The ticking time bomb: escalating antibiotic resistance in Neisseria gonorrhoeae is a public health disaster in waiting.

J Antimicrob Chemother. 2012 May 17;

Authors: Whiley DM, Goire N, Lahra MM, Donovan B, Limnios AE, Nissen MD, Sloots TP

Abstract
From a once easily treatable infection, gonorrhoea has evolved into a challenging disease, which in future may become untreatable in certain circumstances. International spread of extensively drug-resistant gonococci would have severe public health implications. It seems clear that under the current treatment pressure from extended-spectrum cephalosporins, and owing to Neisseria gonorrhoeae's remarkable evolutionary adaptability, further rise of ceftriaxone-resistant strains around the world is inevitable. Simply increasing the doses of extended-spectrum cephalosporins will likely prove ineffective in the long run, and has been a lesson learnt for all single-agent therapies used for gonorrhoea to date. We recommend that dual therapy, especially those consisting of extended-spectrum cephalosporins and azithromycin, be adopted more widely and complemented by strengthening of antimicrobial resistance surveillance. Unless there is urgent action at international and local levels to combat the problem of N. gonorrhoeae antimicrobial resistance, we are in for gloomy times ahead in terms of gonorrhoea disease and control.

PMID: 22604449 [PubMed - as supplied by publisher]

Nosocomial transmission of community-associated methicillin-resistant Staphylococcus aureus in Danish Hospitals.

J Antimicrob Chemother. 2012 Apr 20;

Authors: Hetem DJ, Westh H, Boye K, Jarløv JO, Bonten MJ, Bootsma MC

Abstract
OBJECTIVES: The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the epidemiology of MRSA infections worldwide. In contrast to hospital-associated MRSA (HA-MRSA), CA-MRSA more frequently affects healthy individuals, both with and without recent healthcare exposure. Despite obvious epidemiological differences, it is unknown whether differences in nosocomial transmissibility exist. We have, therefore, quantified the transmissibility, expressed by the single admission reproduction number (R(A)), of CA-MRSA and HA-MRSA in hospital settings in Denmark. METHODS: MRSA index cases and secondary cases were investigated in four hospitals in the Copenhagen area. Index cases were defined as non-isolated, non-screened patients with MRSA, and secondary cases were defined as persons carrying MRSA isolates-identical to that of the corresponding index-as identified through contact screening. CA-MRSA and HA-MRSA were categorized upon genotyping [CA-MRSA: t008-ST8, PVL+; t019-ST30, PVL+; t127-ST1, PVL+; t044-ST80, PVL+; and their related spa types; and HA-MRSA: all other (where ST stands for sequence type and PVL stands for Panton-Valentine leucocidin)]. A mathematical model was applied to determine the genotype-specific transmission rate (i.e. R(A)) of CA-MRSA and HA-MRSA strains. RESULTS: During the 7 year study period there were 117 MRSA index cases with subsequent post-contact screening (of 1108 patients and healthcare workers), revealing 22 outbreaks with a total of 52 secondary patients. R(A) values were 0.07 (95% CI 0.00-0.28) and 0.65 (95% CI 0.48-0.84) for CA-MRSA and HA-MRSA, respectively. CONCLUSIONS: In four Danish hospitals the nosocomial transmission rate of CA-MRSA was 9.3 times lower than that of HA-MRSA.

PMID: 22523315 [PubMed - as supplied by publisher]

Assessment of the activity of ceftaroline against clinical isolates of penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae with elevated MICs of ceftaroline using an in vitro pharmacodynamic model.

J Antimicrob Chemother. 2012 Mar 30;

Authors: Zhanel GG, Yachison C, Nichol K, Adam H, Noreddin AM, Hoban DJ, Karlowsky JA

Abstract
OBJECTIVES: This study assessed the pharmacodynamics of ceftaroline against penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae with elevated MICs of ceftaroline using an in vitro pharmacodynamic model. METHODS: Nine isolates of S. pneumoniae, including one penicillin-susceptible isolate, one penicillin-intermediate isolate and seven penicillin-resistant isolates, were tested. The pharmacodynamic model was inoculated with a concentration of 1?×?10(6) cfu/mL and ceftaroline was dosed twice daily (at 0 and 12 h) to simulate the fC(max) (maximum free concentration in serum) and t(1/2) (half-life in serum) obtained after 600 mg intravenous doses every 12 h (fC(max), 16 mg/L; t(1/2), 2.6 h). Ceftaroline was compared with ceftriaxone dosed once daily to simulate the fC(max) and t(1/2) obtained after a 1 g dose (fC(max), 18 mg/L; t(1/2), 8.0 h). Samples were collected over 24 h to assess viable growth and possible changes in ceftaroline MICs over time. RESULTS: Ceftaroline fT(>MIC) (time of free serum concentration over the MIC) of 100% (ceftaroline MICs, ?0.5 mg/L) was bactericidal (?3 log(10) killing) against all isolates at 6 h and completely eradicated all organisms at 12 and 24 h. No bacterial regrowth occurred over the study period and no changes in ceftaroline MICs were observed. Upon ceftriaxone exposure, S. pneumoniae isolates with ceftriaxone MICs of 0.12 and 0.25 mg/L were eradicated, but isolates with ceftriaxone MICs of 1-8 mg/L resulted in initial bacterial reduction at 6 h with organism regrowth at 12 h and no reduction in organism concentration, relative to the starting inoculum, at 24 h. CONCLUSIONS: Ceftaroline fT(>MIC) of 100% (ceftaroline MICs, ?0.5 mg/L) was bactericidal (?3 log(10) killing) and eradicated all S. pneumoniae at 12 and 24 h with no regrowth.

PMID: 22467630 [PubMed - as supplied by publisher]

Antimicrobial resistance among non-fermenting Gram-negative bacteria in Saudi Arabia.

J Antimicrob Chemother. 2012 Mar 29;

Authors: Memish ZA, Shibl AM, Kambal AM, Ohaly YA, Ishaq A, Livermore DM

Abstract
OBJECTIVES: Non-fermentative Gram-negative bacilli (non-fermenters) can cause serious healthcare-associated infections and are often resistant to multiple antibiotics. We examined resistance rates among these bacteria from different regions of Saudi Arabia. METHODS: A cross-sectional study between January and December 2009 examined 8908 clinical non-fermenters from 24 hospitals across Saudi Arabia. Susceptibility testing was monitored to ensure compliance with CLSI guidelines, but the antibiotics tested were at the hospitals' discretion. RESULTS: Out of the 8908 non-fermenters, most were Pseudomonas aeruginosa (72.9%), followed by Acinetobacter baumannii (25.3%) and Stenotrophomonas maltophilia (1.8%). Resistance rates among P. aeruginosa were: polymyxin B, 2.2%; imipenem, 15.9%; ciprofloxacin, 22.0%; amikacin, 22.9%; and gentamicin, 31.2%. Resistance rates among A. baumannii were: imipenem, 5.4%; polymyxin B, 13.2%; ciprofloxacin, 64.0%; trimethoprim/sulfamethoxazole, 73.8%; amikacin, 76.9%; and gentamicin, 77.8%. Resistance rates among S. maltophilia were: polymyxin B, 6.9%; trimethoprim/sulfamethoxazole, 20.5%; and ciprofloxacin, 38.9%. There was major variation in resistance rates between geographical regions. CONCLUSIONS: Resistance rates among non-fermenters were high in Saudi Arabia and were variable among regions.

PMID: 22461312 [PubMed - as supplied by publisher]

Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae and patient outcome: a meta-analysis.

J Antimicrob Chemother. 2012 Mar 5;

Authors: Rottier WC, Ammerlaan HS, Bonten MJ

Abstract
BACKGROUND AND OBJECTIVES: Bacteraemia caused by Enterobacteriaceae (EB) producing extended-spectrum ?-lactamase (ESBL+) has been associated with higher mortality compared with non-ESBL-producing (ESBL-) EB bacteraemia in observational studies. We conducted a systematic review and meta-analysis of these studies to assess how adjusting for confounding in multivariate analyses affects the pooled estimate, and whether multivariate analyses that include intermediates in the causal pathway of outcome (sepsis severity and inadequate empirical therapy) have lower estimates of attributable mortality. DATA SOURCES: PubMed search on 23 November 2010 followed by manually searching reference lists of included studies. STUDY ELIGIBILITY CRITERIA: Cohort studies published in English with separate mortality rates for ESBL+ and ESBL- EB bacteraemia. SYNTHESIS METHODS: Random-effects pooling of unadjusted and adjusted ORs followed by subgroup analyses to explore effects of adjustment procedures on adjusted ORs. RESULTS: The pooled OR for the unadjusted mortality associated with ESBL production was 2.35 (95% CI 1.90-2.91, I(2?)=?42%, 32 studies). The pooled adjusted OR was 1.52 (95% CI 1.15-2.01, I(2?)=?32%, 15 studies). Adjustment for more intermediates was associated with decreasing ORs. The pooled OR for the analyses adjusting for inadequate empirical therapy was 1.37 (95% CI 1.04-1.82). CONCLUSIONS: ESBL production in EB bacteraemia is associated with a higher mortality compared with bacteraemia with ESBL- EB, although the estimate of this association is affected by adjustment procedures. Adjustment for inadequate empirical therapy leads to a reduction in ORs, indicating that higher mortality is likely to be mediated through this phenomenon.

PMID: 22396430 [PubMed - as supplied by publisher]

Altered vancomycin pharmacokinetics in obese and morbidly obese patients: what we have learned over the past 30 years.

J Antimicrob Chemother. 2012 Mar 1;

Authors: Grace E

Abstract
Vancomycin was the first glycopeptide antibiotic introduced into clinical practice. Despite the numerous benefits of vancomycin, clinicians have struggled to dose vancomycin successfully in obese patients to achieve a therapeutic concentration for optimal bacterial killing. Owing to the hydrophilicity of vancomycin and the increase in both adipose tissue and muscle mass associated with obesity, the volume of distribution of vancomycin in obese patients is likely to be altered compared with non-obese patients. In addition to an increase in body mass, obesity is associated with an increase in certain circulating proteins, which results in altered free serum vancomycin concentration. Another alteration that occurs in obesity is increased blood flow secondary to increased cardiac output and blood volume, resulting in increased vancomycin clearance in obese patients. Vancomycin pharmacokinetics in the obese population remain an area of much debate, one that requires continued research given the rising number of obese patients in both the USA and worldwide.

PMID: 22382471 [PubMed - as supplied by publisher]

Transmission of carbapenem-resistant pathogens in New York City hospitals: progress and frustration.

J Antimicrob Chemother. 2012 Feb 29;

Authors: Landman D, Babu E, Shah N, Kelly P, Olawole O, Bäcker M, Bratu S, Quale J

Abstract
OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are endemic in many medical centres. Because therapeutic options are limited, understanding the epidemiology and controlling the spread of these pathogens are of paramount importance. METHODS: Isolates of K. pneumoniae, A. baumannii and P. aeruginosa were collected from 14 hospitals in New York City over a 3 month period in 2009, and analysed for the presence of genes encoding important carbapenemases. Comparisons were made with a similar study conducted in 2006. Demographic and infection control-related information from hospitals was collected. RESULTS: Overall, 29% of K. pneumoniae possessed the carbapenemase KPC, significantly improved from the 38% observed in 2006 (P?<?0.001). However, carbapenem resistance worsened in A. baumannii (mostly due to the emergence of strains with OXA-type carbapenemases) and P. aeruginosa. The decline in KPC-possessing K. pneumoniae was not uniformly observed in all of the hospitals. In a subset analysis of nine hospitals, those with a decreasing prevalence of bla(KPC) had shorter average lengths of stay. CONCLUSIONS: Measurable improvement has occurred in reducing the spread of KPC-possessing K. pneumoniae, and reducing the average length of stay may augment infection control efforts. However, the problem of carbapenem-resistant A. baumannii and P. aeruginosa lingers. New approaches, including respiratory isolation and environmental cleaning, need to be examined to control the spread of A. baumannii and P. aeruginosa.

PMID: 22378678 [PubMed - as supplied by publisher]

Usefulness of corticosteroid therapy during chronic disseminated candidiasis: case reports and literature review.

J Antimicrob Chemother. 2012 Feb 27;

Authors: Chaussade H, Bastides F, Lissandre S, Blouin P, Bailly E, Chandenier J, Gyan E, Bernard L

Abstract
OBJECTIVES: Chronic disseminated candidiasis (CDC) is a disseminated fungal infection that is frequently seen in patients undergoing intensive treatment of haematological malignancies. The first signs of CDC appear during neutrophil recovery. Clinical and physiopathological characteristics of CDC suggest it belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome (IRIS). We report five cases of CDC treated with antifungal therapy and adjuvant corticosteroids to decrease the exacerbated inflammatory response. METHODS: We conducted a retrospective study in the Haematology Department of the University Hospital of Tours, France. The five reported cases were treated for CDC with antifungal therapy and adjuvant corticosteroids. RESULTS: Of the five cases of CDC, one was proven and four were possible, according to the 2008 European Organization for Research and Treatment of Cancer (EORTC) classification. All patients were being treated for acute leukaemia. In all cases, symptoms disappeared 2.8 days (range, 1-7) after the beginning of adjunctive corticosteroid therapy. Corticosteroids were administered on average for 146 days (range, 4 weeks-1 year) and antifungal therapy was administered for the duration of chemotherapy consolidation. There was no exacerbation of CDC symptoms during the next round of chemotherapy or bone marrow transplantation. One patient died from relapse of leukaemia. CONCLUSIONS: Within the framework of IRIS, adjuvant corticosteroid therapy could rapidly improve CDC symptoms and allow continued chemotherapy without delay and without compromising the haematological prognosis.

PMID: 22374323 [PubMed - as supplied by publisher]

Acute kidney injury associated with trimethoprim/sulfamethoxazole.

J Antimicrob Chemother. 2012 Feb 20;

Authors: Fraser TN, Avellaneda AA, Graviss EA, Musher DM

Abstract
OBJECTIVES: Trimethoprim/sulfamethoxazole effectively treats community-acquired soft tissue infections and urinary tract infections, both of which occur in patients with risk factors for renal impairment. We systematically studied the adverse renal effects of trimethoprim/sulfamethoxazole in a middle-aged veteran population. METHODS: We reviewed complete electronic records for all patients who, during a 3 year period, had received ?6 days of treatment with trimethoprim/sulfamethoxazole and for whom a baseline and follow-up determination of serum creatinine and blood urea nitrogen (BUN) were available. RESULTS: Of 573 patients who met inclusion criteria, 64 (11.2%) had increases in both serum creatinine and BUN that met predetermined criteria for acute kidney injury (AKI): in 33 (5.8%), AKI was judged likely due to trimethoprim/sulfamethoxazole; in 28 (4.9%), possibly due to trimethoprim/sulfamethoxazole; and in 3 (0.52%), unrelated to trimethoprim/sulfamethoxazole. Five additional patients (0.9%) had elevations only in serum creatinine. In nearly all cases likely due to trimethoprim/sulfamethoxazole, AKI resolved promptly after discontinuation of therapy, but one patient required dialysis. Pyuria appeared in only 2 of 37 patients who had urinalyses; eosinophiluria was not observed. In a multivariate model, patients with hypertension and diabetes mellitus had increased risk for renal insufficiency, especially if these conditions were considered poorly controlled. CONCLUSIONS: In a middle-aged male inpatient population treated for a minimum of 6 days, AKI is much more common with trimethoprim/sulfamethoxazole therapy than previously reported. Intrinsic renal impairment rather than interstitial nephritis or competition for creatinine clearance appears responsible for the great majority of cases, and neither an effect of dose nor duration was detected in a univariate analysis. Impairment is transient if therapy is discontinued.

PMID: 22351681 [PubMed - as supplied by publisher]

Methicillin-resistant Staphylococcus aureus bacteraemia and endocarditis treated with ceftaroline salvage therapy.

J Antimicrob Chemother. 2012 Feb 6;

Authors: Ho TT, Cadena J, Childs LM, Gonzalez-Velez M, Lewis JS

Abstract
BACKGROUND: One of the newest methicillin-resistant Staphylococcus aureus (MRSA) antibiotics to receive FDA approval is ceftaroline fosamil, a member of a new subclass of cephalosporins with unique activity against MRSA. However, ceftaroline is currently only FDA approved for complicated skin/soft tissue infections and community-acquired pneumonia; there are currently no clinical data regarding its use in MRSA bacteraemia and endocarditis. We report a series of six patients in which ceftaroline was utilized as salvage monotherapy in persistent MRSA bacteraemia or endocarditis. METHODS: Using pharmacy records, 11 ceftaroline-treated patients were identified between January 2011 and November 2011 at University Health System and the South Texas Veterans Health Care System in San Antonio, TX, USA. All cases were reviewed and six patients received ceftaroline therapy for MRSA bacteraemia or endocarditis due to persistent or recurrent bacteraemia while on standard antibiotics (vancomycin or daptomycin). RESULTS: All six patients experienced rapid clearance of their bacteraemia after starting ceftaroline. In the case of endocarditis for which the patient subsequently developed heart failure and required valve replacement, there was no evidence of growth from cultures taken from the excised valve, suggesting sterilization within 13 days of starting ceftaroline. CONCLUSIONS: Ceftaroline exhibits potent anti-MRSA activity in both in vitro and animal studies, including rabbit endocarditis models; however, the lack of clinical data has limited its use in bacteraemia and endovascular infections in humans. We hope that this series serves as an initial stepping stone for further evaluation of this compound for more invasive infections due to MRSA.

PMID: 22311935 [PubMed - as supplied by publisher]

Co-amoxiclav induces proliferation and cytotoxin production of Clostridium difficile ribotype 027 in a human gut model.

J Antimicrob Chemother. 2012 Jan 25;

Authors: Chilton CH, Freeman J, Crowther GS, Todhunter SL, Nicholson S, Wilcox MH

Abstract
OBJECTIVES: Co-amoxiclav is widely prescribed in hospitals. Although reports have suggested it may be linked to onset of Clostridium difficile infection (CDI), data on the risk of CDI associated with specific antibiotics is difficult to obtain, due to confounding clinical factors. We have examined the propensity of co-amoxiclav to induce CDI using a human gut model. METHODS: We used a triple-stage chemostat human gut model to study the effects of co-amoxiclav on indigenous gut microorganisms and C. difficile PCR ribotype 027. C. difficile viable counts and spores were evaluated, and cytotoxin titres were assayed. Co-amoxiclav concentrations were measured using a large plate bioassay. RESULTS: Co-amoxiclav induced rapid C. difficile germination and high toxin production in the gut model, from 5 days after commencement of instillation. Cell proliferation and toxin production were prolonged and continued throughout the duration of the experiment. Only very low levels of co-amoxiclav antimicrobial activity could be detected within the gut model, despite having a marked effect on gut flora microorganisms. CONCLUSIONS: Co-amoxiclav induced CDI within the gut model, supporting clinical observations linking co-amoxiclav treatment with CDI onset. This reinforces the value of the gut model as a clinically relevant means of studying CDI. Caution should be exercised in the prescription of co-amoxiclav to patients in high CDI risk settings.

PMID: 22279183 [PubMed - as supplied by publisher]

Prospective study of severity assessment and management of acute medical admissions with skin and soft tissue infection.

J Antimicrob Chemother. 2012 Jan 9;

Authors: Marwick C, Rae N, Irvine N, Davey P

Abstract
BACKGROUND: Several severity scoring systems have been proposed for skin and soft tissue infections (SSTIs), but none has been tested prospectively. METHODS: We prospectively enrolled adult, acute medical admissions with SSTI between April 2009 and June 2010. Severity was assessed using two proposed SSTI scoring systems, one based on a generic sepsis definition. Antimicrobial prescribing was compared with guideline recommendations. RESULTS: We enrolled 79 patients. One of the scoring systems classified 47% into class I (no sepsis or comorbidity), 5% into class II (no sepsis, but comorbidity), 34% into class III [sepsis, but standardized early warning system (SEWS) <4], and 14% into class IV (sepsis with SEWS ?4). The other system classified 39% as mild and 61% as moderate/severe. There were significant discrepancies between the two scoring systems. Using the worst clinical observations in the first 24 h, 19% of patients had more severe disease than was apparent on admission. Under-treatment of patients with sepsis occurred in 13% of patients according to admission observations, increasing to 22% according to the worst observations. Seventy-nine percent of patients with sepsis received antibiotics within 4 h of admission. This was associated with fewer adverse outcomes (P?=?0.05). CONCLUSIONS: There is significant room for improvement in the management of SSTIs presenting to acute medical units. The added value of specific SSTI severity scores over generic sepsis assessment requires validation in a larger prospective study. We have changed our antibiotics policy for SSTI to use generic sepsis scores, and we emphasize the need to reassess patients on the day of admission.

PMID: 22232513 [PubMed - as supplied by publisher]

Mandatory surveillance of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in England: the first 10 years.

J Antimicrob Chemother. 2012 Jan 4;

Authors: Johnson AP, Davies J, Guy R, Abernethy J, Sheridan E, Pearson A, Duckworth G

Abstract
Since 2001 it has been mandatory for acute hospital Trusts (groups of hospitals under the same management) in England to report all cases of bacteraemia due to Staphylococcus aureus together with information on their susceptibility or resistance to methicillin. This allowed the incidence of methicillin-resistant S. aureus (MRSA) bacteraemia (expressed as the number of cases per 1000 occupied bed days) to be determined for each Trust. In late 2005, the scheme was enhanced to collect demographic, clinical and epidemiological information on each case using a web-based data collection system. Analysis of this mandatory dataset has provided important information on the trends in MRSA bacteraemia in England and has documented a year-on-year decrease in incidence since 2006, following a government initiative in which Trusts were tasked with halving their MRSA bacteraemia rates over a 3year period. In addition, the enhanced mandatory surveillance scheme has captured a wealth of data that have helped to further define the epidemiology of MRSA bacteraemia. It is to be hoped that based on the English experience of mandatory surveillance, other countries will consider the implementation of similar schemes, not only for MRSA but for other pathogens of public health importance.

PMID: 22223229 [PubMed - as supplied by publisher]

A comparative evaluation of adverse platelet outcomes among Veterans' Affairs patients receiving linezolid or vancomycin.

J Antimicrob Chemother. 2011 Dec 15;

Authors: Patel N, Vandewall H, Tristani L, Rivera A, Woo B, Dihmess A, Li HK, Smith R, Lodise TP

Abstract
OBJECTIVES: The primary objectives were to compare the incidences of severe thrombocytopenia, critical thrombocytopenia and a relative decline in platelets from baseline (?50% decline) between patients receiving linezolid and those receiving vancomycin. The secondary objective was to assess the relationship between vancomycin trough concentration and adverse platelet outcomes. METHODS: A matched cohort study was performed at the Upstate New York Veterans' Affairs Healthcare Network from January 2005 until February 2008. Eligibility criteria were: (i) receipt of linezolid or vancomycin therapy for ?48 h; (ii) initiation of therapy as an inpatient; and (iii) baseline platelets available for evaluation. Patients who received linezolid were matched 1?:?1 to patients who received vancomycin. Cumulative incidences and times to event for (i) platelet count ?50?000 cells/mm(3), (ii) platelet count ?20?000 cells/mm(3) and (iii) ?50% decline in platelets from baseline were evaluated. Multivariate analyses were performed. RESULTS: The study included 502 patients (251 matched pairs). The occurrences of platelet counts ?50?000 cells/mm(3) and ?20?000 cells/mm(3) did not differ significantly between linezolid and vancomycin patients. A ?50% decline in platelets from baseline was observed in 78 (31.1%) patients receiving vancomycin and 43 (17.1%) patients receiving linezolid (risk ratio 0.55; 95% CI 0.40-0.77). A clear exposure-response relationship was observed between vancomycin trough concentration and ?50% decline in platelets from baseline. CONCLUSIONS: The incidence of thrombocytopenia was low and did not differ significantly among vancomycin and linezolid patients.

PMID: 22174041 [PubMed - as supplied by publisher]

Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics.

J Antimicrob Chemother. 2011 Dec 6;

Authors: Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ

Abstract
BackgroundClostridium difficile infections (CDIs) are common in developed countries and affect >250?000 hospitalized patients annually in the USA. The most important risk factor for the disease is antibiotic therapy.MethodsTo determine the period at risk for CDI after cessation of antibiotics, we performed a multicentre case-control study in the Netherlands between March 2006 and May 2009. Three hundred and thirty-seven hospitalized patients with diarrhoea and a positive toxin test were compared with 337 patients without diarrhoea. Additionally, a control group of patients with diarrhoea due to a cause other than CDI (n?=?227) was included.ResultsIn the month prior to the date of inclusion, CDI patients more frequently used an antibiotic compared with non-diarrhoeal patients (77% versus 49%). During antibiotic therapy and in the first month after cessation of the therapy, patients had a 7-10-fold increased risk for CDI (OR 6.7-10.4). This risk declined in the period between 1 and 3 months after the antibiotic was stopped (OR 2.7). Similar results were observed when the second control group was used. All antibiotic classes, except first-generation cephalosporins and macrolides, were associated with CDI. Second- and third-generation cephalosporins (OR 3.3 and 5.3, respectively) and carbapenems (OR 4.7) were the strongest risk factors for CDI. Patients with CDI used more antibiotic classes and more defined daily doses, compared with non-diarrhoeal patients.ConclusionsAntibiotic use increases the risk for CDI during therapy and in the period of 3 months after cessation of antibiotic therapy. The highest risk for CDI was found during and in the first month after antibiotic use. Our study will aid clinicians to identify high-risk patients.

PMID: 22146873 [PubMed - as supplied by publisher]