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SummaryThe clinical and economic burden of adult community-acquired pneumonia (CAP) in Latin America is not well known. We conducted a literature review to describe the etiology, incidence, hospitalization, morbidity and mortality, antibiotic resistance, costs associated with care, and the potential benefits of pneumococcal vaccination in the reduction of adult CAP in Latin America. Data that were published during the period from January 1970 through August 2008 were identified via the Web sites and databases of the Pan American Health Organization, Latin American health agencies, and the US National Institutes of Health, National Library of Medicine (MEDLINE). Streptococcus pneumoniae was identified as the most common pathogen, accounting for up to 35% of CAP cases. The mean rate of CAP due to penicillin-resistant S. pneumoniae was 39%. The mortality in Latin America due to lower respiratory tract infections has been reported to be 6%, compared with 4% in developed regions, and CAP was the third most frequent cause of death in adults in 31 Latin American countries in 2001–2003. Although S. pneumoniae caused the majority of CAP, similar to other regions of the world, mortality due to CAP in Latin America was substantially greater than that in developed countries. This review demonstrates the need to facilitate standardized surveillance and reporting systems to monitor the burden of CAP and to implement prevention strategies to decrease the clinical and economic burden of CAP in Latin American adults.

Poster: "18th ICID / UMP.305 / Distribution of Streptococcus pneumoniae serotypes in isolates collected from sterile body sites in the United States (US), 2004-2015" by: "K. Kazmierczak 1, M. Hackel1, H. li1, B. Hilton2, R. Isturiz2, H. sings2; 1Schaumburg, IL/US, 2Collegeville, PA/US"

Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious threat to public health worldwide. Ongoing surveillance is essential to support infection control committees and clinicians in the prevention and treatment of infection. However, in Latin America, resources for monitoring the changing epidemiology of MRSA remain limited. In this article, we review the current situation of MRSA in Latin America in order to highlight the need for a more harmonised effort to improve its management. Literature in the PubMed and SciELO databases as well as the website of the Pan American Health Organization were searched for articles and information about the epidemiology of MRSA in Latin America. MRSA is already the leading cause of nosocomial infection in the Latin American region, and the number of reports of community-acquired MRSA infections is also rising. However, the extent of the problem is not fully understood, especially since data tend to come from large hospitals whereas much of the population is served by small community healthcare centres that do not have extensive facilities for performing microbiological surveillance. In conclusion, wider-reaching and co-ordinated programmes to provide regular MRSA surveillance reports are required across the Latin American region.

Globally, antibiotic resistance continues to be an increasing problem. The emergence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and extended spectrum β-lactamase-producing Enterobacteriaceae has seriously reduced the number of empirical agents suitable for selected indications. Increasing Gram-negative resistance has also negatively impacted the physician's alternatives when choosing adequate initial therapy; increased reliance on the carbapenem class as empirical agents has led to the emergence of multidrug resistance in non-enteric Gram-negative bacilli. There is a critical need for new, broad-spectrum alternatives to the currently available broad-spectrum agents.

Streptococcus pneumoniae is a leading cause of illness and death in adults. A polysaccharide vaccine has been available for over 30 years, but despite significant use, the public health impact of this vaccine has been limited. The 13-valent pneumococcal conjugate vaccine (PCV13) has been licensed by the US Food and Drug Administration and other international regulatory authorities with the assumption that induction of a T cell-dependent immune response and noninferior immunogenicity to vaccine antigens when compared with the polysaccharide vaccine would be important to satisfy a significant unmet medical need. PCV13 efficacy against vaccine-type pneumococcal community-acquired pneumonia was confirmed in a large randomized controlled trial in older adults and its use is now increasingly recommended globally.

Because all important assumptions used in the model are simultaneously biased toward PCV10, the model results are erroneous and misleading. Routine infant pneumococcal vaccination in Japan would undoubtedly bring substantial reductions in morbidity and mortality. However, given the current epidemiologic landscape in Japan and the current evidence, the clinical and economic gains from the use of PCV13 would, undoubtedly, far exceed those potentially observed from the use of PCV10. We urge those who conduct, critique, and consider cost-effectiveness studies to evaluate the strength of the evidence of clinical claims for the products and the influence these assumptions have on the overall findings. In addition, when performing economic predictive modeling, it is critical to provide a balanced perspective by weighing the strengths and weaknesses of all available data to construct the base case analysis.

Sirs:We appreciate the opportunity to respond to Dr Fedson’s reply1 to our letter2 in which we stated that effectiveness of polysaccharide pneumococcal vaccines for the prevention of non-invasive p...

Background In the fall of 2014, the Advisory Committee on Immunization Practices (ACIP) recommended 13-valent pneumococcal conjugate vaccine (PCV13) for all US adults age ≥65 years. Coverage rates are currently unknown. This study estimated overall PCV13 coverage rates in older adults and determined if disparities in uptake existed for some sociodemographic groups. Methods A monthly series (August 1, 2014 – Feb 28, 2017) of cross-sectional analyses of administrative diagnosis and prescription claims data collected by QuintilesIMS and linked to sociodemographic data collected by Experian were used to estimate overall and subpopulation-level uptake of PCV13 among US adults age ≥65. Uptake estimates were adjusted to PCV13 manufacturer sales data to account for missingness patterns in QuintilesIMS claims data. Univariate and multivariable analyses of PCV13 uptake were performed across sociodemographic factors (e.g., race/ethnicity, household income, neighborhood urbanicity, education status). Results Among adults age ≥65, 50% received PCV13 by the end of February 2017. Disparities in PCV13 uptake were apparent. Black adults (39%) and Hispanics (32%) (vs. 53% for whites), the poor (36% vs. 64% for lowest vs. highest income deciles), adults with low educational status (37% vs. 58% for those without high school education vs. college educated), and those living in rural (33%) or urban/inner city (41%) areas (vs. 52% in suburban areas) had significantly lower PCV13 uptake (all P < .001) (Figure). These differences persisted in multivariable analyses. Conclusion PCV13 uptake among adults age ≥65 occurred rapidly after ACIP recommendation in late 2014. Yet, poor and minority communities, rural and urban/inner city areas, and communities with low educational attainment may need more time to adequately implement adult vaccine guidelines following ACIP recommendation. In 2018, current adult pneumococcal recommendations will be revisited by ACIP. Changes to existing recommendations for older adults, however, could cement these disparities in adult PCV13 uptake in the very communities at increased risk for pneumococcal disease. These vulnerable communities may instead benefit from targeted and tailored interventions to increase pneumococcal vaccination. Disclosures J. McLaughlin, Pfizer Inc: Employee and Shareholder, Salary; F. Khan, Pfizer Inc: Employee and Shareholder, Salary; A. Curry, Pfizer Inc: Employee and Shareholder, Salary; V. Snow, Pfizer Inc: Employee and Shareholder, Salary; R. Isturiz, Pfizer Inc: Employee and Shareholder, Salary; D. Swerdlow, Pfizer Inc: Employee and Shareholder, Salary

Background The implementation of pneumococcal conjugate vaccination (PCV) in children with the 7-valent and 13-valent PCV in 2000 and 2010, respectively, has reduced the incidence of pneumococcal disease, nasopharyngeal carriage and changed the epidemiology of S. pneumoniae serotypes (STs). This study describes the yearly trends in antimicrobial non-susceptibility (NS) rates in pneumococci during 2009–2015. Methods 6,197 S. pneumoniae originated from patients (≥18 years old) seen/hospitalized in 105 US sites and recovered primarily (78.3%; 4,852/6,197) from lower respiratory tract specimens. Identification was performed by biochemical algorithms and/or PCR, and susceptibility (S) testing used broth microdilution. MIC interpretation applied CLSI criteria. The cpsB sequence was obtained by PCR or whole genome sequencing for STs determinations. Multiplex PCR and/or Quellung reactions were also performed, as needed. Results All isolates were highly S to levofloxacin (98.7–99.2%), vancomycin (100.0%), and linezolid (100.0%). PCV7 STs showed a reduction in the NS rates for penicillin G (PEN; from 30.3% in 2009 to 16.0% in 2015) and ceftriaxone (CRO; from 27.3% to 12.0%), as did PCV13 STs (from 34.5% to 16.0%% and from 27.5% to 8.6%, respectively). ST 19F showed stable S patterns over time and 19A remained the less S ST with high NS rates for PEN (49.0%–76.5%), CRO (24.5–64.8%), erythromycin (ERY; 76.9–90.8%), and clindamycin (CLI; 51.0–73.1%). These NS rates for 19A rose from 2009 to 2011–2012, decreasing in 2013–2016. NS rates for CLI and ERY against ST 3 increased to 19.6% and 23.9% in 2015, respectively. Non-vaccine STs showed stable NS rates for PEN, CRO, and CLI. However, an increasing trend for ERY NS (from 35.2% in 2009 to 45.0% in 2015) was noted, which was driven by increasing NS rates for 35B (from 42.3% in 2009 to 71.2% in 2015). Conclusion PCV13 ST exhibited decreasing trends for NS during the study period, except for ST 3, which showed stable S rates over time. Overall, implementation of PCV13 decreased considerably the NS rates in S. pneumoniae causing infections in the US adult population. Further surveillance will enhance understanding of future antimicrobial patterns in S pneumoniae in the context of adult pneumococcal vaccination programs. Disclosures R. E. Mendes, Pfizer, Inc.: Research Contractor, Research grant; H. L. Sings, Pfizer, Inc.: Employee, Salary; J. A. Suaya, Pfizer, Inc.: Employee, Salary; L. N. Woosley, Pfizer, Inc.: Research Contractor, Research grant; R. K. Flamm, Pfizer, Inc.: Research Contractor, Research grant; R. E. Isturiz, Pfizer, Inc.: Employee, Salary

This study was conducted to determine the serotype distribution and trends over time of Streptococcus pneumoniae strains associated with noninvasive infections among adult patients ≥18 years of age in the United States (2009 to 2012). A total of 2,927 S. pneumoniae isolates recovered from patients presenting with respiratory infections and obtained mainly (87.0%) from lower respiratory tract specimens (sputum) were included. The levels of the 7-valent pneumococcal conjugate vaccine (PCV7) serotypes remained stable over the 4-year study period (4.6% to 5.5%; P = 0.953). Overall, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were identified in 32.7% of samples, declining from 33.7% to 35.5% in 2009 to 2011 to 28.2% in 2012 ( P = 0.007), with a significant decrease in the levels of serotypes 7F ( P = 0.013) and 6A ( P = 0.010). The levels of 19A remained constant (15.8% to 17.1%) during 2009 to 2011, dropping to 12.2% in 2012 ( P = 0.089). The prevalence of serotypes associated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23), but not PCV13, remained generally stable; however, the prevalence of serotypes 15B and 15C (15B/15C) increased from 2.7% to 6.3% ( P = 0.010). The proportion of nonvaccine serotypes increased gradually during the study period ( P = 0.044), particularly for serotype 35B (from 3.6% in 2009 to 8.2% in 2012; P = 0.001). Nonsusceptibility rates for penicillin (susceptible breakpoint, ≤2 μg/ml) and clindamycin against PCV7 serotypes decreased over the period. These results suggest the emergence of indirect effects following introduction of PCV13 for infants and young children; continued surveillance is needed to assess the burden of PCV13 serotypes in the adult population after the implementation of age-based recommendations in the United States.

Background Recommendations for adult pneumococcal immunization generally specify the use of PCV13 first, followed by PPSV23, when administered sequentially, for prevention of pneumococcal disease. This is supported by observations of reduced functional opsonophagocytic assay (OPA) antibody titers in subjects who received PPSV23 first compared with PCV13 first. Methods In a previously-published phase 3 study of pneumococcal vaccine–naïve adults 60–64 years of age, participants received PCV13 followed by PPSV23 one year later (PCV13/PPSV23) or PPSV23 followed by PCV13 one year later (PPSV23/PCV13). Here we report the previously unpublished clinically relevant comparisons for the 2 sequential dosing groups by showing the antibody response curve analyses by serotype. We also highlight the reverse cumulative distribution curve (RCDC) analysis by serotype for the 2 relevant sequential dosing groups. Results OPA titers for shared serotypes rose substantially from pre-vaccination to 1 month post-initial vaccination for both groups. For all serotypes, OPA titers declined over the year interval between vaccinations, but remained higher at the pre-vaccination 2 time point compared with baseline for both groups. When evaluating the antibody response curves, the OPA geometric mean titers (GMTs) were generally higher for all shared serotypes at all measured time points in the PCV13/PPSV23 group compared with the PPSV23/PCV13 group; example serotype 19F (Figure 1). RCDC analyses show that for the PCV13/PPSV23 group, OPA titers after vaccination 2 were generally higher across the full range of responses than for PPSV23/PCV13; example serotype 19F (Figure 2). Conclusion The observed immune responses, with the sequential administration of PCV13 followed by PPSV23 one year later (PCV13/PPSV23), are higher compared with responses observed with PPSV23 followed by PCV13 one year later (PPSV23/PCV13). This supports the administration of PCV13 first when use of both pneumococcal vaccines is appropriate. Limitations: This study was not designed to determine the optimal interval between PCV13 and PPSV23 doses. Disclosures E. Chilson, Pfizer Inc: Employee and Shareholder, Salary; B. Atkinson, Pfizer Inc: Shareholder, Salary; C. Hall-Murray, Pfizer, Inc.: Employee and Shareholder, Salary; V. Snow, Pfizer Inc: Employee and Shareholder, Salary; B. Schmoele-Thoma, Pfizer Inc: Shareholder, Salary; R. E. Isturiz, Pfizer, Inc.: Employee, Salary; D. A. Scott, Pfizer Inc: Shareholder, Salary

Human immunodeficiency virus (HIV) type 1 and 2 (HIV-1 and HIV-2) infections have had a profound impact on morbidity and mortality worldwide. AIDS has evolved from an illness of men who have sex with men and of injection drug users into a large and expanding pandemic of heterosexually transmitted disease affecting men, women, and children across the globe. This chapter concentrates on the interaction between HIV-1, immune suppression and reconstitution, and opportunistic microbes such as Pneumocystis carinii, Toxoplasma gondii, and Leishmania species.

The global spread of dengue fever within and beyond the usual tropical boundaries threatens a large percentage of the world's population, as human and environmental conditions for persistence and even spread are present in all continents. The disease causes great human suffering, a sizable mortality from dengue haemorrhagic fever and its complications, and major costs. This situation has worsened in the recent past and may continue to do so in the future. Efforts to decrease transmission by vector control have failed, and no effective antiviral treatment is available or foreseeable on the immediate horizon. A safe and effective vaccine protective against all serotypes of dengue viruses is sorely needed.

Four serotypes of dengue viruses produce dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. They are the most important arbovirus infections of humans, in terms of both morbidity and mortality, constituting one of the most rapidly expanding and re-emerging infectious disease problems in Latin America. In less than 20 years, the region has transformed itself from hypoendemic to hyperendemic, while serotype circulation in most countries has gone from none or single to multiple. Changes in endemicity have coincided with the emergence and increasing incidence of the severer forms of dengue infection. This article reviews the clinical presentations of these diseases. Health care providers who see patients in or returning from areas of Latin America, the Caribbean, and other tropical areas must consider dengue in the differential diagnosis of patients presenting with compatible symptoms, and must be knowledgeable in the current management of this important disease.

Background A pneumococcal polysaccharide vaccine (PPSV23) has been available for use in adults ≥65 years old since 1983 with vaccination rates of ~65% in the past decade. A conjugate vaccine (PCV13) has been recommended for adults since 2014, and for children since 2010 (replaced PCV7 which was used since 2000). The serotype distribution of pneumococci causing infections in adult patients in the US was evaluated. Methods 6,491 S. pneumoniae isolates were collected from patients (≥18 years old) seen/hospitalized in 105 US centers and recovered primarily (77.8%; 5,052/6,491) from lower respiratory tract specimens. Identification was performed by biochemical algorithms and/or PCR. The cpsB sequence was obtained by PCR or next genome sequencing for serotype determination. Multiplex PCR and/or Quellung reaction were performed, as needed. Results 19F was the most prevalent PCV7 serotypes with annual rates of 1.6–3.1%, but no trends were observed for this serotype during the period. Overall, PCV13 serotype prevalence declined considerably from 38.6% in 2009 to 23.1% in 2016, but rates remained stable during 2013–2016 (21.5–24.6%). Serotype 19A (12.4%) and 3 (9.1%) were the most common PCV13 serotypes (2009–2016), followed by 7F (2.4%). Prevalence of 19A and 7F declined from 17.5% to 7.1% and from 4.6% to 0.7%, respectively, while the prevalence of serotype 3 remained stable. The proportion of non-vaccine serotypes increased, as did PPSV23 (non-PCV13). Among non-vaccine serotypes, 35B (8.1%), 23A (6.2%), and 6C/6D (5.8%) were the most common, followed by 23B (4.8%) and 15A/15F (4.8%). Prevalence of serotype 35B (from 3.9% to 12.6%) and 23B (from 3.7% to 7.8%) increased considerably during the study period. Serotypes 23A and 15A/15F remained stable throughout; however, serotype 6C/6D decreased from 7.6% to 3.4%. Conclusion Prevalence of serotype 19F remained low and stable during the study period. PCV13 serotypes declined considerably, but serotypes 19A and 3 remained elevated. The consistent increase of non-vaccine serotypes, especially 35B, may be a reason for concern since it exhibits decreased susceptibility to β-lactams. Continued surveillance is needed to constantly assess the dynamic changes of serotypes affecting the adult US population. Disclosures R. E. Mendes, Pfizer, Inc.: Research Contractor, Research grant; H. L. Sings, Pfizer, Inc.: Employee, Salary; B. Hilton, Pfizer, Inc.: Employee, Salary; T. P. Doyle, Pfizer, Inc.: Research Contractor, Research grant; L. N. Woosley, Pfizer, Inc.: Research Contractor, Research grant; R. K. Flamm, Pfizer, Inc.: Research Contractor, Research grant; R. E. Isturiz, Pfizer, Inc.: Employee, Salary

Practical and precise information about the potential infectious health hazards that travelers to Latin America may encounter is reviewed in this article. Some diseases are briefly described, others are only mentioned. The countries have been grouped into four geographical areas following the classification of the World Health Organization. The discussion on each area includes information on travelers' diarrhea, malaria, cholera, typhoid fever, yellow fever, and other diseases or special problems.

Fungal infections remain a frequent health problem in Latin American countries. Although these diseases exhibit an extraordinary heterogeneity, they have certain features in common. Most patients belong to low socioeconomic groups and live in rural areas. This article presents a general view of the most prevalent subcutaneous mycoses, with emphasis on epidemiology, clinical manifestations, laboratory diagnosis, and treatment options in the developing countries of Latin America.

Antimicrobial resistance in Latin America and the Caribbean is widespread and is a limitation for proper treatment of both community- and hospital-acquired infections. Resistance to respiratory pathogens such as Streptococcus pneumoniae and Escherichia coli from urinary tract infections is prevalent throughout the region in ambulatory patients with infections. High rates of resistant to antibiotics used in hospital-acquired infections is a growing threat, including MRSA, ESBL-producing Enterobacteriaceae and carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii.

Hollingsworth and Isturiz1 have raised several questions about our earlier review of the use of pneumococcal conjugate (PCV) or polysaccharide (PPV) vaccine for older adults (i.e., ≥65 y of age).2 They begin by citing two metaanalyses published in 2009 and 2013 that concluded that prevention of pneumococcal pneumonia could not be demonstrated for PPV.3,4 They overlook my earlier review of five metaanalyses that was published in 2004.5 This review showed that the study populations in prospective trials of PPV were often not representative of the populations of elderly and high-risk adults for whom PPV is recommended. Furthermore, the five metaanalyses often omitted clinical trials that should have been evaluated, included trials that should have been omitted, and frequently miscounted the numbers of subjects and outcome events in the individual clinical trials. More important, retrospective sample size calculations showed that none of the five metaanalyses included an adequate number of person years of observation to rule out false-negative results. The numbers speak for themselves and cannot be ignored. Simply put, metaanalyses of the PPV clinical trials will never tell us whether the vaccine prevents pneumococcal pneumonia or all-cause pneumonia in elderly and high-risk adults, and consequently they must be regarded as inconclusive and uninformative. Since 2004, only one small prospective clinical trial of PPV has been published (reviewed in 6). Nothing new has been added to our knowledge of PPV efficacy by the more recent metaanalyses.3,4 Epidemiologists have reminded us that the lack of evidence of PPV efficacy is not evidence of its absence. The conclusions of our earlier review still stand.5

Linezolid, an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens including multidrug-resistant staphylococci, enterococci, and pneumococci. Safety assessments were conducted for 2,046 linezolid-treated patients and 2,001 comparator drug-treated patients from seven controlled clinical trials comparing the activities of linezolid and comparator drugs against nosocomial and community-acquired pneumonia, skin and skin structure infections, and methicillin-resistant staphylococcal infections. Drug-related adverse events were primarily transient. The most frequent (≥2%) adverse events caused by linezolid and the comparator drugs were diarrhea (4.3 and 3.2%, respectively; P = 0.074), nausea (3.4 and 2.3%, respectively; P = 0.036), and headache (2.2 and 1.3%, respectively; P = 0.047). Treatment discontinuations due to drug-related events (2.4 and 1.9%, respectively), serious adverse events (11.4 and 10.6%, respectively), and deaths (4.8 and 4.9%, respectively) were similar. No clinically significant drug-related hematologic events were reported, and laboratory safety data were comparable. In the first 6 months of postmarketing surveillance, hematologic abnormalities were reported in 0.1% of linezolid-treated patients, but no irreversible blood dyscrasias were documented. The risk for transient, reversible hematologic effects from treatment with linezolid should be considered together with the clinical benefits associated with its use.

HTLV-1 infection is endemic in several Latin American countries. HTLV-1-associated myelophathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia lymphoma (ATLL) are emerging diseases in the region. Documented risk factors for acquiring the virus include breast-feeding, contaminated blood transfusion, and sexual intercourse, all of which are amenable to prevention efforts. Strongyloides stercoralis hyperinfection syndrome and therapeutic failure in apparently healthy patients with nondisseminated strongyloidiasis may be markers of HTLV-1 infection. HTLV-1 co-infection may adversely effect the clinical course of scabies and HIV disease. The new enzyme-linked immunosorbent assays (ELISA) are sensitive and specific, and Western blot technology is reliable for differentiating HTLV-1 from less common HTLV-2. HTLV-1 screening of blood donors and individuals with any disorder that suggests infection has become a necessity in Latin America to prevent the spread of this important emerging pathogen.

Among 245 cases of chronic granulomatous disease which were evaluated, fungal infection occurred in 20.4 percent. Fungi encountered include Aspergillus, Torulopsis and Candida. In 18 percent of the patients with fungal infection, the disease was limited to soft tissue or bone; all did well. Most of the patients had fungal pneumonia and/or widely disseminated disease; diagnosis was usually confirmed by open lung biopsy. Patients with pneumonia or disseminated disease who received no therapy succumbed to infection, whereas more than half the patients who received antifungal therapy were cured. Modalities of treatment included antifungal chemotherapy, surgical removal of infected tissue and granulocyte transfusion. Although several patients showed dramatic improvement during granulocyte transfusions given in combination with antifungal chemotherapy, the improvement achieved was not statistically significant when compared with that achieved with chemotherapy alone. These results emphasized the importance of phagocytic cells in defense against fungi and the need for further evaluation of granulocyte transfusion therapy in compromised hosts in whom fungal infections develop.

Normal and antibiotic-pretreated staphylococci were incubated with human neutrophils to determine the interactions between cells and antimicrobials in the killing of the organisms. Staphylococcus aureus 502A pretreated during log-phase growth with subinhibitory ((1/4) minimum inhibiting concentration) (MIC) concentrations of penicillin G were more susceptible to killing by normal neutrophils than untreated bacteria (intracellular survival 0.17+/-0.04 vs. 1.5+/-0.38%, mean+/-SEM, respectively, at 35 min in 14 experiments; P < 0.01 by t test). Furthermore, this enhanced susceptibility to killing was observed even when phagosome formation was inhibited by cytochalasin B (65.6+/-4.6% pencillintreated vs. 30.5+/-4.5% untreated killed at 30 min in 14 experiments, P < 0.001). Pretreatment of S. aureus with vancomycin similarly enhanced susceptibility to killing by cytochalasin B-treated polymorphonuclear leukocytes (PMN), whereas pretreatment with gentamicin did not. The enchancement of killing by pretreatment with cell wall-active antibiotics was present in a dose-response fashion to 1/16th the MIC. It required specific antimicrobial activity; i.e., penicillin activity was inhibited by penicillinase or by incubation with bacteria at 4 degrees C. It also required active cellular metabolism and intact neutrophils. For antibiotic-pretreated bacteria to be killed by normal and cytochalasin B-treated cells, phagocytosis or binding to the cells was essential via a serum opsonindependent mechanism. In experiments with the cytochalasin B-treated cells, all bound penicillin-treated bacteria were killed vs. only a fraction (70%) of the bound untreated bacteria. Penicillin in 10 times the MIC had no direct effects on PMN phagocytic, metabolic, or microbicidal functions against a nonsusceptible organism, Candida albicans. The results indicate a cooperative effect between cell wall-active antibiotics at low concentrations and human PMN in the killing of staphylococci. The model establishes conditions for the study of the mechanisms involved in the cooperation of these bactericidal systems.