concerned with abnormal development and congenital malformations (including tetralogy of Fallot). Below are the four malformations that present together in tetralogy of Fallot.

Normal heart ConditionDescriptionA narrowing of the right ventricular outflow tract. It can occur at the (valvular stenosis) or just below the (infundibular stenosis). Infundibular pulmonic stenosis is mostly caused by overgrowth of the heart muscle wall (hypertrophy of the septoparietal trabeculae), however the events leading to the formation of the overriding aorta are also believed to be a cause. The pulmonic stenosis is the major cause of the malformations, with the other associated malformations acting as compensatory mechanisms to the pulmonic stenosis. The degree of stenosis varies between individuals with TOF, and is the primary determinant of symptoms and severity. This malformation is infrequently described as sub-pulmonary stenosis or subpulmonary obstruction.An with biventricular connection, that is, it is situated above the ventricular septal defect and connected to both the right and the left ventricle. The degree to which the aorta is attached to the right ventricle is referred to as its degree of 'override.'

The aortic root can be displaced toward the front (anteriorly) or directly above the septal defect, but it is always abnormally located to the right of the root of the pulmonary artery. The degree of override is extremely variable, with 5-95% of the valve being connected to the right ventricle.(VSD)A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum (the outlet septum), and in the majority of cases is single and large. In some cases thickening of the septum (septal hypertrophy) can narrow the margins of the defect.The is more muscular than normal, causing a characteristic boot-shaped appearance as seen by chest X-ray.

Due to the misarrangement of the external ventricular septum, the right ventricular wall increases in size to deal with the increased obstruction to the right outflow tract. This feature is now generally agreed to be a secondary anomaly, as the level of hypertrophy tends to increase with age. Fallot's tetralogy specimen, from the UCT Pathology Learning CentreThere is anatomic variation between the hearts of individuals with tetralogy of Fallot.

Primarily, the degree of right ventricular outflow tract obstruction varies between patients and generally determines clinical symptoms and disease progression.Presumably, this arises from an unequal growth of the (aka pulmonary outflow septum). The aorta is too large, thus 'overriding,' and this 'steals' from the pulmonary artery, which is therefore stenosed. This then prevents ventricular wall closure, therefore VSD, and this increases the pressures on the right side, and so the R ventricle becomes bigger to handle the work.

Additional anomalies In addition, tetralogy of Fallot may present with other anatomical anomalies, including:. stenosis of the, in 40%. a, in 60%., in 25%. anomalies, in 10%. a patent or, in which case the syndrome is sometimes called a pentalogy of Fallot. an.

partially or totallyTetralogy of Fallot with ( pseudotruncus arteriosus) is a severe variant in which there is complete obstruction (atresia) of the right ventricular outflow tract, causing an absence of the pulmonary trunk during embryonic development. In these individuals, blood shunts completely from the right ventricle to the left where it is pumped only through the aorta. The lungs are perfused via extensive collaterals from the systemic arteries, and sometimes also via the ductus arteriosus. Diagnosis. A CXR (Chest X-Ray) of a child with tetralogy of FallotCongenital heart defects are now diagnosed with, which is quick, involves no radiation, is very specific, and can be done prenatally.establishes the presence of TOF by demonstrating a VSD, RVH, and aortic override. Many patients are diagnosed prenatally. Color Doppler (type of echocardiography) measures the degree of pulmonary stenosis.

Additionally, close monitoring of the ductus arteriosus is done in the neonatal period to ensure that there is adequate blood flow through the pulmonary valve.In certain cases, coronary artery anatomy cannot be clearly viewed using echocardiogram. In this case, cardiac catheterization can be done.Form a genetics perspective, it is important to screen for DiGeorge in all babies with TOF.Before more sophisticated techniques became available, chest x-ray was the definitive method of diagnosis. The abnormal ' (boot-like) appearance of a heart with tetralogy of Fallot is classically visible via chest x-ray, although most infants with tetralogy may not show this finding.

The boot like shape is due to the right ventricular hypertrophy present in TOF. Lung fields are often dark (absence of interstitial lung markings) due to decreased pulmonary blood flow.Electrocardiography shows right ventricular hypertrophy (RVH), along with right axis deviation. RVH is noted on EKG as tall R-waves in lead V1 and deep S-waves in lead V5-V6. Treatment Tet spells Tet spells may be treated with such as, but acute episodes require rapid intervention with or intranasal to reduce ventilatory drive, a vasopressor such as, or to increase systemic vascular resistance, and IV fluids for volume expansion.Oxygen (100%) may be effective in treating spells because it is a potent pulmonary vasodilator and systemic vasoconstrictor. This allows more blood flow to the lungs by decreasing shunting of deoxygenated blood from the right to left ventricle through the VSD. There are also simple procedures such as and the knee chest position which increase systemic vascular resistance and decrease right-to-left shunting of deoxygenated blood into the systemic circulation.If the spells are refractory to the above treatments, people are usually intubated and sedated.

The treatment of last resort for tet spells is (ECMO) along with consideration of Blalock Taussig shunt (BT shunt). Total surgical repair Total surgical repair of TOF is a curative surgery. Different techniques can be used in performing TOF repair. However, a transatrial, transpulmonary artery approach is used for most cases. The repair consists of two main steps: closure of the VSD with a patch and reconstruction of the right ventricular outflow tract.This open-heart surgery is designed to relieve the right ventricular outflow tract stenosis by careful of muscle and to repair the VSD. Additional reparative or reconstructive surgery may be done on patients as required by their particular cardiac anatomy.Timing of surgery in asymptomatic patients is usually between the ages of 2 months to one year.

However, in symptomatic patients showing worsening blood oxygen levels, severe tet-spells (cyanotic spells), or dependence on prostaglandins from early neonatal period (to keep the ductus arteriosus open) need to be planned fairly urgently.Potential surgical repair complications include residual ventricular septal defect, residual outflow tract obstruction, complete atrioventricular block, arrhythmias, aneurysm of right ventricular outflow patch, and pulmonary valve insufficiency. Long term complications most commonly include pulmonary valve regurgitation, and arrhythmias.Total repair of tetralogy of Fallot initially carried a high mortality risk, but this risk has gone down steadily over the years. Surgery is now often carried out in infants one year of age or younger with less than 5% perioperative mortality. Post surgery, most patients enjoy an active life free of symptoms. Currently, long term survival is close to 90%.

Today the adult TOF population continues to grow and is one of the most common congenital heart defect seen in adult outpatient clinics. Palliative surgery Initially surgery involved forming a side to end between the and the -i.e a systemic to pulmonary arterial shunt. This redirected a large portion of the partially oxygenated blood leaving the heart for the body into the lungs, increasing flow through the pulmonary circuit, and relieving symptoms.

The first surgery was performed on 15-month-old on November 29, 1944 with dramatic results.The Potts shunt and the Waterston-Cooley shunt are other shunt procedures which were developed for the same purpose. These are no longer used.Currently, palliative surgery is not normally performed on infants with TOF except for extreme cases. For example, in symptomatic infants, a two-stage repair (initial systemic to arterial shunt placement followed by total surgical repair) may be done. Potential complications include inadequate pulmonary blood flow, pulmonary artery distortion, inadequate growth of the pulmonary arteries, and acquired pulmonary atresia. Prognosis Untreated, tetralogy of Fallot rapidly results in progressive right ventricular hypertrophy due to the increased resistance caused by narrowing of the pulmonary trunk. This progresses to heart failure which begins in the right ventricle and often leads to left heart failure and dilated cardiomyopathy. Mortality rate depends on the severity of the tetralogy of Fallot.

If left untreated, TOF carries a 35% mortality rate in the first year of life, and a 50% mortality rate in the first three years of life. Patients with untreated TOF rarely progress to adulthood.Patients who have undergone total surgical repair of tetralogy of Fallot have improved hemodynamics and often have good to excellent cardiac function after the operation with some to no exercise intolerance (New York Heart Association Class I-II).

Long-term outcome is usually excellent for most patients, however residual post surgical defects -such as pulmonary regurgitation, pulmonary artery stenosis, residual VSD, right ventricular dysfunction, right ventricular outflow tract obstruction, and sudden death- may affect life expectancy and increase the need for reoperation.Within 30 years after correction, 50% of patients will require reoperation. The most common cause of reoperation is a leaky pulmonary valve. This is usually corrected with a procedure called.

Epidemiology Tetralogy of Fallot occurs approximately 400 times per million live births. It accounts for 7 to 10% of all congenital heart abnormalities, making it the most common cyanotic heart defect. Males and females are affected equally. Genetically it is most commonly associated with Down's syndrome and DiGeorge syndrome.

History Tetralogy of Fallot was initially described in 1671. A further description was published in 1888 by the French physician, after whom it is named. In 1924, Maude Abbott coined the term 'tetralogy of Fallot'.The first surgical repair was carried out in 1944 at Johns Hopkins. The procedure was conducted by surgeon and cardiologist, with also providing substantial contributions and listed as an assistant. This first surgery was depicted in the film. It was actually Helen Taussig who convinced Alfred Blalock that the shunt was going to work. 15-month-old was the first person to receive a.

Furthermore, the Blalock-Thomas-Taussig procedure, initially the only surgical treatment available for tetralogy of Fallot, was palliative but not curative. The first total repair of tetralogy of Fallot was done by a team led by at the in 1954 on an 11-year-old boy. Total repair on infants has had success from 1981, with research indicating that it has a comparatively low mortality rate. Today the adult TOF population continues to grow and is one of the most common congenital heart defect seen in adult outpatient clinics. Notable cases., American professional snowboarder and skateboarder., Australian cricketer., New Zealand author and publisher., Volkswagen's 'Little Darth Vader' from the 2011 Super Bowl commercial. Billy Kimmel, the son of talk show host; Billy's diagnosis led Kimmel to discuss access to health care on his showSee also.References.

Enterobacter cloacae is among the most important pathogens responsible for nosocomial infections and outbreaks. In this study, 77 Enterobacter isolates were collected: 27 isolates from Algerian hospitals (in Constantine, Annaba, and Skikda) and 50 isolates from Marseille, France. All strains were identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS).

Antibiotic susceptibility testing was performed by the disk diffusion method. PCR was used to detect extended-spectrum-beta-lactamase (ESBL)-encoding, fluoroquinolone resistance-encoding, and aminoglycoside-modifying enzyme (AME) genes. Epidemiological typing was performed using MALDI-TOF MS with data mining approaches, along with multilocus sequence typing (MLST). Sixty-eight isolates (27 from Algeria, 41 from Marseille) were identified by MALDI-TOF MS as E. Resistance to antibiotics in the Algerian isolates was significantly higher than that in the strains from Marseille, especially for beta-lactams and aminoglycosides. Eighteen of the 27 Algerian isolates and 11 of the 41 Marseille isolates possessed at least one ESBL-encoding gene: bla CTX-M and/or bla TEM.

AME genes were detected in 20 of the 27 Algerian isolates and 8 of the 41 Marseille isolates ant(2″)- Ia, aac(6′)- Ib-cr, aadA1, aadA2, and armA. Conjugation experiments showed that armA was carried on a transferable plasmid. MALDI-TOF typing showed three separate clusters according to the geographical distribution and species level. An MLST-based phylogenetic tree showed a clade of 14 E. Cloacae isolates from a urology unit clustering together in the MALDI-TOF dendrogram, suggesting the occurrence of an outbreak in this unit.

In conclusion, the ability of MALDI-TOF to biotype strains was confirmed, and surveillance measures should be implemented, especially for Algerian patients hospitalized in France. INTRODUCTIONEnterobacter cloacae is an opportunistic pathogen that can cause several type of infections in the lower respiratory tract, surgical sites, urinary tract , and central nervous system ; moreover, it is frequently associated with nosocomial infections in outbreaks, and thus there is a need for rapid detection and typing of such strains.

Although multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) are good approaches to identify the spread of a given clone in an outbreak, these techniques remain time-consuming with a substantial cost. Recently, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has been introduced in clinical microbiology as a routine tool for rapid identification of bacteria at the species level , but it also could be used as a simple tool for typing in nosocomial outbreaks of infections with bacteria such as Acinetobacter baumannii.

Antibiotic resistance in E. Cloacae is being increasingly reported, with the acquisition of genes encoding extended-spectrum beta-lactamases (ESBLs) and aminoglycoside-modifying enzymes (AMEs) being the most critical factor in antibiotic resistance. Therefore, epidemiological plans of antibiotic resistance surveillance have been deployed for several years to measure the evolution of the antibiotic resistance phenomenon and to detect outbreaks (, ).

Some recent investigations reported in Algeria have revealed an increase in ESBL-producing E. Cloacae, with bla CTX-M1, bla CTX-M3, bla CTX-M15, bla VEB-1, bla SHV-12, and bla TEM (, ) being the most frequent genes detected. However, the epidemiology and molecular support of resistance to aminoglycosides due to AMEs in E. Cloacae have never been studied in Algeria, even though they have been reported recently in Acinetobacter baumannii and Klebsiella pneumoniae (, ). Indeed, we recently reported an outbreak in a pediatric Algerian hospital of K. Pneumoniae infections with strains harboring both genes encoding ESBLs and the armA 16S rRNA methyltransferase gene. Here, we investigate and compare the prevalences and molecular support of antibiotic resistance to aminoglycosides, beta-lactams, and fluoroquinolones in a series of E.

Cloacae clinical isolates from Constantine, Annaba, and Skikda in Algeria and from Marseille in France. Moreover, we used MALDI-TOF MS and data mining approaches, along with MLST, to study relationships between these isolates to assess whether MALDI-TOF can be used for real-time detection of multidrug-resistant (MDR) E.

Cloacae during an outbreak. Antibacterial susceptibility testing.Antibiotic susceptibility testing was performed by the disk diffusion method on Mueller-Hinton agar (Becton, Dickinson and Company, France), as recommended by the Antibiogram Committee of the French Society for Microbiology (CA-SFM 2013 Ver. Phenotypic identification of ESBLs was determined in a systematic manner using a double-disk synergy test by placing disks of ceftazidime, cefotaxime, cefepime, and aztreonam equidistant from a disk with a combination of amoxicillin and clavulanic acid. The test was considered positive when a “champagne cork” aspect was observed. Molecular characterization of antibiotic resistance-encoding genes.DNA extraction from all isolates was performed using EZ1 DNA extraction kits (Qiagen, Courtaboeuf, France) with the EZ1 Advanced XL bio-robot according to the manufacturer's instructions. ESBL-encoding genes ( bla CTX-M, bla TEM, bla SHV, bla VEB, bla GES, bla PER) , quinolone antibiotic resistance determinants ( qnrA, qnrB) , and AME-encoding genes armA, aad, rmt, aph, ant2, aac(6)-Ib in both the Algerian and Marseille isolates were detected by PCR, as previously described.

Positive PCR products were purified and sequenced using a BigDye Terminator v3.1 cycle sequencing kit (Applied Biosystems, Foster City, CA, USA). The analysis was performed using an ABI 3130 automated sequencer (Applied Biosystems, Foster City, CA, USA). The obtained sequences were analyzed using CodonCode Aligner software and then aligned with those from the National Center for Biotechnology Information and ARG-ANNOT sequence databases using the BLAST program. Conjugation and resistance transfer.The transfer of antibiotic resistance by conjugation was performed using five E. Cloacae isolates as donors (three from Algeria and two from Marseille) and E.

Coli J53, which is resistant to sodium azide, as the recipient strain. Both the recipient and donor strains were cultivated in tryptic soy broth (Becton, Dickinson and Company, France) at 37°C for 24 h, mixed at a 1:10 donor-to-recipient ratio, and incubated overnight at 37°C with shaking.

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The transconjugants were selected by plating 10 μl of the mixture on Luria-Bertani agar (Becton, Dickinson and Company, France) containing 200 mg/liter of sodium azide and 20 mg/liter of ceftazidime. Antibacterial susceptibility tests and PCR were performed on the transconjugants to confirm the transfer of antibiotic resistance genes. Source of samples and units.Among our 77 clinical isolates of Enterobacter spp., 27 were collected from Algerian patients with a mean age of 35 years (range, 8 to 62 years), and 50 isolates originated from patients in Marseille, France, with a mean age of 40.7 years (range, 1 month to 89 years). The most common specimen was urine for both the Algerian and Marseille isolates, at 60% and 26%, respectively, followed by pus for the Algerian isolates (22%) and sputum for the Marseille isolates (24%). MALDI-TOF MS identification and clustering.All Enterobacter species isolates were correctly identified at the species level by MALDI-TOF MS (Bruker Daltonics), with a score value of 1.9, as follows: 68 E.

Cloacae complex isolates (63 E. Cloacae, 3 E. Asburiae, 1 E. Ludwigii, and 1 E. Cancerogenus isolate) and 9 E.

Aerogenes isolates. According to an arbitrary cutoff set up at a distance level of 500, the MSP dendrogram revealed 3 clusters: cluster C1 contained only the 9 E. Aerogenes isolates from Marseille, cluster C2 contained 29 E. Cloacae isolates from Marseille, and cluster C3 contained 12 E. Cloacae complex isolates from Marseille and 27 E. Cloacae complex isolates from Algeria. Thus, cluster C2 was significantly associated with the Marseille isolates ( P.

Antibacterial susceptibility testing.Disk diffusion susceptibility testing revealed that all E. Cloacae strains were susceptible to imipenem and colistin. However, the Algerian isolates had significantly higher percentages of resistance to third-generation cephalosporins than the Marseille isolates (18/27 versus 11/41, P = 0.002). This was also the case for resistance to fluoroquinolones in the Algerian strains compared to those from Marseille (10/27 versus 5/41, P = 0.03), as well as for aminoglycoside resistance (20/27 in the Algerian isolates versus 8/41 in the Marseille isolates) ( P. Molecular characterization of antibiotic resistance.Among the 18 Algerian E. Cloacae isolates that showed an ESBL phenotype, 13 (72.2%) isolates had both CTX-M15 and TEM-1, whereas 3 (16.6%) and 2 (11.1%) isolates carried only CTX-M15 or TEM-1, respectively.

However, 11 isolates from Marseille were found to be ESBL-producing E. Cloacae, with 6 (54.5%) isolates harboring CTX-M15 and 1 (9%) harboring TEM-1; 4 (36.4%) carried both CTX-M15 and TEM-1 ( P = 0.002).

The fluoroquinolone resistance gene detection results were as follows: in the Algerian isolates, we found qnrB42 in 8 strains along with aac(6′ )-Ib-cr (80%), qnrB1 in one strain (10%), and aac(6′ )-Ib-cr alone in one strain (10%); in the Marseille isolates, we detected qnrB42 in 2 strains (40%), qnrB1 in one strain (20%), and qnrA1 in 2 strains (40%) ( P = 0.03). The aminoglycoside resistance was due to the following AME-encoding genes: aac(6′ )-Ib-cr in 9 Algerian strains (45%), in association with ant(2″ )-Ia and aadA2 in one Algerian strain and with aadA2 and armA in 3 Algerian strains.

Eleven (55%) Algerian strains were found to harbor aadA2. In the Marseille strains, aac(6′ )-Ib-cr was found in one strain along with aadA1 (12.5%), and aadA1 was present separately in 3 strains (37.5%) and ant(2″ )-Ia in 4 strains (50%) ( P. RegionYr(s) of studyβ-LactamsQuinolonesAminoglycosidesReferenceNo. Of isolatesGene(s) detectedNo. Of isolatesGene(s) detectedNo. Of isolatesGenes detectedBejaia2004–20051/44bla CTX-M3ND20072/2bla CTX-M152/2qnrBNDAlgiers2003–200725/141bla CTX-M15, bla CTX-M3, bla VEB-1, bla SHV-125/141qnrB1, qnrB4, qnrS1NDTlemcen20082/NMbla CTX-M15NDAnnaba200913/65bla CTX-M1NDTlemcen2008–20104/4bla CTX-M15NDAnnaba200930/63bla CTX-M, bla TEMNDEastern Algeria: Constantine, Annaba, Skikda201318/27bla CTX-M15, bla TEM-110/27qnrB1, qnrB4220/27aadA2, ant2, armA, aac(6′)-Ib-crPresent study.

MLST.The obtained sequences of the seven loci of the 68 E. Cloacae isolates were concatenated and then used to build a phylogenetic tree. Cloacae NCTC 9394 was used as a reference strain. The MLST-based phylogenetic tree revealed the presence of 37 STs containing 21 new STs described for the first time in this study. However, within these 37 STs, we identified a small cluster of 7 STs belonging to clonal complex 1 (ST6, ST90, ST177, ST221, ST224, ST226, ST228).

This cluster contains isolates from the same ward (urology unit) that harbored the armA gene on a plasmid, suggesting an outbreak. DISCUSSIONEnterobacter cloacae strains are frequently responsible for nosocomial infections and outbreaks, including urinary tract infections, pneumonia, and bloodstream infections.

The increase in resistance and the emergence of MDR strains in both Algerian and French hospitals necessitate the implementation of epidemiological surveillance. This study showed a rate of ESBL-producing E.

Cloacae isolates from eastern Algeria in 2013 of 67%, which is higher than the ESBL production reported in previous epidemiological studies in Algeria: 2.3% in 2004 , 17.7% in 2007 , and 47% in 2009. The value obtained is also higher than the rate of ESBL production by E. Cloacae isolated in Marseille (30%). This can be explained by the overuse of antibiotics in Algerian hospitals. The observed resistance is due to the presence of worldwide-spread CTX-M15 and TEM-1 genes in these Algerian and Marseille isolates, which have been described in previous studies. Our study reports the first identification of qnrB42 in E.

Cloacae isolates from both Algeria and France, although it was previously detected in one K. Pneumoniae isolate from Algeria and in France. QnrB1 was previously described in Algerian E. Cloacae strains but not in France; we also report qnrA1 in Marseille isolates, as was detected in a previous study.

Fluoroquinolone resistance was also associated with the presence of aac(6′ )-Ib-cr, which also confers resistance to aminoglycosides, in both the Algerian and Marseille strains. This study presents the first report of the armA 16S rRNA methyltransferase gene in E. Cloacae in Algeria and Africa in three strains; it has been reported in an Algerian K. Pneumoniae isolate and in two E. Cloacae strains in Belgium.

None of our Marseille strains carried the armA gene; however, it has been detected in one E. Cloacae strain of 12 clinical isolates of Enterobacteriaceae in France. The presence of aadA1, aadA2, and ant2 in E. Cloacae is exclusively described in this study. AadA2 and aadA1 were recently described in K.

Pneumoniae in Algeria, and another variant ( aadA6) was detected in Pseudomonas aeruginosa strains in Korea.MALDI-TOF MS has been successfully used for the identification of E. The MSP dendrogram clustering of isolates showed significant clusters based on discrimination between Enterobacter species ( E. Aerogenes and E. Cloacae complex). The isolates were also separated according to their geographical origin (Marseille or Algeria), which can be important for rapidly detecting the sources of pathological isolates and is supported by Berrazeg et al.

in their study of 535 strains of K. According to the MLST analysis, among the 37 STs found in our study, 4 STs were common in the Algerian and Marseille isolates, with the remaining strains being heterogeneous, with 21 new STs. Moreover, we identified a specific clade that includes 7 STs (ST6, ST90, ST177, ST221, ST224, ST226, ST228) belonging to the same clonal complex (CC1) , with 14 Algerian isolates emerging in a uro-nephrology unit. Thus, the isolates were clustered together in the MALDI-TOF MS dendrogram as well as in the MLST-based phylogenetic tree, confirming the suitability of MALDI-TOF MS for biotyping and outbreak detection (, ). Indeed, this clade suggests the occurrence of an outbreak in this uro-nephrology unit within a period of 4 months, between November 2012 and February 2013, with an unknown common source of transmission.

The transmission could be due to hand carriage by paramedical personnel (, ) or a contaminated cytoscope, which is typically used to place double J catheters, especially in urology clinics.This outbreak was associated with the presence of the armA 16S rRNA methyltransferase gene in three of the E. Cloacae Algerian isolates, and this gene was carried on a conjugative plasmid along with aadA2, bla CTX-M15, and bla TEM-1. This situation can promote the rapid dissemination of armA in various members of the Enterobacteriaceae family ( K. Pneumoniae in Algeria , Escherichia coli, A. Baumannii, and Serratia in China ).The armA 16S rRNA methyltransferase gene underlies strong resistance to all aminoglycosides, which usually have a broad antimicrobial spectrum and efficiency, and the cooccurrence of this gene with ESBL-encoding genes presents a real clinical concern. Indeed, this may be a major therapeutic threat in the future , as aminoglycoside and beta-lactam combinations, which are widely used by clinicians to treat severe bacterial infections based on their synergistic effects, are no longer a solution. Furthermore, with the rapid increase in ESBL-producing strains, imipenem has been massively used and in turn has induced the emergence of carbapenem resistance genes, especially in Gram-negative bacteria, as reported in many epidemiological studies from around the world, including Algeria, where oxacillinases and NDM-1 were detected in A.

Baumannii and VIM-2 in P. Aeruginosa.Hence, to reduce the frequency of MDR bacteria, clinicians and health professionals, particularly in Algeria, should pay attention to the uncontrolled use of antibiotics and should refer to antibiotic susceptibility testing methods for the choice of an effective treatment.Our study demonstrates in a very significant way the high level of strains resistant to the most common antibiotic families in Algeria compared to Marseille, France.

Surveillance measures should be systematically implemented when treating an Algerian patient hospitalized in France.