Judith R. Campbell

Emergence of New Strains of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit

BACKGROUND Genetically distinct strains of methicillin-resistant Staphylococcus aureus (MRSA) of community rather than hospital origin have emerged in many areas of the United States. We determined if MRSA strains causing bacteremia in infants treated from birth in a neonatal intensive care unit (NICU) demonstrated the genetic traits of community-associated MRSA. METHODS A retrospective cohort study was conducted among NICU infants with bacteremia due to MRSA during 2003 in a large tertiary care center NICU in Houston. MRSA isolates were characterized by antimicrobial susceptibility testing and staphylococcal cassette chromosome mec (SCCmec) typing by polymerase chain reaction. All MRSA cases were reviewed for clinical severity of infection and outcome. RESULTS During 2003, a total of 8 (47%) of 17 infants with bacteremia due to S. aureus had MRSA infection. Isolates from 6 (75%) of these 8 infants carried the SCCmec genes (class B mec and ccr2) that are characteristic of community MRSA; 4 isolates were type IVa. All 6 isolates were resistant to beta-lactam antibiotics and erythromycin; 1 was also resistant to clindamycin. One isolate was nontypeable, and another carried the SCCmec type II gene (typical of hospital-associated strains) and was susceptible only to vancomycin. Seven (88%) of 8 infants presented in septic shock. Despite initial treatment with vancomycin, 3 (38%) died, and 3 survivors had complications requiring prolonged antimicrobial therapy; these 6 infants had MRSA isolates with genetic characteristics of isolates of community origin. CONCLUSIONS Community-associated MRSA strains have emerged as a significant cause of sepsis in neonates hospitalized in NICU since birth and have caused disseminated infection with substantial morbidity and mortality.

Group B streptococcal colonization and serotype-specific immunity in pregnant women at delivery.

Objective To describe the relationship between serum concentration of group B streptococcal capsular polysaccharide–specific immunoglobulin (Ig) G, colonization status, race or ethnicity, and age in pregnant women. Methods Pregnant women (n = 3307) were enrolled from geographically and ethnically diverse populations. At the time of admission for delivery, swabs of the lower vagina and rectum were obtained for isolation of group B streptococci. In a subset of women whose sera were available, capsular polysaccharide–specific IgG concentrations were quantified by serotype-specific (Ia, Ib, II, III, and V) enzyme-linked immunosorbent assay and compared by group B streptococcal colonization status. Results Group B streptococcal colonization was detected in 856 women (26%), and the rate was significantly higher among black women (37%) than in other racial or ethnic groups (odds ratio 1.7, 95% confidence interval 1.4, 2.1). Colonization status did not differ by study site or age. Colonization with serotypes Ia, II, III, or V was associated with significantly higher serum concentrations of IgG specific for the capsular polysaccharide of the colonizing serotype compared with noncolonization. However, 48% of colonized women had low capsular polysaccharide–specific IgG levels (less than 0.5 μg/mL) in their delivery sera. Colonized teenagers had the lowest median concentration. Conclusion Colonization with group B streptococcus can elicit a systemic immune response, with a cumulative increase in the prevalence of capsular polysaccharide–specific IgG with increasing age. Conversely, low antibody levels in colonized teenagers might account in part for the reported increased risk of group B streptococcal disease in neonates born to these patients.

Fluconazole Prophylaxis in Extremely Low Birth Weight Neonates Reduces Invasive Candidiasis Mortality Rates Without Emergence of Fluconazole-Resistant Candida Species

OBJECTIVE. We evaluated the impact of fluconazole prophylaxis for extremely low birth weight infants on invasive candidiasis incidence, invasive candidiasis-related mortality rates, and fluconazole susceptibility of Candida isolates. METHODS. Extremely low birth weight infants <5 days of age, except those with liver dysfunction, were eligible for fluconazole prophylaxis. NICU infants (all birth weights) with invasive candidiasis between April 2002 and March 2006 were compared with those with invasive candidiasis before fluconazole prophylaxis (2000–2001). RESULTS. Twenty-two infants had invasive candidiasis (all candidemia) during fluconazole prophylaxis; before fluconazole prophylaxis, there were 19 cases (candidemia: 17 cases; meningitis: 2 cases). Invasive candidiasis incidence in NICU infants decreased from 0.6% (19 of 3012 infants) before fluconazole prophylaxis to 0.3% (22 of 6393 infants) in 2002–2006 and that in extremely low birth weight infants decreased 3.6-fold. No Candida-attributable deaths occurred during 2002–2006 fluconazole prophylaxis, compared with 4 (21%) before fluconazole prophylaxis. The onset of invasive candidiasis was later during 2002–2006 (23.5 vs 12 days), but risk factors were similar. The invasive candidiasis species distribution remained stable. Of 409 infants who received fluconazole prophylaxis, 119 (29%) received 42 days. Shorter fluconazole prophylaxis duration was related to intravenous access no longer being necessary in 242 cases (59%), noninvasive candidiasis-related death in 29 (7%), hospital transfer in 8 (2%), invasive candidiasis diagnosis in 8 (2%), and transient increase in serum transaminase levels in 4 (1%). One hundred twenty-seven infants (31%) who received fluconazole prophylaxis developed cholestasis during hospitalization, two thirds of whom had other predisposing conditions. On multivariate logistic regression necrotizing enterocolitis and increasing days of total parenteral nutrition, but not increasing number of doses on days of fluconazole, were significantly associated with the development of cholestasis. CONCLUSION. During 4 years of fluconazole prophylaxis, the incidence of invasive candidiasis and invasive candidiasis-associated mortality rates in extremely low birth weight infants were reduced significantly, without the emergence of fluconazole-resistant Candida species.

Influenza A virus outbreak in a neonatal intensive care unit.

BACKGROUND Nosocomial infections with influenza virus are rarely recognized in neonatal intensive care units (NICU). An outbreak of influenza A virus infection in the NICU of an urban county hospital during the 1997 to 1998 influenza season is reported. METHODS Clinical and virologic data were recorded in all symptomatic NICU patients after influenza A infection was diagnosed in one infant in October, 1997. RESULTS Influenza A/H3N2 was isolated from two of four symptomatic infants. The application of rapid diagnostic techniques for the characterization of influenza virus infection allowed the timely institution of basic infection control measures, limiting this outbreak. Resistance to amantadine was documented for the first time in this patient population by reverse transcription-PCR within 48 h of treatment in one case. CONCLUSIONS Prevention by immunization is a priority in those caring for high risk NICU patients.

Features of Invasive Staphylococcal Disease in Neonates

Objective. Most clinical descriptions of invasive staphylococcal disease (ISD) in neonates date from before the mid-1980s, when neonatal viability and intensive care differed substantially from current standards. We aimed to describe the contemporary incidence, clinical features, and outcome of infants with ISD in a neonatal intensive care unit. Methods. A retrospective cohort study was conducted of infants who had ISD and were in the neonatal intensive care unit of the Womans Hospital of Texas, Houston, from January 2000 to June 2002. Confirmed ISD was defined as clinical sepsis and Staphylococcus aureus (SA) isolated from ≥1 blood culture (BC) or a sterile body site excluding urine or coagulase-negative staphylococci (CoNS) isolated from ≥2 BC or from 1 BC and a sterile body site. Probable ISD was defined as CoNS isolated from 1 BC or a sterile body site for which clinical and laboratory data review by 3 infectious disease specialists indicated that antimicrobial treatment was appropriate. Confirmed and combined confirmed plus probable cases were analyzed. Results. A total of 149 episodes (83 confirmed [39 SA, 44 CoNS], 66 probable) in 137 infants (mean gestational age [GA]: 27.6 weeks [22.4–36.4]; mean birth weight: 981 g [350–2995]) were reviewed. Four (3%) infants had early-onset infection (2 SA, 2 CoNS). Median age at infection onset was similar (17 days SA; 18 days CoNS). Intravascular catheters (IVC) were in situ in a minority of infants with ISD episodes (38% SA, 43% CoNS). CoNS more than SA infections were associated with very low birth weight (<1500 g), lower GA, a history of more IVCs and concurrent total parenteral nutrition, but IVC and parenteral nutrition days were similar. By multivariate analysis correcting for birth weight and complications of prematurity, hypoxia at the time of sepsis evaluation was significantly associated with CoNS and hypotension with SA infections; other clinical features were similar. Methicillin-resistant SA caused 8% of SA infections. Among bacteremic infants, SA more frequently than CoNS involved ≥2 sites. Overall, SA had more focal complications (primarily bone and joint) than CoNS, resulting in a 2- to 3-fold higher SA-associated morbidity rate. Mortality directly attributable to either organism was similar (5% SA; 5% confirmed, 3% confirmed/probable CoNS). Conclusion. CoNS ISD occurred in smaller, more premature infants than SA and was IVC associated in a minority of cases. Hypoxia and hypotension were the only presenting features that differentiated CoNS and SA. SA-associated morbidity was substantial, but SA infection carried no greater risk of death (5%) than CoNS.

An outbreak of M serotype 1 group A Streptococcus in a neonatal intensive care unit

OBJECTIVE To describe the investigation and control of an outbreak of M serotype 1, Streptococcus pyogenes (group A Streptococcus, GAS) infections in a neonatal intensive care unit (NICU). STUDY DESIGN The study was conducted in an NICU in a large urban university-affiliated hospital. Retrospective review was performed of all infants and health care workers in the NICU, especially those either colonized or infected with GAS during the outbreak and the prospective surveillance period (July through September 1994). Prospective epidemiologic investigation, including cultures of throat, umbilicus, and anorectum (infants), or throat and anus (NICU personnel), identified a possible common source of the disease in case infants. Antimicrobial susceptibility testing and serotyping of all GAS strains were performed; M serotype 1 isolates were examined by DNA analysis with restriction fragment length polymorphism. The M-1 GAS isolates were tested for streptococcal pyrogenic exotoxin (SPE) A and SPE B production. A retrospective chart review and analysis of infants with GAS infection or colonization was conducted. RESULTS During a 1-week period, two very low birth weight infants more than 3 weeks of age had GAS septicemia and focal infection. Two additional very low birth weight infants with asymptomatic throat colonization were identified during the first week of surveillance. Benzathine penicillin G was administered to all NICU infants, but failed to eradicate throat colonization in the four case subjects. Seven days after completing parenteral antibiotic therapy, the index patient had a recurrence of GAS septicemia that was fatal. Eradication of throat colonization in the remaining three infants was achieved with a 10-day course of intravenous clindamycin therapy. Among 103 NICU personnel, five (4.9%) had asymptomatic GAS colonization with strains that were uniformly susceptible to penicillin. Each colonized adult was successfully treated with oral clindamycin therapy. Serotyping revealed that five isolates of GAS from four infants and one NICU respiratory therapist were M-1 isolates; DNA analysis confirmed that these were the same strain. The five M-1 isolates produced both SPE A and SPE B. CONCLUSIONS The previously documented increase in prevalence of M-1 strains of GAS in the United States is likely to be associated with their introduction into closed populations including NICUs. Control of such outbreaks may be achieved by isolation, cohorting of case subjects and possible carriers, and successful eradication of colonization in case subjects and carriers. Although GAS organisms are uniformly susceptible to penicillin G, eradication may require agents other than penicillin.

Distinguishing true coagulase-negative Staphylococcus infections from contaminants in the neonatal intensive care unit

Objective:To characterize true coagulase-negative Staphylococcus (CoNS) infections in infants receiving neonatal intensive care.Study Design:Retrospective cohort study of neonatal intensive care unit (NICU) infants with clinical sepsis and CoNS isolated from ⩾2 blood cultures (BCs) or one BC and a sterile site (proved infection) or CoNS isolated from one BC and deemed significant after blinded data review (probable infection).Result:In all, 98% of 40 proved and 96% of 55 probable infections occurred in infants with birth weight (BW) <2000 g and gestation <34 weeks. Total central lines (CLs) placed, but not CL duration or presence in situ, predicted proved (odds ratio (OR) 3.5, 95% confidence interval (CI) 1.4 to 8.3; P=0.005) and probable infection (OR 2.7, 95% CI 1.3 to 5.6; P=0.007) by multivariate analysis as did lethargy and gastric residuals.Conclusion:True CoNS infection is unlikely in infants with BW >2000 g and gestation >34 weeks. Total CL required for care, lethargy and gastric residuals predicted true CoNS infection.

Trichosporonosis, an unusual fungal infection in neonates.

Trichosporon asahii, formerly known as Trichosporon beigelii, is a ubiquitous yeast found naturally in soil and in stagnant or fresh water. It causes superficial infection of the hair shafts, commonly referred to as white piedra. Other superficial infections caused by T. asahii include onychomycosis and otomycosis. Deep infections caused by T. asahii, known as trichosporonosis, occur most often in patients with underlying immunocompromising conditions such as cytotoxic chemotherapy-induced granulocytopenia, hemochromatosis, AIDS or steroid-induced altered immune function. In these patients infection may be limited to a single organ site or may become disseminated. Reports of T. asahii colonization or invasive disease in very low birth weight (VLBW) neonates are rare. Most reported cases have been associated with an outbreak in one neonatal intensive care unit. These infections are almost uniformly fatal in these neonatal immunocompromised hosts. We report two neonates with trichosporonosis and review the possible underlying risk factors, clinical presentation, management and outcome for our patients and those reported previously in the literature.

Clinical and Molecular Features of Decreased Chlorhexidine Susceptibility among Nosocomial Staphylococcus aureus Isolates at Texas Children's Hospital

ABSTRACT One of the strategies utilized to decrease infections in the hospital setting relies on topical antimicrobials and antiseptics. While their use is beneficial, concerns arise over the potential to develop resistance or tolerance to these agents. We examined nosocomial Staphylococcus aureus isolates from 2007 to 2013 for the presence of genes associated with tolerance to chlorhexidine. Isolates and patients were identified from an S. aureus surveillance study at Texas Childrens Hospital. Nosocomial S. aureus isolates (those causing infection at ≥72 h of hospitalization) were identified and underwent PCR for the qacA or qacB (qacA/B) and smr genes associated with elevated minimum bactericidal concentrations of chlorhexidine. Molecular typing with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and agr typing and a review of the medical record were performed. Two hundred forty-seven nosocomial S. aureus infections were identified. Overall, 111 isolates carried one or both genes (44.9%); 33.1% were positive for smr, 22.7% were positive for qacA/B, and 10.9% of the isolates possessed both genes. The smr-positive isolates were more often resistant to methicillin, ciprofloxacin, and/or clindamycin. The isolates positive for qacA/B were more often associated with indwelling central venous catheters and a vancomycin MIC of ≥2 μg/ml. Isolates carrying either smr or qacA/B were associated with a diagnosis of bacteremia. The smr-positive isolates more often belonged to sequence type 8 (ST8) than the isolates that were positive for qacA/B. Mupirocin resistance was detected in 2.8% of the isolates. Antiseptic-tolerant S. aureus strains are common in our childrens hospital and are associated with decreased susceptibility to other systemic antimicrobials and with bloodstream infections. Further work is needed to understand the implications that these organisms have on the hospital environment and antiseptic use in the future.

Cluster of Bacillus species bacteremia cases in neonates during a hospital construction project.

We report an outbreak of Bacillus bacteremia among premature infants during a construction project. Our investigation revealed potential environmental sources. After replacement of air filters, cleaning of the unit, emphasis on hand hygiene, and relocation of the loading dock for linen and supply delivery, no further cases were detected.