Increasing resistance to ciprofloxacin among isolates of Neisseria gonorrhoea in Dublin

Neisseria gonorrhoeae cases are increasing in Ireland. Ciprofloxacin is often used as first line treatment for this infection in STI clinics. A retrospective study to analyze resistance in two Dublin clinics was undertaken. Cases were defined as patients from whom an isolate of N. gonorrhoea was recovered. All cases from two clinics between January 1997 and June 2003 were included. Antimicrobial resistance data was correlated with sex and sexuality. One thousand one hundred and eighty laboratory-confirmed cases were identified. Eighty seven percent were male. Sixty nine percent were MSM. Twenty seven percent of isolates demonstrated reduced susceptibility to penicillin and 6% to ciprofloxacin. Isolates with reduced susceptibility to ciprofloxacin increased year on year from 3.8% in 1997 to 15% in 2003. Prevalence of isolates of N. gonorrhoea with reduced susceptibility to ciprofloxacin has exceeded 10% in these clinics since 2002. In concordance with international guidelines, ceftriaxone became the treatment of choice for gonorrhoea in July 2003.     

Risk factors of ciprofloxacin resistance in urinary Escherichia coli isolates

BACKGROUND AND PURPOSE: Increasing rates of fluoroquinolone resistance among Escherichia coli have been reported in Taiwan and worldwide. We aimed to identify the risk factors of ciprofloxacin resistance in urinary E. coli isolates. METHODS: Patients with positive urine culture result for E. coli and resistance to ciprofloxacin between September 1, 1999 and December 31, 1999 were prospectively identified as cases, and compared with ciprofloxacin-susceptible E. coli isolates (controls). The case:control ratio was 1:2. Data were collected with standardized case record forms. RESULTS: Sixty one cases and 122 controls were compared. Multivariate analysis indicated that urinary tract catheterization (odds ratio [OR] = 2.631, 95% confidence interval [CI] = 1.058-6.544; p=0.037) and prior exposure to quinolones (OR = 13.072, 95% CI = 3.367-50.75; p<0.001) were independent risk factors for ciprofloxacin resistance in urinary E. coli isolates. Compared with ciprofloxacin-susceptible E. coli isolates, ciprofloxacin-resistant E. coli isolates from urine specimens had a significantly higher rate of resistance to all other tested antimicrobial agents, except amikacin and imipenem. CONCLUSION: In patients with urinary tract infection, urinary catheterization and prior quinolone exposure are associated with a high risk of ciprofloxacin-resistant E. coli which may cause treatment failure.     

Consanguinity profile in the Gaza Strip of Palestine: Large-scale community-based study

Consanguineous marriages which have been practiced throughout history continue to be practiced within different ethnic, religious and social groups to varying degrees with highest prevalences in North Africa, Middle East and central and south Asia. In the Gaza Strip of Palestine, little is known about the consanguinity profile, so the present large-scale study aims to explore the consanguinity profile of two generations using data from the β-thalassemia premarital screening program. Sociodemographic data analysis included 156,635 (141,200 males and 15,435 females) persons and their parents, representing 141,200 couples who were referred to the Thalassemia and Hemophilia Center for premarital testing. In addition, the consanguinity characteristics of parents of 217 transfusion-dependent β-thalassemic non-sibling patients were analyzed. Results revealed a significant decrease in the overall prevalence of consanguineous (first- and second-cousin) marriages between the previous (fathers') generation (45.2%) and the current (groom/bride) generation (39.9%). Among the five governorates of the Gaza Strip, records of Gaza Governorate revealed the lowest occurrence (36.9% current generation and 42.1% previous generation) of consanguineous marriages, as compared to all others. Consanguineous marriages are significantly higher in semi-urban areas (41.6%) than in urban areas (39.1%) in the current generation (previous generation, 46.4% vs 44.7%, respectively). Compound consanguinity (two generation) and a single level of consanguinity were seen in 20.7% and 43.7%, respectively, of the cases. The average age of those with first-cousin marriages is significantly lower (22.4 ± 4.4 years) than those with second-cousin marriages (24.3 ± 6.1 years) and the non-consanguineous (26.5 ± 8.2 years). The rate of consanguineous marriages among never married people (42.2%) is significantly much higher than the rate of people with multiple marriages (18.1%). About 74.7% of the non-sibling thalassemic patients of the Gaza Strip are associated with consanguineous parents, of them 54.4% first-cousins and 20.3% second-cousins.In conclusion, although there is a decline in the consanguinity profile in the present compared to previous generation, consanguineous marriages are still a common practice in the Gaza Strip, which rationalizes the necessity for more awareness and counseling efforts about the potential health-related risks of consanguinity on individual lives and the population overall.     

National G6PD neonatal screening program in Gaza Strip of Palestine: rationale,challenges and recommendations

Congenital genetic disorders affecting neonates or young children can have serious clinical consequences if undiagnosed and left untreated. Early detection and an accurate diagnosis are, therefore, of major importance for preventing negative patient outcomes. Even though the occurrence of each specific metabolic disorder may be rare, their collective impact of preventable complications may be of considerable importance to the public health. Our previous studies showed that glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is a problem of public health importance that has been shown to be a predominant cause of acute hemolytic anemia requiring hospitalization in Palestinian young children in Gaza Strip. Intriguingly, the majority of these children had one of the three variants, Mediterranean^c.563T, African G6PD A?^{c.202A/c.376G} and heretofore unrecognized as a common G6PD‐deficient variant G6PD Cairo^c.404C. The high prevalence of G6PD deficiency, as well as dietary factors in the region that precipitate anemia, argues for a need to protect the Palestinian children from a treatable and manageable genetic and metabolic disorder. This work reviews and discusses rationales and challenges of G6PD screening program in Gaza Strip. We advocate adopting a national neonatal G6PD screening program in Gaza Strip to identify children at risk and promote wellness and health for Palestine.     

Antibacterial activity of norfloxacin against bacterial isolates from the urinary tract

Two hundred fourteen isolates from clinical specimens were tested in vitro to determine their susceptibility pattern against norfloxacin. Of the 151 strains of gram-negative bacteria tested, 149 (98.7%) were susceptible. Sixty-three (100%) of the gram-positive bacteria tested were also susceptible to norfloxacin. Norfloxacin showed excellent activity against all bacteria isolated from urine.     

Clonality among ampicillin-resistant Enterococcus faecium isolates in Sweden and relationship with ciprofloxacin resistance

Objective  To investigate clonal relationships in a nationwide sample of human Enterococcus faecium isolates.
Methods  Biochemical fingerprinting (PhP (PhenePlate) typing) was used to compare 180 fecal ampicillin-resistant E. faecium (ARE) isolates with 169 matched fecal ampicillin-susceptible E. faecium (ASE) isolates from patients in 23 hospitals, collected in 1998, and to study 39 fecal ARE isolates from non-hospitalized individuals collected in 1998, and five ARE and 29 ASE isolates from the early 1990s. Representative ARE and ASE isolates were subjected to pulsed-field gel electrophoresis (PFGE) analysis of genomic DNA and sequencing of the regions encoding the fluoroquinolone targets of the enzymes GyrA and ParC.
Results  Both PhP and PFGE results showed a higher homogeneity among ARE than among ASE isolates ( P  < 0.001). One PhP type (FMSE1) comprised 73% of the hospital ARE isolates (53% of ARE isolates from non-hospitalized individuals, and four of five ARE isolates from the early 1990s), but only 1% of the ASE isolates. PFGE of the hospital E. faecium isolates revealed that 23 of the 25 ARE isolates and one of the 22 ASE isolates were of one dominating type. High-level resistance to ciprofloxacin (MIC > 16 mg/L) was present in 91% of ARE isolates, whereas only low-level resistance (MIC 4–16 mg/L; 35% of isolates) was found among ASE isolates. One mutation in parC (codon 80) and one of two mutations in gyrA (codons 83 or 87) were detected in all ARE isolates tested with high-level ciprofloxacin resistance, but were lacking in ARE and ASE isolates with low-level ciprofloxacin resistance.
Conclusion  Most ARE isolates in Sweden were clonally related. High-level ciprofloxacin resistance was found in ARE isolates of PhP type FMSE1 as well as in other PhP types, but never in ASE isolates.     

Synergism of trimethoprim and ciprofloxacin in vitro against clinical bacterial isolates

For the first time, the effects of combinations of trimethoprim and a fluoroquinolone (ciprofloxacin) against gram-positive and gram-negative bacterial isolates were evaluated in vitro. Synergism was found in 31 % (fractional inhibitory concentration, FIC) and 33 % (fractional bactericidal concentration, FBC) of 121 clinical isolates of various bacterial strains, most often inEscherichia coli, staphylococci, and enterococci. Antagonism occurred in 1 % (FIC) and 3 % (FBC). The combination of trimethoprim and ciprofloxacin merits further evaluation for potential usefulness as a clinical regimen.Deceased 11 October, 1991.     

Biofilm formation among methicillin-resistant Staphylococcus aureus isolates from patients with urinary tract infection

Staphylococci have been confirmed to form biofilms on various biomaterials. The purpose of this study was to investigate biofilm formation among methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with urinary tract infection (UTI) and to assess the relationship between biofilm-forming capacities and virulence determinants/clinical background. Over a 12-year period from 1990 through 2001, a total of 109 MRSA isolates were collected from patients (one isolate per patient) with UTI at the urology ward of Okayama University Hospital. We used the in vitro microtiter plate assay to quantify biofilm formation. We then investigated the presence of several virulence determinants by polymerase chain reaction assay and found eight determinants (tst, sec, hla, hlb, fnbA, clfA, icaA, and agrII) to be predominant among these isolates. Enhanced biofilm formation was confirmed in hla-, hlb-, and fnbA-positive MRSA isolates, both individually and in combination. Upon review of the associated medical records, we concluded that the biofilm-forming capacities of MRSA isolates from catheter-related cases were significantly greater than those from catheter-unrelated cases. The percentage of hla-, hlb-, and fnbA-positive isolates was higher among MRSA isolates from catheter-related cases than those from catheter-unrelated cases. Our studies suggest that MRSA colonization and infection of the urinary tract may be promoted by hla, hlb, and fnbA gene products.     

Susceptibility of European respiratory tract isolates to trovafloxacin, ciprofloxacin, clarithromycin, azithromycin and ampicillin

As part of the Artemis project, 11 500 isolates (3000 from patients with respiratory tract infections) were collected throughout six European countries between 1994 and 1996. Twenty-seven hospitals or laboratories participated in this first phase of the study. The activities of three classes of antimicrobial agents (fluor-oquinolones,-lactam agents, macrolides) are presented for the six most frequently isolated pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Klebsiella pneumoniae). Overall, trovafloxacin and ciprofloxacin activities were similar forHaemophilus influenzae, Moraxella catarrhalis andKlebsiella pneumoniae isolates. Of theStreptococcus pneumoniae isolates, 6% were resistant to penicillin. Trovafloxacin had the highest activity against theStreptococcus pneumoniae isolates, with a minimum inhibitory concentration of 0.25 mg/l for 90% of isolates (MIC₉₀); all strains tested were susceptible to trovafloxacin. The MIC₉₀ of ciprofloxacin forStreptococcus pneumoniae was 3 mg/l, and overall 52% of the strains were susceptible; 9% were resistant. Azithromycin and clarithromycin exhibited similar activity against all collected pathogens, exceptHaemophilus influenzae. All strains ofHaemophilus influenzae were susceptible to azithromycin compared with 79% for clarithromycin, with respective MIC₉₀s of 2 and 16 mg/l. The data presented demonstrate differences in the susceptibility patterns of six major respiratory tract pathogens in Europe.     

Fluorescent amplified fragment length polymorphism probabilistic database for identification of bacterial isolates from urinary tract infections

The ability of the fluorescent amplified fragment length polymorphism (FAFLP) technique to identify bacterial isolates from urinary tract infections (UTIs) was investigated. FAFLP was carried out using the single primer combination MseI plus CT and EcoRI plus 0, and information-rich FAFLP profiles were generated from all 69 UTI isolates studied, which comprised both gram-negative and gram-positive bacteria encompassing eight genera. The genetic relatedness of these 69 bacteria was determined by cluster analysis, and this revealed eight main groups corresponding to the eight bacterial genera. Finer discrimination on the same dendrogram showed species and subspecies differentiations, thus demonstrating the potential of FAFLP for describing a wide diversity range within microbial populations. The interpretation of FAFLP profiles is often complicated because it relies upon the investigator interpreting dendrograms; this process may be subjective if the tree is complicated, particularly if it includes polytomies (unresolved nodes). Therefore, we have developed a method based on Bayes' theorem for the identification of bacteria against an FAFLP probabilistic identification matrix. Thus, FAFLP is suitable for the objective identification of causal agents of UTI, and the procedure offers great potential in the clinical laboratory.     

Single-dose ciprofloxacin in the treatment of uncomplicated urinary tract infection in women

In a randomised, double-blind trial two single-dose regimens of ciprofloxacin were evaluated for treatment of acute urinary tract infection (UTI) in women. Fifty-three women received 250mg and 46 750mg of ciprofloxacin. Seven days after treatment the eradication rate was 81.1% and 82.6% in the low and high dose groups respectively; the clinical cure rate at 28 days was 64.1% and 73.9% respectively. In women with recurrent UTI a significantly better response was found with the high dose regimen (92% versus 68%; p<0.001). It is concluded that a single 250mg dose of ciprofloxacin is effective for treatment in most women with acute UTI, but in women with recurrent infection a 750mg dose is preferable.     

Multidrug resistance in pediatric urinary tract infections

Urinary tract infections (UTIs) represent a common infection in the pediatric population. Escherichia coli is the most common uropathogen in children, and antimicrobial resistance in this species complicates the treatment of pediatric UTIs. Despite the impact of resistance on empiric antibiotic choice, there is little data on multidrug resistance in pediatric patients. In this paper, we describe characteristics of multidrug-resistant E. coli in pediatric patients using a large national database of uropathogens antimicrobial sensitivities. Antimicrobial susceptibility patterns to commonly prescribed antibiotics were performed on uropathogens isolated from children presenting to participating hospitals between 1999 and 2001. Data were analyzed separately for four pediatric age groups. Single and multidrug resistance to ampicillin, amoxicillin-clavulanate, cefazolin, ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole (TMP-SMX) were performed on all specimens. There were a total of 11,341 E. coli urine cultures from 343 infants (0-4 weeks), 1,801 toddlers (5 weeks-24 months), 6,742 preteens (2-12 years), and 2,455 teens (13-17 years). E. coli resistance to ampicillin peaked in toddlers (52.8%) but was high in preteens (52.1%), infants (50.4%), and teens (40.6%). Resistance to two or more antibiotics varied across age groups, with toddlers (27%) leading preteens (23.1%), infants (21%), and teens (15.9%). Resistance to three or more antibiotics was low in all age groups (range 3.1-5.2%). The most common co-resistance in all age groups was ampicillin/TMP-SMZ. In conclusion, less than half of all pediatric UTIs are susceptible to all commonly used antibiotics. In some age groups, there is a significant percentage of co-resistance between the two most commonly used antibiotics (ampicillin and TMP-SMZ).     

Occurrence of extended spectrum beta-lactamases among isolates of Enterobacteriaceae from urinary tract infections in southern Italy

The present investigation was undertaken to assess the prevalence of extended-spectrum beta-lactamases (ESbetaLs) among urinary tract infection (UTI) isolates. During 4 months in 2004, a total of 650 Enterobacteriaceae strains from UTIs was collected by five clinical microbiology laboratories located in southern Italy and the beta-lactamase production was investigated. A total of 50 of the 650 isolates were double-disk positive and suspected of producing an ESbetaL; Escherichia coli (36.0%) and Klebsiella pneumoniae (32.0%) were the most common species among all ESbetaL producers. Characterization of ESbetaL determinants was carried out by the colony blot hybridization method, and polymerase chain reaction (PCR) and DNA sequencing in order to identify the presence of bla (TEM), bla (SHV), bla (PER), and bla (CTX-M) determinants. The ESbetaL variants found in this study were the following: TEM-15, TEM-24, TEM-52, TEM-134, SHV-12, CTX-M-1, CTX-M-3, CTX-M-15, and PER-1. As expected, the majority of the isolates were found to be susceptible to imipenem (94%), cefepime (54%) and piperacillin-tazobactam (54%). The results of this survey show the prevalence of ESbetaL enzymes among enterobacterial pathogens causing UTIs in southern Italy.     

Evolution of fluoroquinolone resistance among Escherichia coli urinary tract isolates from a French university hospital: application of the dynamic regression model

Escherichia coli urinary tract isolates were collected in 1997-2003 from Nimes University Hospital in order to investigate long-term trends in antibiotic resistance and to explore the relationship between antibiotic use and the emergence of resistance. Time-series analysis (ARIMA models) and dynamic regression models were used to investigate relationships between antibiotic use and resistance to ofloxacin and ciprofloxacin. Significant increases were seen in the frequency of ofloxacin (8.9 to 16.7%) and ciprofloxacin resistance (6.2 to 10.1%) (p < 0.001). Using multivariate dynamic regression analysis, it was found that an increased use of one defined daily dose (DDD)/1000 patient-days for ofloxacin, ciprofloxacin and norfloxacin induced average increases of 0.81%, 0.65% and 0.53% in E. coli ofloxacin resistance (p < 0.01), with average delays of 4, 4 and 6 months, respectively. An increase of 1 DDD/1000 patient-days of ciprofloxacin, ofloxacin and norfloxacin use induced increases of 0.73%, 0.82% and 0.63% in E. coli ciprofloxacin resistance (p < 0.01), with average delays of 4, 4 and 5 months, respectively. The use of nalidixic acid was not associated significantly with an increase in resistance to fluoroquinolones by multivariate analysis.     

Regulation of production of type 1 pili among urinary tract isolates of Escherichia coli.

The piliation and hemagglutination properties of 54 consecutive Escherichia coli isolates from women with recurrent urinary tract infections were studied. Mannose-sensitive hemagglutination (MSHA) of guinea pig erythrocytes, characteristic of type 1-piliated bacteria, was produced by 75% of the isolates, 32% produced mannose-insensitive hemagglutination, and 14% produced no hemagglutination reaction. The production of type 1 pili was examined in those strains that produced MSHA only. Studies with antiserum prepared against purified pili suggested that at least three subtypes of type 1 hemagglutinins were represented among the isolates. All of the type 1-piliated isolates produced MSHA after serial subculture in static broth. After growth on agar, selected type 1-piliated isolates were subdivided into two groups. Many strains apparently suppressed piliation during growth on agar (regulated variants); all colonies became MSHA negative and were composed of nonpiliated cells as shown by electron microscopy. The loss of the MSHA phenotype often occurred after a single overnight passage on agar, and any remaining hemagglutinin was gradually lost with one to three additional passages. Seven strains, however, retained a significant hemagglutination titer after multiple subcultures on agar, and they produced colonies consisting of a mixed population of piliated and nonpiliated cells. These strains were apparently able to oscillate between states of pilus expression and nonexpression during growth on agar (random phase variants). When nonpiliated cells isolated from the mixed, random variant population were plated on agar, they gave rise to hemagglutination-positive colonies that consisted of both piliated and nonpiliated cells. The distinction between random variants and regulated variants was also observed in shaking broth cultures inoculated with nonpiliated cells. The random variants produced MSHA-positive cultures composed of piliated and nonpiliated cells, whereas the regulated strains remained nonpiliated. The results indicate that type 1 pili are a predominant adhesin of uropathogenic E. coli and that during growth on agar only about one-fourth of the type 1-piliated isolates regulate pilus expression by random phase variation.     

High incidence of penicillin resistance amongst clinical isolates of Streptococcus pneumoniae in northern Palestine

One hundred and thirteen consecutive isolates of Streptococcus pneumoniae were collected in Nablus, Palestine between March and Aug. 1997 from children with acute lower respiratory tract infections. Resistance rates were: penicillin 88%, cefuroxime 85%, erythromycin 63%, tetracycline 45%, chloramphenicol 27% and ofloxacin 2%. Resistances to erythromycin and cefuroxime were significantly associated with penicillin resistance. Ofloxacin may be useful against pneumococci resistant to traditional antimicrobial agents. Factors associated with penicillin resistance included hospitalisation and previous use of beta-lactam antibiotics.